Cellular and Molecular Biology

HIV-2 drug resistance genotyping and viral load among HIV-2 infected adults in Burkina Faso, West Africa

2024-11-27T07:58:02+01:00

HIV-2 infection although less virulent compared to HIV-1 is endemic in many parts of West Africa. In Burkina Faso, few data exist on HIV-2 genotypic resistance. The objective of this study was to assess HIV-2 genotypic resistance and viral load in adult patients infected with HIV-2 in Burkina Faso. This was a cross-sectional study that ran from February 2017 to March 2019. This study included 91 HIV-infected adult patients on ARV treatment. HIV and hepatitis B and C status were confirmed by serological tests. HIV-2 viral load and HIV-2 clusters were determined by in-house tests. The mean age was 58.99 ±8.66 years. Of the patients, 12.1% were HIV-1, 73.6% were HIV-2 and 14.3% were co-infected with HIV-1/HIV-2. Only 15% had a high viral load (more than 1000 copies/mL). Groups A and B were detected in this study with the majority being group A (23.75%). HIV-2 subtype CRF01_AB was found in 3.75% of HIV-2 patients. Of the 34 HIV-2 patients whose subtypes were determined, only 7 had reverse transcriptase and 3 had protease resistance mutations. The M184V mutation was the most detected. This study revealed recent data on the status of HIV-2 genotypic resistance in Burkina Faso. Although few HIV-2 infected patients on ARV treatment have developed resistance, it is important to establish a surveillance system for HIV-2 genotypic resistance.

Association of CASP8 rs3834129 and CTGF rs6918698 genotypes with susceptibility to colorectal cancer in a Mexican population

2024-11-27T07:58:20+01:00

Connective tissue growth factor (CTGF) and Caspase 8 (CASP8) have been implicated in cancer development and progression. Variants such as CASP8 rs3834129 (-652 6N I/D) and CTGF rs6918698 (-945 C>G) have been associated with several cancers, although their association is still debated between populations. This study investigates the possible association between the CASP8 rs3834129 and CTGF rs6918698 variants with colorectal cancer (CRC) in Mexican patients. Genomic DNA was extracted from 250 CRC patients and 250 control subjects. The identification of CASP8 and CTGF variants was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. The association was determined by the odds ratio (OR) analysis and P values were adjusted by the Bonferroni correction. Patients carrying the D/D genotype for the CASP8 rs3834129 variant exhibited an increased susceptibility to CRC (P = 0.012). The D/D genotype was associated with older 50-year-old patients (P = 0.006). In addition, this same D/D genotype was associated with TNM II stage (P = 0.013) and rectal localization (P = 0.023). Additionally, patients carrying the G/G genotype for the CTGF rs6918698 variant showed a decreased susceptibility to CRC (P = 0.009), and in the sex stratification, this gene has protective role in males (P = 0.008). This same genotype was associated with decreased susceptibility to early TNM stages (I+II) (P = 0.023) and right-sided colon tumor localization (P = 0.002). There was no association between response to treatment and the variants analyzed. Our findings suggest that the CASP8 rs3834129 and CTGF rs6918698 variants have a significant impact on the development of CRC.

Network-based meta-analysis and confirmation of genes ATP1A2, FXYD1, and ADCY3 associated with cAMP signaling in breast tumors compared to corresponding normal marginal tissues

