Cellular and Molecular Biology

The role of myeloid differentiation of hematopoietic stem cells in pregnancy immunological tolerance: a systematic review

Jingxin Yao — 2024-06-05

The present research aimed to conduct a comprehensive critical analysis of existing literature, focusing on the differentiation of myeloid cells from hematopoietic stem cells within the context of immunological tolerance during pregnancy. A comprehensive systematic review was conducted by searching databases including PubMed, Scopus Biomedicine, EBSCOhost, ScienceDirect, Embase, Cochrane Library, and Web of Science. The focus was on the role of myeloid differentiation from hematopoietic stem cells in modulating immune tolerance, particularly during pregnancy and in certain disease states where they act to suppress the immune response. The quality of the evidence gathered was assessed using the GRADE rating system. Our analysis maintains objectivity and independence from the outcomes presented. The current systematic review offers a synthesis of existing research on the transformation of hematopoietic stem cells into fibroblasts across different tissue types. A thorough search of databases such as PubMed, EBSCOhost, Embase, ScienceDirect, Cochrane Library, and Web of Science was performed in conjunction with a specialist in medical information to identify original research on the derivation of fibroblasts following hematopoietic stem cell transplantation. This search yielded a total of 159 studies, of which 10 met the criteria for inclusion in this review. Reflecting on the constraints of this preliminary review, further in-depth and scientific investigations are warranted to comprehensively assess the impact of varied treatments, with a recommendation for clinicians to proceed with increased circumspection. The myeloid differentiation pathway of hematopoietic stem cells is pivotal in modulating the immune environment during pregnancy, supporting the sustenance of a healthy gestational period. Future research in this domain is expected to advance our understanding of the immunological processes occurring at the maternal-fetal boundary.

Efficacy of ozonated olive oil against peri-implant microbes isolated from peri-implantitis

Ranj Nadhim Salaie — 2024-06-05

This study aimed to investigate the antibacterial and antimicrobial activity of ozone gel against oral biofilms grown on titanium dental implant discs. The experiment used medical grade five titanium discs on which peri-implant isolated biofilms were grown. The experimental groups were control, Streptococcus mutans (S. mutans) and Granulicatella adiacens (G. adiacens), (n = 6). The oral microbes grown on titanium discs were exposed to ozone gel for 3 minutes and the antibacterial activity was assessed by turbidity test and adherence test for the antibiofilm activity test. Bacterial morphology and confluence were investigated by scanning electron microscopy (SEM), (n=3). Two bacterial species were identified from the peri-implant sample, S. mutans and G. adiacens. The results showed that adding ozone to the bacterial biofilm on titanium dental implants did not exhibit significant antibacterial activity against S. mutans. Moreover, there was no significant difference in antibiofilm activity between control and treatment groups. However, significant antibacterial and antibiofilm effect was exhibited by ozone gel against G. adiacens. Ozonated olive oil can be considered as a potential antimicrobial agent for disinfecting dental implant surfaces and treating peri-implantitis.

Genetic analysis of SARS-CoV-2 spike gene using Next Generation Sequencing from COVID-19 patients in Erbil/Iraq

Asma Ameen Ghareeb — 2024-06-05

SARS-CoV-2 has been identified by the WHO as a new virus causing mild to severe respiratory illnesses that belong to the Coronavirus family. The virus underwent rapid and continuous changes in the genetic material, especially the S gene, during COVID-19 pandemic and generated a number of new variants announced by WHO in late 2020. Mutations in the S gene have greatly affected virus pathogenesis as the spike protein is responsible for many critical processes. Delta and Omicron variants were studied extensively due to increased mortality and morbidity rates associated with their pandemic waves. This study aimed to analyse the S gene through NGS in an attempt to identify and characterize the circulating variants among the infected population in Erbil/Iraq. Nasopharyngeal and throat swab samples were collected from hospitalized and non-hospitalized patients with COVID-19 symptoms in Erbil City/Iraq from the 1^st of November 2021 to the 28^th of February 2022. Following confirmation of SARS-CoV-2 infection by RT-PCR, 15 samples were selected and sent to Intergen Lab (Ankara/Turkey) for NGS and analysis. Following analysis and alignment of the received sequences with the Wuhan-Hu-1 strain (wild-type), Delta variant was identified in 13 samples, and Omicron in two. On the whole, different mutation classes have been observed including nonsynonymous, synonymous, non-frameshift deletions and a non-frameshift insertion. The Delta-specific set of mutations, L452R, T478K and P681R, was detected in all Delta isolates. Both Omicron variants appeared to have 35 mutations. D614G variation was conserved in both variants.

Decoding LY6G6D in colorectal cancer: Unraveling biomarker potential and therapeutic insights

Mehwish Naqvi — 2024-06-05

Colorectal cancer (CRC) poses a significant global health challenge with high morbidity and mortality rates. This study investigates the role of LY6G6D, a member of the LY6/uPAR superfamily, in CRC. Employing a bioinformatic approach, we analyzed LY6G6D expression across different cancer types, compared it with known oncogenes in CRC, explored the involved genomic alterations, and assessed associated clinicopathological characteristics. LY6G6D exhibited aberrant expression, particularly elevated in CRC adenocarcinoma and highly specific to tumor tissues when compared with other oncogenes, despite its comparatively low frequency of genomic alteration. Subsequently, tumor immune infiltration analysis revealed distinct associations, primarily indicating a negative correlation, suggesting immune down-regulation. Survival analysis in context of LY6G6D was conducted with Kaplan-Meier (KM) curves, indicating a 10% risk of disease recurrence in the case of elevated expression. Additionally, we constructed a 3D protein model of LY6G6D through ab-inito approach. The protein model was validated, followed by conservation analysis and active site identification. Active site identification of LY6G6D’s final predicted model revealed some similar sites that were estimated to be conserved. Target-guided drug molecules were collected and molecular docking was executed, proposing Cardigin (Digitoxin) and Manzamine A as potential therapeutic candidates. In conclusion, LY6G6D emerges as a significant biomarker for diagnostic and therapeutic applications in CRC, highlighting its multifaceted role in tumorigenesis. The proposed drugs present avenues for further investigations.