2024-11-27T07:58:50+01:00

Breast cancer (BC) is a global health concern with a growing prevalence. Since BC is a heterogeneous cancer, transcriptome analyzes were carried out on breast tumor tissues relative to their corresponding normal tissues in order to identify gene expression signatures and perform meta-analysis. Five expression profiling by array data sets from breast tumor tissues and non-tumor neighboring tissues were retrieved following a search in the GEO database (GSE70947, GSE70905, GSE10780, GSE29044, and GSE42568). Meta-analysis of gene expression using the Network Analyst tool identified common differentially expressed genes and biological pathways in all data sets. Then, the DEGs were analyzed through PPI network construction, gene ontology, and pathway analysis. The detected hub genes underwent Kaplan–Meier (KM) plotter and UALCAN validation. Finally, Real-time PCR analysis was used on BC patients' samples to determine mRNA levels of cAMP signaling pathway members ATP1A2, FXYD1, and ADCY3. Breast tumor tissues showed 710 differentially expressed genes (DEGs), with 392 overexpressed and 318 underexpressed, compared to normal marginal tissues. On the EnrichR library, GO, and KEGG pathway analyses were performed on the DEGs list. Progesterone-mediated oocyte maturation and the NF-kappa B signaling system were upregulated DEGs' top deregulated signaling pathways. In contrast, pathways related to cancer and the cAMP signaling pathway were the most enriched terms for down-regulated genes. Next, Real-time PCR quantification of cAMP signaling cascade members ATP1A2, FXYD1, and ADCY3 was performed on 50 BC tumoral and non-tumoral tissues for validation. Results of meta-analyzed array data sets revealed DEGs representing BC gene signatures, and cAMP signaling pathway members as effective factors in BC. The results of our real-time PCR expression level determination for ATP1A2, FXYD1, and ADCY3 in breast tumor tissues relative to the normal margins contradicted our bioinformatics investigations, which found increased levels for these genes. Of these, only ATP1A2's expression levels were statistically significant. This study focused on identifying gene expression signatures that provide an invaluable source of evidence for BC-related underlying mechanisms to provide new therapeutic targets and biomarkers.

Inhibitory effect on acute herpes and prevention of postherpetic neuralgia in herpes simplex virus-1-infected mice using a plant extract Ricinus communis

2024-11-27T07:59:18+01:00

The present study aimed to examine the impact of Ricinus communis and valacyclovir (VACV) on the progression of skin lesions and pain responses in mice infected with herpes simplex virus type 1 (HSV-1). Mice were infected with HSV-1 and treated with R. communis (8, 16, or 48 mg/kg) or VACV (8, 25, or 90 mg/kg) twice daily on days 2–8 post-infection. Skin lesion development and pain-associated reactions were assessed 27 days after infection. HSV-1 infection results in zosteriform skin lesions and increased pain-related scores. Both R. communis and VACV demonstrated a dose-dependent reduction in skin lesions and pain-related ratings. The investigation also assessed the impact of the timing of R. communis and VACV administration on skin lesions and pain responses and found that lesion scores were significantly reduced when R. communis treatment was initiated on day 2 post-infection. Additionally, the inhibitory effects of R. communis and VACV on HSV-1 dissemination in the dorsal root ganglia (DRG) were studied. They showed a significant reduction in HSV-1 DNA replication number after the administration of both drugs. This study aimed to investigate the impact of R. communis and VACV on the expressed mRNA levels of pain-associated factors in the spinal cord of HSV-1-infected mice. The findings of this study demonstrated that R. communis therapy exhibited an inhibitory effect on pain-related factors. Overall, these findings suggest R. communis may have the potential to serve as a therapeutic agent for managing skin damage and pain-related responses caused by HSV-1.

Evaluation of HOTAIR, HOXD8, HOXD9, HOXD11 gene expression levels in Turkish patients with acute and chronic myeloid leukemia: A single center experience

2024-11-27T07:59:40+01:00

Homeobox (HOX) transcript antisense RNA (HOTAIR) and HOX genes are reported to be more expressed in various cancers in humans in recent studies. The role of HOTAIR and HOXD genes in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) is not well known. In this study, expression levels of HOXD8, HOXD9 and HOXD11 from HOXD gene family and HOTAIR were determined from peripheral blood samples of 30 AML and 30 CML patients and 20 healthy volunteers by quantitative Real Time PCR. We determined that the expression levels of HOXD9 and HOXD11 in the AML patients were significantly lower than the control group (p<0.001 and p=0.002, respectively). There was no significant difference in the expression levels of HOTAIR and HOXD8 when compared to the control group. In the CML patients there was a significant increase in the expression level of HOTAIR when compared to the control group (p=0.002). The expression levels of HOXD9 and HOXD11 were found to be significantly lower than the control group (p<0.001). Our study showed that HOTAIR may not be a biomarker in the diagnosis and is not significantly correlated with the clinicopathological prognostic characteristics of AML. Additionally; it can be said that HOTAIR is oncogenic by suppressing the expression of HOXD9 and HOXD11 but not HOXD8 in CML patients. The expression profiles of HOTAIR may be a potential biomarker in the diagnosis of CML patients in predicting and monitoring drug resistance.

The relationship of serum vaspin level with clinical parameters in patients with fibromyalgia syndrome

2024-12-20T08:57:25+01:00

Vaspin plays a regulatory role in lipid and glucose metabolism and is a therapeutic adipokine against impaired glucose intolerance in obese individuals. We aimed to investigate serum vaspin levels in patients with FMS and whether there was any relationship between vaspin levels and metabolic and clinical parameters in fibromyalgia. A total of 64 female patients who applied to an outpatient clinic due to widespread pain lasting more than three months were included in the study. The patients were divided into two groups: 32 in the fibromyalgia group and 32 in the healthy controls. The socio-demographic characteristics of the patients were evaluated with the standard evaluation form. Age, weight, height, blood pressure, body mass index (BMI), waist circumference, presence of menopause were recorded. Pain intensity was evaluated with visual analogue scale (VAS). The Fibromyalgia Impact Scale (FIS) was utilized to measure quality of life and functional status. Metabolic syndrome components were significantly different in the fibromyalgia group compared to the control group (p <0.05). While 22 patients (68.8%) in the fibromyalgia group met the diagnostic criteria for metabolic syndrome, three patients (9.4%) in the control group met these criteria. In the fibromyalgia intra-group correlation, vaspin was significantly positively correlated with BMI and waist circumference (p<0.05). In the control group, vaspin indicated a statistically significant positive correlation with BMI. This study elaborated that waist circumference, insulin, and insulin resistance were significantly higher in the fibromyalgia patients compared to the healthy control group. This was confirmed by the finding that significantly more patients met the diagnostic criteria for metabolic syndrome. Additionally, vaspin was considerably higher in fibromyalgia patients and thus it was positively correlated with BMI and waist circumference.

Prebiotics and iron fortification among women of reproductive age group - Is there an association with liver and renal function tests?

2024-11-27T08:00:27+01:00

Iron fortification compounds are of special interest to treat iron deficiency anemia, however, the dose-response effects of these fortificants on liver and renal functions have not been extensively reported in human subjects. The present study determines the effects of prebiotics and iron fortificants on liver function tests (LFTs) and renal function tests (RFTs) among women of reproductive age (WRA). A double-blind randomized controlled trial was performed for the duration of 90 days. A total of 75 iron-deficient women were selected and randomly divided into 5 groups (4 treatment groups and 1 control group). For this purpose, four different types of fortified wheat flour were prepared using two iron fortificants (NaFeEDTA and FeSO₄) and two prebiotics (Inulin and Galacto oligosaccharides) were given to four treatment groups, while control groups were only given iron-fortified flour without the addition of prebiotics. Blood samples were collected every month to evaluate Liver Function Tests, including Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP), total bilirubin and Renal Function Tests, including serum urea and creatinine. Our results found that prebiotic and iron-fortified diets increased ALT, AST and total bilirubin levels among WRA. For AST, ALP and total bilirubin, our results found the highest increase in the treatment groups treated with prebiotics and iron fortificants at 963 mg/kg GOS + 15 ppm FeSO₄. Moreover, the highest values of ALT and serum creatine were seen in groups treated with 963 mg/kg Inulin + 20 ppm NaFeEDTA, while maximum value for serum urea could be seen in the group given 963 mg/kg GOS + 30 ppm FeSO₄. The study concluded that prebiotic and iron-fortified diets increased ALT, AST and total bilirubin levels among WRA.

Disease complex associated with begomoviruses infecting squash and cucumber in Saudi Arabia