Experimental study of slow-released Angiogenin by silicon micro-needle in improving blood support to multiple-territory perforator flaps in rats

Xiaojun Liu — 2024-06-05

This research aimed to investigate the effect of slow-released angiogenin by silicon micro-needle on angiogenesis in the Choke zone of dorsal multiple-territory perforator flap in rats, as well as its mechanism. Thirty-six adult Sprague-Dawley (SD) rats were randomly divided into control group, model group, and four experimental groups. In model group, slow-release saline through a silicon micro-needle was placed in choke II zone of the flap 7 days before the operation. For rats in four experimental groups, angiogenin was released via micro-needle in the choke I and choke II zones of the cross-zone flap 7 days before and 3 days before flap surgery, respectively. A 12 cm × 3 cm cross-zone perforator flap model was made on the back of all five groups. The flap survival rate in slow-release angiopoietin group was statistically higher than that in model group (P<0.05). Angiogenin in choke zone of the flap was increased in slow-release angiogenin group (P<0.05). In slow-release angiogenin group, the micro-vessel density was increased and the arteriovenous diameter was decreased, while the arteriovenous diameter was increased in model group (P<0.05). The levels of vascular endothelial growth factor A (VEGF-A) and angiotensin 1 (ANG-1) in choke zone were both elevated in slow-release angiogenin group (P<0.05). The expression of CD31 was significantly elevated in flaps of experimental groups (P<0.05). Micro-needle to slow release Angiogenin can increase the drug concentration in the tissues of the choke zone, promote the vascularization of rat dorsal crossover area perforator flap, reduce the possibility of flap ischemic necrosis, and improve the flap survival rate.

Isolation and characterization of piceatannol producing bacteria from soil in Erzurum, Turkey

Taha Yasin Koc — 2024-06-05

Piceatannol, resveratrol's derivative, and a valuable polyphenol has managed to become one of the most remarkable candidate molecules for drug development research, with its high bioactive properties and higher stability. On the other hand, the very low amount of piceatannol in plants which are its natural source increases the cost and limits the commercialization possibilities of the product. To overcome this bottleneck, a limited number of studies have recently shown that it is possible to produce piceatannol from the resveratrol precursor much cheaper by regioselective hydroxylation catalyzed by bacteria isolated from the soil, and the search for new bacteria of similar nature in new ecosystems has gained popularity. The aim of our study, which was prepared within this framework, is the bacterial isolate with regioselective hydroxylation potential obtained as a result of selective isolation steps; determination of resveratrol hydroxylation potentials and piceatannol product yields, investigation of possibilities to increase piceatannol yield with optimization trials and identification of isolates with the highest yield. For this purpose, 200 bacterial isolates capable of resveratrol hydroxylation were obtained from soil samples taken from Erzurum (Turkey) and its surroundings by using selective media. In the continuation of the study; resveratrol hydroxylation trials were carried out with these isolates and 55 active isolates capable of producing piceatannol by regioselective hydroxylation were selected. Then, yield improvement studies of active isolates were carried out by using different carbon sources and optimizing the culture conditions. As a result, a culture collection was created by identifying the 6 most active bacterial isolates with commercialization potential using conventional and molecular methods. These are 4 Gram-positive (Rhodococcus sp., Rhodococcus erythropolis, Paeniglutamicibacter sp., Arthrobacter sp.) and 2 Gram-negative (Shinella sp., Ensifer adhaerens) bacterial isolates. As a result of the optimization studies, three of these isolates used phenol as a biocatalyst, while the other three increased the production yield of piceatannol by using 4-hydroxyphenylacetic acid.

The application of DPE, CSEA, and EA in labor analgesia for nulliparous women and their impact on maternal and infant safety

Kai Kang — 2024-06-05

This work compared the effects of dural puncture epidural (DPE), combined spinal epidural analgesia (CSEA) and epidural analgesia (EA) on labor analgesia for primiparae and their impacts on maternal and infant safety. A total of 204 primiparae in need of labor analgesia for vaginal delivery were allocated to DPE, CSEA and EA groups. At 10 min, 30 min and 1 h after analgesia, the DPE and CSEA groups showed lower VAS scores and quicker onset of action than EA group. There was no significant difference in the duration of analgesia and labor and fetal decelerations among the 3 groups. At 1 min and 5 min after childbirth, the neonatal Apgar scores showed no significant difference between the 3 groups. The Bromage scores of DPE and EA groups were lower than those of CSEA group. The incidence of pruritus, hypotension, and postpartum headache in DPE and EA groups were lower than those in CSEA group. To sum up, the efficacy of DPE in labor analgesia for primiparae is similar to that of CSEA, with no obvious effect on labor stage and neonatal Apgar score, no additional complications and less LLMB, pruritus, hypotension and postpartum headache.

LINC01133 contributes to the malignant phenotypes of non-small cell lung cancer by targeting miR-30b-5p/FOXA1 pathway

Xiangbing Xin — 2024-06-05

This study aimed to explore the mechanism of action of LINC01133 in non-small cell lung cancer. LINC01133 expression in NSCLC patient tissues and cells was detected by qRT-PCR. After transfecting siRNA-LINC01133 in NSCLC cells, the proliferation and invasive migration ability of the cells were assessed via CCK-8 and Transwell assay, respectively. The sublocalization of LINC01133 in NSCLC cells was analyzed by bioinformatics prediction and nucleoplasm separation assay and RNA-FISH assay. Analysis of the binding relationship between LINC01133, FOXA1 and miR-30b-5p was all through bioinformatics website analysis, dual-luciferase reporter and RNA Pulldown assay. Functional rescue experiments confirmed the character of miR-30b-5p and FOXA1 in LINC01133 regulating the NSCLC cells biological behavior. LINC01133 high expressions were found in NSCLC tissues and cells. siRNA-LINC01133 treatment inhibited NSCLC cells malignant behavior. Mechanistically: LINC01133 promoted FOXA1 expression through adsorption binding of miR-30b-5p. Knocking down miR-30b-5p expression or up-regulating FOXA1 expression was able to reverse siRNA-LINC01133 inhibitory effect of tumor cell malignant behavior. LINC01133 promoted FOX1 expression by competitively binding miR-30b-5p, which attenuated the targeting inhibitory effect of miR-30b-5p on FOXA1 and ultimately promoted proliferation and invasive migration of NSCLC cells.