2024-11-27T08:00:50+01:00

During the field visits in growing season of 2022 in Dammam Region of Saudi Arabia, begomovirus-like symptoms including leaf curling, leaf cupping, leaf distortion, vein thickening and reduced leaf size were observed in squash and cucumber fields. Twenty-five samples were collected from each crop and PCR amplification was done using general diagnostic begomovirus primers (AC-1048/AV-494 and Begomo I/Begomo II). The obtained results showed desired sized amplified DNA fragments (550 bp and 1.1 kb) according to the primer sites. Sequencing results were analyzed using BLAST and revealed the presence of three different bipartite begomoviruses which include Squash leaf curl virus (SqLCV) isolated from squash and cucmber, Watermelon chlorotic stunt virus (WmCSV) and Tomato leaf curl Palampur virus (ToLCPalV) isolated from squash. The highest nucleotide identity found was 99.4% with Egyptian SqLCV isolated from squash and the lowest similarity was 93.3% found with a USA isolate isolated from wheel cactus. Sequencing results of two isolates of WmCSV showed 100% sequence identity with each other, eight isolates from Palestine isolated from watermelon, two isolates from Mexico isolated from prickly pear cactus and Watermelon, one isolate from each Lebanon and Jordan isolated from melon and wild mustard respectively. The lowest identity (87%) was found with a Saudi Arabian isolate isolated from papaya. For ToLCPalV isolate showed the highest identity (100 %) with an already reported isolate of same virus from melon in Saudi Arabia and two isolates isolated from cucumber and cantaloupe in Iran. However, the lowest identity (95.3%) was found with an Indian isolate isolated from eggplant. This is the first investigation of complex viral disease caused by SqLCV, WmCSV and ToLCPalV on the basis of molecular characterization from squash and a SqLCV isolate from Cucumber in Saudi Arabia.

Short-term effects of retinoic acid on the proliferation of SH-SY5Y cells via mitophagy and apoptosis

2024-11-27T08:01:13+01:00

Neuroblastoma shows the highest lethality in childhood and has poor prognosis at high grade. Our objectives included determining how retinoic acid affected the growth of neuroblastoma cells and the relationship between chemicals unique to neurons and cell death processes like apoptosis and mitophagy. The 50% inhibitory concentration of retinoic acid on SH-SY5Y neuroblastoma cells was determined at the 24^th, 48^th and 72^nd hours. At the optimal concentration of retinoic acid on SH-SY5Y cells, Ki-67, cytochrome C, HIF-1α, Parkin, α-synuclein, DJ-1 and tyrosine β- hydroxylase gene expressions were determined by using RT-PCR. Tyrosine β-hydroxylase protein expression was assessed by ELISA. The optimal time and concentration for retinoic acid in SH-SY5Y cells was 10 μM at the 24^th hour. The decreased gene expressions of Ki-67, α-synuclein, DJ-1 and tyrosine β-hydroxylase were observed while Cyt C, HIF-1α and Parkin gene expressions were upregulated (p<0.001). Tyrosine β-hydroxylase protein expression increased at the 24^th and 72^nd hours although it decreased at the 48^th hour (p<0.001). Retinoic acid has short-term effect on the proliferation of SH-SY5Y neuroblastoma cells. It was observed that short-term retinoic acid treatment improved neurodegeneration parameters, but it decreased the proliferation by inducing mitophagy and apoptosis of SH-SY5Y neuroblastoma cells.

Anti-wrinkle activity of the ethanol extract of Aronia melanocarpa for development of the cosmeceutical ingredients

2024-11-27T08:01:35+01:00

Despite the abundance of natural biological resources in Aronia melanocarpa, there is still insufficient research specifically exploring the potential for developing cosmeceutical compositions utilizing this plant. To develop the ingredient with the cosmeceutical function, the anti-wrinkle effect of the ethanol extract of A. melanocarpa was investigated. The ethanol extract was prepared from the dried A. melanocarpa. DPPH radical scavenging activity was significantly increased by the ethanol extract of A. melanocarpa. Cell viability on CCD986Sk human fibroblast was not affected by the ethanol extract of A. melanocarpa. Moreover, the ethanol extract of A. melanocarpa demonstrated inhibition of both collagenase and elastase enzymes. Analysis through ELISA and western blotting revealed an elevation in collagen expression levels in CCD986Sk human fibroblasts treated with ethanol extract. Additionally, the extract induced migration and invasion in HaCaT human keratinocytes, potentially associated with the activation of tight junctions. These results offer insights for the development of innovative cosmeceutical formulations utilizing A. melanocarpa extract.