Maternal and filial consumption of probiotics protects from acute stress-induced anxiety and loss of benevolent gut microbes

Abdulazeez Kadhim Wali — 2024-06-05

The study aimed to determine the effects of probiotic consumption during pregnancy and lactation and post-weaning on acute stress-induced anxiety and gut beneficial microbiota of the female offspring mice.The female offspring mice were divided into several groups: intact, control (only stressed), PBS/dam (dams gavaged with PBS), PRO/dam (dams gavaged with probiotics), PRO/dam+off (both dams and offspring gavaged with probiotics), and PBS/dam+off (both dams and offspring gavaged with PBS)The probiotics chosen are mainly L. rhamnosus, B.breve, and B. longum (108 CFU/ml). Foot shock stress will be applied for one hour on the 43^rd day after birth. Behavioral tests were conducted using the open field and elevated plus-maze. Corticosterone was measured by ELISA kit, and intestinal microflora with qPCR.The data showed that PRO/dam+off had more entries into open arms compared to the control group and decreased move distance and time spent in closed arms compared to the control group. However, there was no significant difference between the PRO/dam group and the control group. In the open field test, the control group spent less time in the inner zone compared to the intact group and in PRO/dam+off group. Corticosterone hormone was increased in the control group and was decreased in the PRO/dam+off. Bifidobacteria and Lactobacilli decreased in the control group in comparison to the intact group, and in the PRO/dam+off group increased compared with other groups. Maternal and filial supplementation with a multi-strain probiotic mixture increased levels of beneficial bacteria and reduced stress-induced anxiety in mice.

LINC00472 suppresses non-small cell lung cancer progression via regulating miR-23a-3p/CCL22 axis

Sanhu Yang — 2024-06-05

Long non-coding RNA (lncRNA) LINC00472 has a close connection with the development of tumors. The aim was to explore the role of LINC00472 on NSCLC cell biological function in vivo and its potential mechanisms. The mRNA levels of LncRNA 00472 and microRNA-23a-3p, were determined by RT-qPCR. Cell Counting Kit-8, cell scratches and western blot assays were used to analyze the proliferation, migration and level of apoptosis-associated proteins. Luciferase reporter assay validates the binding between LINC00472/CCL22 and miR-23a-3p. LINC00472 and CCL22 were lowly expressed in NSCLC tissues and cells, while miR-23a-3p expression was upregulated. LINC00472 overexpression significantly depressed NSCLC cell cellular behavior, whereas promoting cell death. MiR-23a-3p could reverse these above-mentioned biological behavior changes caused by LINC00472 overexpression. Additionally, LINC00472 increased CCL22 expression through sponging miR-23a-3p. Knocking down CCL22 antagonized the inhibitory effect of LINC00472 on NSCLC cell survival. LINC00472 may reduce the cellular growth, and accelerate death of NSCLC through increasing CCL22 expression by targeting miR-23a-3p.

The effect of external fixator on bone metabolism in patients with open fracture of extremities

Yu Shi — 2024-06-05

This experiment aimed to explore the influence mechanism of external fixator on open fracture. A total of 128 patients with open tibiofibular fractures were included in this study. The patients were randomly divided into external fixator group (n=64) and control group (n=64) according to the order of admission. Double-blind controlled observation was used. The levels of osteocalcin (BGP), β-CTX, P1 NP, BALP, including haptoglobin (Hp), ceruloplasmin (CER), serum adrenocorticotropic hormone (ACTH), cortisol (COR), C-reactive protein (CRP), white blood cell (WBC) and interleukin-6 (IL-6) were recorded in different groups. The postoperative VAS score and quality of life were recorded. Log-rank was used to analyze the difference in postoperative adverse reaction rates among different groups. External fixation stent treatment increased BGP, PINP, and BALP expression and decreased β-CTX, Hp, CER, ACTH, COR, CRP, WBC, and IL-6 levels. Patients in the external fixation stent group had significantly lower VAS score quality of life scores and incidence of adverse events than the control group. External fixation stents protect open fracture patients by promoting bone metabolism.

Mechanism of the effect of TREM2 on cognitive function in autistic mice

Yi Tian — 2024-06-05

This study aimed to investigate the mechanism of the effect of TREM2 on cognitive function in autistic mice. TREM2 overexpression and knockdown viruses were given to autism spectrum disorder (ASD) mice and BV2 microglia cell line. To assess cognitive performance, all groups of mice took part in the open field, new object recognition, Morris water maze, and three-box social experiments. Double immunofluorescence labeling demonstrated co-localization of LC3II and NeuN. Proteins from the PI3K/Akt/mTOR pathway were identified. In vivo, behavior studies revealed that TREM2 could successfully improve ASD mice’s social interaction and cognitive performance. Besides, we discovered that TREM2 could increase autophagy in ASD mice. In vitro, overexpressing TREM2 reduced the expression of PI3K/AKT/mTOR pathway proteins, whereas knocking down TREM2 increased the expression of PI3K/AKT/mTOR pathway proteins. In conclusion, TREM2 could inhibit PI3K/Akt/mTOR signaling pathway, enhance autophagy, and improve the social communication ability and cognitive function of ASD mice.

Glucocorticoids promote joint microenvironment alteration of GABBR1 expression associated with mitigating rheumatoid arthritis

Shilong Song — 2024-06-05

GABBR1 receptors have been implicated in the progression of rheumatoid arthritis (RA), and p38 MAP kinase (MAPK) was shown to be downregulated by GABA and result in unchecked production of pro-inflammatory cytokine. GABBR1 is a member of GABA receptors, and it is known to be upregulated and plays a vital role in RA. Glucocorticoids are efficient therapeutics in rheumatoid arthritis (RA) and are known to regulate GABA actions; therefore, we intended to investigate the potential of glucocorticoids in RA concerning the potential pathway GABBR1/MAPK. Joint specimens were obtained from collagen-induced arthritis mouse model. A double-blind semi-quantitative analysis of vascularity, cell infiltration, as well as lining thickness by help of a 4-point scale setting was used to assess joint inflammation. Expression of GABBR1 and p38 was evaluated immunohistochemically. In vitro peripheral blood (PB), synovial fluid (SF), and mononuclear cells (MCs) were acquired from RA mice. Western blotting was used for detecting expression of GABBR1 and p38 proteins. The presence of high levels of GABBR1 and p38 was prevalent in RA joints relative to healthy joints and related to the inflammation level. Glucocorticoid treatment alters GABBR1 along with p38 protein expression in joints while reducing joint inflammation. Ex vivo and in vitro assays revealed glucocorticoids have a direct impact on p38, such as the decreased GABBR1 expression level after dexamethasone incubation with SFMC. GABBR1 together with p38 expression in RA joints depends on local inflammation and can be targeted by glucocorticoids.

M2 macrophages regulate KDM6B/PFKFB2 metabolic reprogramming of cervical squamous cell carcinoma through CXCL1

Jing Yu — 2024-06-05

Macrophages in the tumor microenvironment can polarize into M1 or M2 forms, with M2 macrophages (M2φ) promoting tumor growth and metastasis in cervical squamous cell carcinoma (CESC). This study explored the effects of M2φ on CESC metabolic reprogramming both in vitro and in vivo. Results showed that M2φ secreted CXCL1, which significantly increased CESC migration and metabolic regulation. Further experiments revealed that CXCL1 upregulated KDM6B to enhance PFKFB2 transcriptional activity, thus regulating CESC glucose metabolism. Transcriptome sequencing screened 5 upregulated genes related to glycolysis, with PFKFB2 showing the most significant increase in cells treated with rCXCL1. Dual-luciferase reporter assay confirmed that rCXCL1 enhances PFKFB2 transcriptional activity. Bioinformatics analysis revealed a high correlation between expressions of KDM6B and PFKFB2 in CESC. Mechanistic experiments demonstrated that KDM6B inhibited H3K27me3 modification to activate PFKFB2 transcriptional expression. In conclusion, M2φ secreted CXCL1 to promote CESC cell migration and invasion, and CXCL1 activated KDM6B expression in CESC cells, inhibiting H3K27 protein methylation modification, and enhanced PFKFB2 transcriptional activity to regulate CESC glucose metabolism. These results provided new insights into the complex interplay between the immune system and cancer metabolism, which may have broader implications for understanding and treating other types of cancer.

The combination of tetramethylpyrazine and vitamin A acid in the treatment of skin photoaging by activating the HIF-1α pathway

Weijun Chen — 2024-06-05

Skin photoaging is a skin degenerative disease that causes patients to develop malignant tumors. The existing clinical treatment of photoaging has limitations. This greatly reduces the recovery rate of photoaging patients. Studies have confirmed that Ligusticum wallichii Franch (LWF) monomer tetramethylpyrazine (TMP) alleviates various skin diseases. The combination of traditional Chinese medicine and Western medicine helps with this process. Our research aimed to explore the specific treatment mode and molecular mechanism of TMP in treating skin photoaging. CCK-8 assays were used to evaluate the activity and toxicity of HaCaT cells. β-galactosidase aging, Carbonyl compound and nitrosylated tyrosine assays were used to analyze the aging of HaCaT cells. ROS assays and ELISA were used to analyze the enrichment of ROS. The molecular docking experiment analyzed the binding of TMP and HIF-1α. qRT-PCR and Western blot were used to detect the activation of skin aging-related pathways. HE staining was used to analyze the thickness of the stratum corneum skin on the back skin of mice. 200μg/L LWF alleviates cellular photoaging and mouse skin photoaging by reducing ROS enrichment. Its monomer TMP plays an important role in this process. The combination of TMP and HIF-1α accelerates the degradation of ROS by activating the Nrf2/ARE signaling pathway. This process reduces the apoptosis of cells damaged by light. In addition, we also found that the combination of TMP and retinoic acid (RA) is more beneficial for the treatment of skin damage caused by light in mice. The combination therapy of TMP and RA alleviates skin oxidative stress response through overexpression of HIF-1α. This plan is beneficial for the treatment of skin photoaging.

The impact of laparoscopic radical gastrectomy on the inflammatory response and immune function of patients with gastric cancer

Jie Ling — 2024-06-05

The currest study aimed to measure the effects of laparoscopic radical gastrectomy on inflammatory response along with immune function in gastric cancer (GC) patients. Seventy patients with GC in our hospital were retrospectively chosen to be the study objects and separated into control group (CG, 35 cases) and observation group (OG, 35 cases). Patients in the OG received radical laparotomy. Patients in the OG received laparoscopic radical gastrectomy. The surgical indicators, postoperative recovery indicators, inflammatory factors, immune function, incidence of adverse reactions along with quality of life of patients in both groups were compared. In contrast to the CG, the operation time of the OG presented as shorter (P<0.05), and the amount of intraoperative blood loss together with postoperative VAS score in the OG presented lower (P<0.05), but the number of lymph nodes dissection presented not statistically significant between 2 groups (P>0.05). The postoperative exhaust time, feeding time as well as hospital stay in the OG presented shorter relative to the CG (P<0.05). The serum levels of CRP, and IL-6 together with TNF-α presented elevated in both groups after surgery, and those in the OG presented lower when compared with the CG (P<0.05). The serum levels of IgA, and IgG together with IgM presented declined in both groups after surgery, and those in the OG presented higher when compared with the CG (P<0.05). The incidence of postoperative complications in the OG presented reduction relative to the CG (P<0.05). The GLQI scores of the OG presented significantly higher relative to the CG at discharge (P<0.05). Compared with radical gastrectomy, laparoscopic radical gastrectomy is more suitable for the treatment of GC, which can reduce the inflammatory response and promote the immune function of GC patients.

In-silico and in-vitro studies revealed alpha-amyrin as a potent pnhibitor of TLR2 for the therapeutics of bacterial infection and sepsis

Thoraya A- Elgadir — 2024-06-05

This study employed a multifaceted approach to investigate the inhibitory potential of alpha-amyrin against TLR2, a key player in bacterial infection and sepsis. A high-resolution TLR2 model was constructed using Swiss-MODEL, exhibiting excellent quality with 100% sequence identity and coverage. Cavity detection revealed five significant cavities on TLR2. Molecular docking identifies alpha-amyrin as a potent inhibitor, displaying a strong binding affinity of -8.6 kcal/mol. Comprehensive analyses, including ADMET predictions, PASS analysis, and SwissTargetPrediction, affirm alpha-amyrin's drug-like properties and diverse biological activities. Cytotoxicity assays on HEK-293 cells confirm its safety, and fluorescence-based inhibition assays provide empirical evidence of its inhibitory potency on TLR2 enzymatic activity. Further validations in HUVECs show a significant decrease in TLR2 mRNA expression (p<0.01) and activity (p<0.05) upon alpha-amyrin treatment. In conclusion, this integrative study positions alpha-amyrin as a promising therapeutic candidate for TLR2 inhibition, emphasizing its potential in combating bacterial infections with safety and efficacy.

Oridonin represses lung cancer cell proliferation and migration by modulating AFAP1-AS1/IGF2BP1

Min Chen — 2024-06-05

Oridonin belongs to a small molecule from the Chinese herb Rabdosia rubescens with potent anticancer activity. In spite of the lncRNA AFAP1-AS1 has been proven to exert promoting function in lung cancer, its relationship with oridonin in lung cancer is obscure. Therefore, our study planned to explore the potential of oridonin in lung cancer as well as unveil the regulatory mechanism of oridonin on AFAP1-AS1 in lung cancer cells. In the present study, oridonin inhibited lung cancer cell proliferation, migration, as well as invasion, as evidenced by MTT, wound healing, as well as transwell assays. Besides, we observed that oridonin could downregulate AFAP1-AS1 expression, and overexpressed AFAP1-AS1 could reverse the repressive effects of oridonin on lung cancer cell proliferation, migration, as well as invasion. More importantly, we found that AFAP1-AS1 could bind to IGF2BP1 through starBase prediction and RIP assay. The expression level of IGF2BP1 was also reduced by oridonin treatment but reversed after AFAP1-AS1 overexpression. Additionally, we proved that overexpressed IGF2BP1 could reverse the repressive impacts of oridonin on lung cancer cell proliferation, migration, as well as invasion. Further, in vivo experiments validated the repressive role of oridonin on tumor growth of lung cancer. Together, oridonin inhibits lung cancer cell proliferation as well as migration by modulating AFAP1-AS1/IGF2BP1, and AFAP1-AS1/IGF2BP1 possesses the potential to be a promising therapy targeting for lung cancer, especially in oridonin treatment.