Impact of COVID-19 infection on cyclooxygenase-2 gene expression and mast cell count in testicular tissue of azoospermic men

2024-12-04T16:38:46+01:00

The COVID-19 pandemic has posed significant threats to human life and health. Numerous studies have shown that men are more vulnerable to this infection, and recent evidence suggests that the presence of angiotensin-converting enzyme 2 (ACE2) receptors in male reproductive tissues may particularly predispose them to viral infection. Therefore, it is crucial to assess the potential impact of COVID-19 infection on male fertility. This study investigates the relationship between COVID-19 and the expression of inflammatory proteins, particularly mast cells and cyclooxygenase-2 (COX-2), in the testicular tissue of azoospermic men undergoing testicular sperm extraction (TESE). The study included 41 TESE candidates who were referred to the Besat Infertility Treatment Center in Kurdistan, Iran. Demographic information, such as age, was recorded for each participant. The subjects were divided into two groups: 20 non-infected and 21 infected with COVID-19. Testicular tissue samples were fixed in formalin and prepared for microscopic examination using toluidine blue staining and immunohistochemistry to assess the distribution and number of mast cells and COX-2 positive cells. Data analysis was performed using SPSS software version 27. The results showed that COX-2 gene expression and the number of mast cells were significantly higher in individuals infected with COVID-19 compared to the non-infected group. This increase in gene expression and mast cell count indicates elevated inflammation in the testicular tissue of COVID-19-infected individuals, which could lead to reduced fertility. This study aligns with previous research highlighting the role of inflammation in testicular tissue damage and decreased fertility.

EGCG inhibits the oxidative damage induced by TiO2-NPs in human colon cell lines

2024-11-27T08:10:48+01:00

To assess the protective effects of (-)-Epigallocatechin-3-gallate (EGCG), a natural antioxidant, against cellular oxidative damage induced by titanium dioxide nanoparticles (TiO₂-NPs), Human Colon cells NCM460 and Colon Cancer cells SW620 were selected for this study. The cells were divided into three groups: control group, TiO₂-NPs (80 μg/mL) exposure group, and EGCG (20 μmol/L)+TiO₂-NPs (80 μg/mL) co-exposure group. The study evaluated the precipitation rate of TiO₂-NPs influenced by EGCG in a cell-free system. It also measured the levels of ROS, MDA, and total antioxidant capacity in the cells of each group. The uptake of TiO₂-NPs by the cells was assessed using the SSC_e/SSC₀ ratio, and genome instability was evaluated. The results demonstrated that the addition of 20 μmol/L EGCG to the system resulted in greater sedimentation of TiO₂-NPs compared to TiO₂-NPs alone (P<0.05). The SSC_e/SSC₀ values in the co-exposure group were significantly lower than those in the TiO₂-NPs alone group (P<0.001). TiO₂-NPs induced a higher oxidative stress index in the cells (P<0.001), while the co-exposure group exhibited a lower REDOX index (P<0.001). The combination of EGCG and TiO₂-NPs did not significantly affect genome instability in either cell line. Importantly, EGCG showed a certain inhibitory effect on oxidative damage to colon cells induced by TiO₂-NPs, with no significant difference observed between normal and cancer cells in terms of this protective effect. Conducting a comprehensive investigation into the interaction mechanism between EGCG and TiO₂-NPs is crucial for establishing a scientific foundation that can guide the optimal utilization of the antioxidant properties of EGCG to mitigate the toxicity associated with TiO₂-NPs.

Antiproliferative effects of hazelnut cell culture extract on the different cancer cell lines

2024-11-27T08:11:09+01:00

The increasing incidence of cancer has necessitated the discovery of novel anticancer compound sources. The presence of taxanes in hazelnut cell cultures has promoted new promising pharmacotherapeutic applications. The antiproliferative properties of hazelnut (Corylus avellana cv. ‘Kalınkara’) cell culture extracts against different human cancer cell lines (HeLa, MCF-7, MDA-MB-231, A549) with Beas-2B as control were evaluated. The cytotoxicity of C. avellana culture extract (5 µM, 10 µM, and 20 µM) on all cell lines was evaluated with xCELLigence Real Time Cell Analysis System. Mitotic activity (450-655 nm), BrdU activity (450-550 nm) and caspase 3,7 activity (490-520 nm) were analyzed with a spectrophotometer through 24, 48, and 72 hours. Based on the values obtained from the xCELLigence Cell Analysis System, a 10 µM concentration of the culture extract was assigned as the IC₅₀ dose. Culture extracts at 10 µM enhanced the reduction in the proliferation of all cancer cells assayed. The highest decrease in mitotic (59.32%) and BrdU (53.77%) activity was observed in A549 lung cancer cells. However, caspase 3,7 activity (35.08%) was the highest in aggressive MDA-MB-231 breast cancer cells. The culture extracts decreased the viability of A549 cells to a greater extent than that of MCF-7 and MDA-MB-231 breast, and HeLa cervical cancer cells. C. avellana cv. ‘Kalınkara’ cell culture extracts have potential use in the treatment of lung and, to a lesser extent, breast and cervical cancers.