Exploration of mitochondrial autophagy related genes in the diagnosis model construction and molecular marker mining of Alzheimer's disease based on multi-omics integration

Shan Wang — 2024-06-05

Key features of Alzheimer's disease include neuronal loss, accumulation of beta-amyloid plaques, and formation of neurofibrillary tangles. These changes are due in part to abnormal protein metabolism, particularly the accumulation of amyloid beta. Mitochondria are the energy production centers within cells and are also the main source of oxidative stress. In AD, mitochondrial function is impaired, leading to increased oxidative stress and the production of more reactive oxidative substances, further damaging cells. Mitophagy is an important mechanism for maintaining mitochondrial health, helping to clear damaged mitochondria, prevent the spread of oxidative stress, and reduce abnormal protein aggregation. To this end, this article conducts an integrated analysis based on DNA methylation and transcriptome data of AD. After taking the intersection of the genes where the differential methylation sites are located and the differential genes, machine learning methods were used to build an AD diagnostic model. This article screened five diagnostic genes ATG12, CSNK2A2, CSNK2B, MFN1 and PGAM5 and conducted experimental verification. The diagnostic genes discovered and the diagnostic model constructed in this article can provide reference for the development of clinical diagnostic models for AD.

MicroR-1199-5p targeting SRD5A2 promotes the biological behavior and EMT of hypospadias cells

Yifu Chen — 2024-06-05

Hypospadias, an oft-occurring penis anomaly, ranks among neonatal's foremost birth defects. The SRD5A2 can affect male reproductive system development and is abnormally expressed in its epithelial cells. This study exploration aimed at understanding the role of SRD5A2 in the development of hypospadias from a molecular perspective. SRD5A2 levels in hypospadias primary cells were analyzed by Western blot, while targeted interaction with miR-1199-5p was ascertained by dual-luciferase gene reporter assay. In vitro biological experiments were used to confirm the biological function of SRD5A2 in hypospadias. SRD5A2 expression was significantly upregulated, and miR-1199-5p expression was significantly downregulated in hypospadias primary cells. Intervention of SRD5A2 expression can affect cell proliferation, migration, invasion, EMT, and the expression of cell cycle-related proteins. Additionally, we found that SRD5A2 is regulated by upstream miR-1199-5p and can enhance the effect of SRD5A2 on hypospadias cells. Conclusions Silencing SRD5A2 promotes cell proliferation, invasion, and migration blocks the cell cycle at the G1 phase, and simultaneously promotes EMT, cell cycle, and cell proliferation-related protein expression. The biological function of SRD5A2 in hypospadias cells is regulated by miR-1199-5p. SRD5A2 may be an effective therapeutic target for hypospadias.

Immunohistochemical co-expression of PAX2 and CAIX predicts better prognosis in clear cell renal cell carcinoma after nephrectomy: A retrospective observational study

Honggang Shao — 2024-06-05

Clear cell renal cell carcinoma (ccRCC) is a lethal malignancy with high metastatic probability. Paired box 2 gene product (PAX2) carbonic anhydrase IX were biomolecules closely linked with ccRCC development and outcomes of multiple malignancies. We aim to explore the role of immunohistochemical staining of PAX2 and CAIX to predict ccRCC prognosis after nephrectomy. Surgical specimens of patients who were pathologically diagnosed as ccRCC were reviewed. Expression levels of PAX2 and CAIX were assessed via immunohistochemical staining. Recurrence-free survival (RFS) and overall survival were compared among different phenotypes. Inverse probability of treatment weighting (IPTW) was used for adjustment of confounding factors. 56 patients were included. Patients with PAX2 and CAIX high-expression (the two-high group, n=8) had significantly longer RFS and OS than those of simultaneously down-expression (the two-low group, n=31). Median RFS was 38.4 (95% CI: 32.3-NA) for the two-high group and 14.8 (95% CI: 13.4-39.0) months for the two-low group (P=0.043). IPTW confirmed PAX2 and CAIX co-expression is associated with less recurrence risk HR: 0.39, 95% CI: 0.17-0.92, P=0.031). Co-expression of PAX2 and CAIX is associated better prognosis of ccRCC. We are looking for validation by large cohort studies.

Human dental pulp stem cells differentiation into odontoblast and osteoblast-like cells on scaffolds contain bioactive materials

Ganjo Ghawtha Khudhur — 2024-06-05

Epigenetic change has been found to play an important role in cell differentiation and regulation and the dental pulp stem cell in tissue engineering is gaining attention due to the ability of cells to differentiate into odontoblast and other cells. This study evaluated the influence of poly L- lactic acid with hydroxyapatite-coated with polyaniline scaffold (PLLA/HA/PANI) on dental pulp stem cell (DPSC) proliferation and differentiation. After scaffold preparation and DPSCs seeding, the cells proliferation and differentiation were evaluated by immunocytochemistry assay and cell viability was measured by cytotoxicity / MTT assay. The results showed (PLLA/HA/PANI) scaffold facilitates DPSC proliferation and differentiation with gene expression. This finding underscores the promise of this biomaterial combination as a scaffold for dental tissue regeneration and application.

Prevalence of gallbladder cancer in cholecystectomized patients in Sulaymaniyah city

Deari A. Ismaeil — 2024-06-05

Gallbladder cancers (GBC) are rare, and they are one of lethal neoplasms of biliary system. The diagnosis is either incidentally during histopathological examinations after cholecystectomy or due to complications of local or systemic spread of the malignancy. The incidence differs ethnically and geographically. The aim was to identify increase risk of cancer in the Kurdistan region by searching for the number of GBC cases among cholecystectomy patients in Sulaymaniyah governorate. This study is laboratory-based retrospective study, including data obtained from 8315 cholecystectomized patients in Sulaymaniyah governorate from 2017- 2021. The information within the questionnaire included: age, sex, clinical notes and histopathological findings; including GBC. The total of 8315 cases; were 2149 males (25.8%) and 6166 females (74.2%). The mean age was (44.67+/-15.18) years. Forty-five cases have been reported as adenocarcinoma of GB and one case of Carcinosarcoma. Among the patients, 875 cases (10.50%) had acute cholecystitis. A significant relationship was found between the findings and the age and gender of the patients. GBC is not common and is mainly diagnosed incidentally after routine post-operative histopathological examination, and mainly affects old ages.

The effect of vitamin E incorporated into injectable platelet-rich fibrin on orthodontic tooth movement in rabbits

Mahmoud Kanan Mohsin — 2024-06-05

To evaluate the effects of injectable platelet fibrin (iPRF) and combined vitamin E-iPRF on orthodontic tooth
movement (OTM) rates in rabbits, 35 male New Zealand white rabbits were involved in this study using splitmouth
design. OTM was carried out on the mandibular first premolar using 100g nickel titanium closing coil.
Right side served as study group, isolated iPRF in one group and combined vitamin E-iPRF in other group
was injected buccally and lingually (iPRF group, Vit E-iPRF group), and left side acted as positive control
group (CG) by injecting normal saline (positive CG). The rate of OTM was measured using intra-oral scanner
on days 7,14 and 21. Histological and Micro CT scan were examined on days 0, 7, 14 and 21. The iPRF and
combined Vitamin E-iPRF demonstrated significant greater rate of OTM on days 7 and 14 in comparison to
control group, only significant differences between iPRF and combined vitamin E-iPRF were seen on day 14.
In all time intervals as compared to the CG, the number of osteoclasts was significantly higher in the isolated
iPRF and combined vitamin E-iPRF groups. Significant reduction in bone volume fraction (BV/TV) was
demonstrated in iPRF and combined vitamin E-iPRF groups in all time points, however, non-significant differences
were found in trabecular thickness (Tb.Th) and trabecullar separation (Tb.Sp). Local injection of iPRF
and combined vitamin E-iPRF showed temporary increase in the rate of OTM.

Evaluation of temporomandibular joint morphology and morphometry in male osteoporotic patients using advanced imaging and biochemical markers: A cross-sectional study

Shara Mustafa H. Kareem — 2024-06-05

Osteoporosis is a condition with reduced bone mass and disrupted architecture. Osteoporosis affects the Temporomandibular disorders (TMD) by changing bone density and quality. This study aims to determine the nature and extent of temporomandibular joint (TMJ) involvement in osteoporotic patients by correlating TMJ morphological changes detected by CBCT with systemic bone health indicated by BMD T-scores from DEXA and analyzing BTMs in serum and saliva. This study was a cross-sectional study conducted from May 2021 to December 2022. It involved 50 participants divided into two groups (N=25). One group was healthy male, while the other group had osteoporosis male. Saliva and blood samples were collected, and diagnostic imaging was conducted. The prevalence of various bone changes in the condyle was examined using CBCT. Erosion was found to be the most common, followed by Flattening, Osteophyte, and Subchondral cysts. The study group had significantly higher rates of smooth condyle, erosive lesions, and osteophytes compared to the control group. Pseudocyst decreased on the right side but increased on the left side. Pain on the right side increased more in the study group, and the T score for osteoporosis was higher in the study group. Joint spaces, condyle diameter, and glenoid cavity measurements differed significantly between sick and healthy people, as shown by CBCT (P≤0.001). Only the ALP parameter in the serum showed a significant increase in the study group compared to the control group. Saliva analysis revealed higher levels of calcium, osteocalcin, and ALP in the case group compared to the control group. The results of this study showed that CBCT as a specialized technique in imaging by providing detailed images can be used to evaluate osteoporosis and be used as an accurate diagnostic tool.

The efficacy of Bortezomib-based regimens on survival state in newly diagnosed multiple myeloma patients

Kawa Muhamedamin Hasan — 2024-06-05

The prognosis of patients with multiple myeloma (MM) has significantly improved over the past ten years because of several innovative treatments, including the proteasome inhibitor Bortezomib and immunomodulatory drugs (IMiDs) like Thalidomide and Lenalidomide. The present study aimed to determine the effectiveness of Bortezomib-based regimens on survival state of MM patients. This retrospective study included 204 newly diagnosed MM patients who were registered at Nanakali Hospital for Blood Diseases and Cancer, Erbil- Iraq, between April 2008 and April 2022. The patients were split into two primary groups: those receiving treatment with Bortezomib and those not. Clinical and laboratory data, treatment type, responsiveness to induction therapy, and survival results were examined in the enrolled patients' medical records. The mean patient age was 60 years, males constituted 55.8% of the included patients. At the time of diagnosis, 98 individuals (48%) had stage 3 illness. Except for the LDH, which was noticeably higher in the non-Bortezomib group, the patients laboratory results did not substantially change between the Bortezomib and non-Bortezomib groups (p = 0.001). In patients treated with Bortezomib, the complete response (CR) rate following induction was substantially greater (35.2%) than in those treated without Bortezomib (9.1%). Compared to the non-Bortezomib group, the median survival time of the Bortezomib group was considerably greater (p < 0.001). Bortezomib has a significant role in inducing a CR before bone marrow (BM) transplantation, and it has a significant role in the survival outcome in MM.

Regulation and molecular mechanism of adiponectin on the proliferation, apoptosis, autophagy, and chemosensitivity of LN18 Glioma cell line

Peng Sun — 2024-06-05

This study aimed to explore the regulatory effects and associated mechanisms of adiponectin on apoptosis and proliferation in the LN18 glioma cell line through the AMPK and Akt signaling pathways. Additionally, we sought to elucidate the impact of adiponectin on the chemosensitivity of the LN18 glioma cell line to temozolomide (TMZ). The proliferation rate of glioma cells treated with adiponectin was assessed using the cholecystokinin (CCK8) assay. The Western blot analysis was employed to assess the expression of p-Akt, p-AMPK, p-mTOR, cleaved caspase3, Bax, Cyclin D1, and Cyclin B1 following adiponectin treatment. Cell apoptosis was quantified using AnnexinV/PI flow cytometry, while changes in the cell cycle were detected using PI staining flow cytometry. The findings revealed that adiponectin upregulates p-AMPK expression and downregulates p-mTOR expression in the PTEN wild-type glioma cell line LN18, with no discernible effect on p-Akt expression. Moreover, adiponectin inhibits the proliferation rate of the PTEN wild-type glioma cell line LN18, enhances the expression of cleaved caspase3 and Bax, and significantly elevates the apoptosis rate, as evidenced by AnnexinV/PI flow cytometry. Adiponectin was observed to suppress the expression of Cyclin D1 and Cyclin B1, increase the number of cells in the G1 phase, and promote autophagy. Additionally, adiponectin augments the expression of Beclin1 and the ratio of LC3II/I in the PTEN wild-type glioma cell line LN18, while decreasing p62 expression. In conclusion, this study posits that adiponectin holds therapeutic promise for glioma treatment. Furthermore, adiponectin enhances the inhibitory effect of TMZ on the proliferation rate of LN18 cells when treated with 0.1 mM and 1 mM TMZ. These results collectively suggest that adiponectin impedes proliferation, encourages apoptosis and autophagy in the LN18 glioma cell line, and heightens its sensitivity to the chemotherapeutic drug TMZ.

LINC00520 promotes colorectal cancer progression through miRNA-195-3p / NAT2 axis

Haibin Liu — 2024-06-05

In this study, we investigated the role of LINC00520 in colorectal cancer (CRC) progression. We analyzed LINC00520 expression in 15 pairs of CRC tissues and adjacent tissues using qRT-PCR, revealing significantly elevated levels in CRC tissues and cell lines. Lentivirus-mediated up/down-regulation of LINC00520 in CRC cell lines demonstrated that increased LINC00520 expression enhanced cell invasiveness, as confirmed by transwell and wound healing assays. Bioinformatics analysis identified a regulatory axis involving LINC00520, microRNA-195-3p, and NAT2. Luciferase assays confirmed direct binding between LINC00520 and microRNA-195-3p, as well as microRNA-195-3p and NAT2. Overexpression of NAT2 reversed the inhibitory effects on invasion and migration induced by LINC00520 silencing. This suggests that LINC00520, highly expressed in CRC tissues, may modulate tumor biological functions through the microRNA-195-3p/NAT2 axis. Our findings provide insights into the mechanism underlying CRC progression, highlighting the potential of LINC00520 as a therapeutic target.

Andrographolide influences IDD cell autophagy and oxidative stress under mechanical pressure via miR-9/FoxO3/PINK1/Parkin molecular axis

Jianwei Liu — 2024-06-05

Intervertebral disc degeneration (IDD) is characterized by the decreased function and number of nucleus pulposus cells (NPCs) caused by excessive intervertebral disc (IVD) pressure. This research aims to provide novel insights into IDD prevention and treatment by clarifying the effect of andrographolide (ANDR) on IDD cell autophagy and oxidative stress under mechanical stress. Human primary NPCs were extracted from the nucleus pulposus tissue of non-IDD trauma patients. An IDD cell model was established by posing mechanical traction on NPCs. Through the construction of an IDD rat model, the influence of ANDR on IDD pathological changes was explored in vivo. The proliferation and autophagy of NPCs were decreased while the apoptosis rate and oxidative stress reaction were increased by mechanical traction. ANDR intervention obviously alleviated this situation. MiR-9 showed upregulated expression in IDD cell model, while FoxO3 and PINK1/Parkin were downregulated. Decreased proliferation and autophagy as well as enhanced apoptosis and oxidative stress response of NPCs were observed following miR-9 mimics and H89 intervention, while the opposite trend was observed after FoxO3 overexpression. FoxO3 is a direct target downstream miR-9. The in vivo experiments revealed that after ANDR intervention, the number of apoptotic cells in rat IVD tissue decreased and the autophagy increased. In conclusion, ANDR improves NPC proliferation, and autophagy, inhibits apoptosis and oxidative stress, and alleviates the pathological changes of IDD via the miR-9/FoxO3/PINK1/Parkin axis, which may be a new and effective treatment for IDD in the future.

In vivo and in vitro studies on the role of regulating Smac expression in the occurrence and development of colon cancer

Donglei Zhang — 2024-06-05

We aimed to explore the role of regulating Smac expression levels in the occurrence and development of colon cancer through in vitro and in vivo experiments. Colon cancer cells HT-29 were cultured and transfected into different groups. qRT-PCR was used to detect the expression level of Smac in cells; Flow cytometry was used to detect the apoptotic ability of each group of cells; Western blot was used to detect the protein expression of Smac and apoptosis-related factors Survivin and Caspase-3; The nude mouse tumorigenesis experiment was conducted to detect the regulatory effect of regulating Smac expression levels on the growth of colon cancer transplanted tumors in vivo. In comparison to the FHC group, the HT-29 group exhibited a decrease in Smac expression. The si-Smac group, when compared with the si-NC group, showed significant reductions in Smac mRNA and protein levels, weaker cell apoptosis, increased Survivin, and decreased Caspase-3 expression. Contrarily, the oe-Smac group, against the oe-NC group, displayed increased Smac mRNA and protein levels, enhanced apoptosis, reduced Survivin, and elevated Caspase-3 expression. In nude mice tumor transplantation experiments, the LV-sh-Smac group, as opposed to the LV-sh-NC group, had tumors with greater volume and weight, reduced Smac and Caspase-3, and increased Survivin expression. In contrast, the LV-oe-Smac group, compared with the LV-oe-NC group, showed tumors with decreased volume and mass, increased expressions of Smac and Caspase-3, and decreased Survivin. Smac is lowly expressed in colon cancer. Upregulation of Smac expression can inhibit the occurrence and development of colon cancer, possibly by inhibiting Survivin expression and promoting Caspase-3 expression, thereby enhancing the pro-apoptotic function.

Growth inhibition of subcutaneous tumor with glioma cells in nude mice by silencing TLR4

Zhansen An — 2024-06-05

This study investigated the regulatory impact of Toll-like receptor 4 (TLR4) gene on glioma cell proliferation and apoptosis, elucidating the molecular mechanisms underlying TLR4-induced growth inhibition in vivo. U-87MG-Sh and U-87MG-NC cells, with silenced TLR4 and negative control plasmid respectively, were established. Eighteen nude mice, divided into transfection, negative control, and blank control groups, were inoculated with corresponding cells. Over four weeks, the transfection group exhibited significantly reduced tumor growth rates, smaller mass and volume, and lower growth activity compared to controls. Histological analysis revealed sparse tumor cells, increased fibrous connective tissue, and slower angiogenesis in the transfection group. Flow cytometry demonstrated a lower proliferation index and increased G0/1 cell count in the transfection group. mRNA levels of TLR4, NF-κB, and CyclinD1 were significantly lower in the transfection group. TLR4 silencing correlated with U-87MG cell proliferation regulation, growth inhibition, NF-κB and CyclinD1 modulation, and induction of cell cycle arrest and apoptosis. These findings suggest TLR4 as a potential gene therapy target for glioma.

Effect of bone-marrow-derived mesenchymal stem cells on the rate of orthodontic tooth movements in rabbits

Rawand Jasim Othman — 2024-06-05

Mesenchymal stem cells from bone marrow, such as bone marrow aspirate concentrate (BMAC) and cultured and isolated bone marrow mesenchymal stem cells (BM-MSCs), have been used as therapeutic alternatives to enhance remodeling in the bone. Objective: This study aimed to evaluate the effects of BMAC and BM-MSCs on orthodontic tooth movements in rabbits. Methods: A100- gram nickel–titanium closed-coil springs were used to initiate orthodontic tooth movement of the lower first premolars in 35 male New Zealand rabbits for 21 days. Using a split-mouth design, autologous BMAC or BM-MSCs were submucosally injected into the right sides of the lower jaw, while the left sides served as the control. On days 7, 14, and 21, a three-dimensional digital model scan was used to measure the amount of tooth movement. The microfocus computed tomography (Micro-CT) and histological findings were examined on day 0 as the baseline measurement and on days 7, 14, and 21. Results: Compared to the control group, the quadrant receiving BMAC and BM-MSCs had a considerably greater amount of tooth movement. Histomorphometric analysis revealed that both BMAC and BM-MSCs had significantly higher numbers of osteoclasts and active bone-resorptive lacunae. The resorptive changes were greater in the BMAC and BM-MSCs groups than in the control group. Conclusion: The submucosal injection of BMAC and BM-MSCs accelerates orthodontic tooth movement (OTM) by decreasing bone density and supplying more osteoclast progenitor cells.

Determination of the signaling proteins responsible for the antioxidant potential of the Yishenhuoxue formula for treating asthenospermia in rats

Zhuojun Yuan — 2024-06-05

Asthenospermia is a predominant cause of male infertility, and antioxidant supplements can be effective in treating asthenospermia. We demonstrate the antioxidant potential of traditional Chinese medicine, the Yishenhuoxue (YSHX) formula, in treating polyglycosides of Tripterygium wilfordii (GTW)-induced asthenospermia in rats. Fifty male rats were randomly divided into the normal, model, and treatment groups. HE staining was used to evaluate the improvement of spermatogenic function of rats, and TBA reaction, qRT-PCR, Western Blot and other methods were used to determine the changes of oxidative stress indicators and to evaluate the improvement of antioxidant capacity of rats by YSHX. Comparison with the model group showed significant improvement in pathological damage caused by GTW to seminiferous tubules. MDA and NO content in rat testes decreased, especially in middle- and high-dosage groups. No significant changes were observed in SOD and CAT activity or mRNA expression. GSH-Px activity and GSH mRNA expression were significantly higher in the low-dosage group than in the model group. Compared to the model group, GR activity was significantly lower in the middle and high dosage groups, while the mRNA expression was higher. The PKC-beta level increased, while p-ERK1/2, NF-κB, and the ratio of p-ERK1/2*(ERK1/2)^-1 decreased significantly in the treatment groups. Therefore, YSHX can alleviate GTW-induced testicular damage, enhance GSH-Px activity, regulate GSH redox cycling, and mitigate oxidative stress injury. Furthermore, YSHX can promote PKC-beta expression and inhibit the phosphorylation of ERK1/2 and NF-κB. Using YSHX may be an effective way to increase sperm motility via the PKC-ERK1/2-NF-ĸB axis.

Nur77 induced by HIF-1α mediates vascular remodeling in hypoxic pulmonary hypertension

Congzheng Mao — 2024-06-05

Nur77 is a member of the NR4A subfamily of orphan nuclear receptors that is expressed and has a function within the immune system. This study aimed to investigate the role of Nur77 in hypoxic pulmonary hypertension. SPF male SD rats were exposed in hypobaric chamber simulating 5000 m high altitude for 0, 3, 7, 14, 21 or 28 days. Rat pulmonary artery smooth muscle cells (RPASMCs) were cultured under normoxic conditions (5% CO₂-95% ambient air) or hypoxic conditions (5% O₂ for 6 h, 12 h, 24 h, 48 h). Hypoxic rats developed pulmonary arterial remodeling and right ventricular hypertrophy with significantly increased pulmonary arterial pressure. The levels of Nur77, HIF-1α and PNCA were upregulated in pulmonary arterial smooth muscle from hypoxic rats. Silencing of either Nur77 or HIF-1α attenuated hypoxia-induced proliferation. Silencing of HIF-1α down-regulated Nur77 protein level, but Nur77 silence did not reduce HIF-1α. Nur77 was not con-immunoprecipitated with HIF-1α. This study demonstrated that Nur77 acted as a downstream regulator of HIF-1α under hypoxia, and plays a critical role in the hypoxia-induced pulmonary vascular remodeling, which is regulated by HIF-1α. Nur77 maybe a novel target of HPH therapy.

Effect of omega-3 fatty acid supplementation on markers of inflammation and endothelial function in patients with chronic heart disease: A systematic review and meta-analysis

Mohammed Ibrahim Mohialdeen Gubari — 2024-06-05

Chronic heart disease (CHD) is still a major global cause of morbidity and mortality, necessitating effective therapeutic interventions to mitigate its progression. Omega-3 fatty acids (FAs) have garnered attention for their potential anti-inflammatory and endothelial-protective properties in CHD management. The present study aims to assess the efficacy of Omega-3 FA supplementation on markers of inflammation and endothelial function in patients with CHD. To achieve this, we used the relevant keywords to search international databases (Web of Science, PubMed, Embase, and Scopus) and extract publications evaluating the effectiveness of omega-3 FA supplementation on inflammation markers and endothelial function in patients with CHD. STATA (version 15) and the random and fixed-effects models were used to evaluate the collected data. Thirteen clinical trial studies met inclusion criteria, with a total sample size of 853 individuals (406 cases and 447 controls). The cases had a mean age of 58 ± 10.3 years. The pooled results indicated that omega-3 Omega-3 FA supplementation significantly reduced the level of circulating IL-6 (SMD = -0.47, 95% CI -1.29 to 0.35, %, p < 0.001), hs-CRP (SMD = -0.21, 95% CI -0.70 to 0.28, p = 0.01), and TNF-α (SMD = -0.56, 95% CI -1.14 to 0.01, p < 0.001) in patients with CHD. Also, findings revealed that a daily supplement of omega-3 significantly increased FMD by 0.34% (95% CI: 0.14–0.54%, p < 0.001) as compared with placebo by a fixed-effect model in patients with CHD. These findings underscore the potential therapeutic utility of omega-3 fatty acid supplementation in modulating inflammation and endothelial dysfunction in patients with CHD.