Influence of Azadirachta indica leaf extracts on tumor necrosis factor-α and interleukin-6 in albino rats and its computational analysis

2024-11-27T08:11:44+01:00

The current study was designed to investigate the effect of A. indica (Neem) leaf extracts (ethanolic and aqueous) in yeast-induced pyrexia and acetic acid-induced writhing in rat models to evaluate the antipyretic and analgesic biomarkers and its phytochemical screening with computational analysis. For the antipyretic activity model 60 albino rats (160-200g) of either sex were divided into 4 groups and all groups were injected with yeast to induce pyrexia. Out of 4 groups, first group (control) consisted of 6 rats, treated with normal saline, the second group (standard) comprised 6 rats, treated with paracetamol. Third and fourth experimental groups consisted of 48 rats, treated with A. indica leaf ethanolic and aqueous extracts at doses of (50, 100, 200 and 400mg/kg b.w). For analgesic activity group division was the same and all groups were injected with acetic acid to induce pain TNF-α and IL-6 levels were measured using ELISA kits after blood samples were taken and serums were separated. An acute toxicity study was performed. In molecular docking, nimbandiol and nimbolide were used as ligand molecules to target protein Tnf-α and IL-6. In both activities at the dose of 400mg/kg, group III showed significant inhibition (p<0.05). Biomarkers showed significant results at the dose of 400mg/kg. Phytochemical screening was performed to reveal the existence of various active constituents. In molecular docking, nimbandiol and nimbolide showed -5 and -5.3 binding energies respectively, as compared to the standard drug paracetamol with -4.2 binding energy to TNF-Alpha protein. Therefore, A. indica extracts can be used as a valuable drug for the treatment of pain and fever.

Genetic diversity and infectivity analysis of tomato yellow leaf curl virus Oman and its associated betasatellite

2024-11-27T08:12:05+01:00

Tomato yellow leaf curl virus-Oman (TYLCV-OM), a variant of the Tomato yellow leaf curl virus-Iran (TYLCV-IR) strain, was identified in 2005 as the cause of tomato yellow leaf curl disease (TYLCD) in Oman and is associated with a betasatellite namely as Tomato leaf curl betasatellite (ToLCB). Surveys were carried out from three diverse Governorates of Oman to investigate the correlation between the betasatellite and the virus. The visual assessment and scoring of infected tomato plants in the field revealed that the association of betasatellite with the disease was highest in Sharqia at 77%, followed by Dakhlia at41% and lowest in Batinah at30% . Ten isolates from three distinct regions of Oman were analyzed: two from Al Batinah, two from A'Dakhliah, and six from A'Sharquiah. All TYLCV-OM isolates were identified as variants of the 2005 isolates Al Batinah. However, a new recombinant form of TYLCV-OM, which could impact its virulence or spread, was identified in the Al Batinah region. Mutations observed in the Al Batinah isolates of TYLCV-OM coincided with recombination events involving ToLCOMV. Examination of the intergenic regions (IRs) of TYLCV-OM and ToLCOMV indicated that recombination occurred within the IR. Specifically, TYLCV-OM acquired a segment spanning coordinates 1 to 132 nt from ToLCOMV, which may influence its genetic diversity. The implications of these findings for the evolutionary dynamics of the begomovirus complex associated with yellow leaf curl disease are discussed. Inoculation of infectious construct of TYLCV-OM alone or with ToLCB resulted in severe leaf curl symptoms but leaf yellowing was more pronounced in the presence of ToLCB. Real-time quantitative data showed that TYLCV-OM was accumulated to higher level in the presence of betasatellite.

Comparison of pregnancy outcomes in amniocentesis recipients with normal and abnormal maternal serum analytes

2024-11-27T08:12:30+01:00

Considering the relatively high frequency of genetic disorders associated with negative pregnancy outcomes, in this research, adverse pregnancy outcomes in amniocentesis patients were compared between two groups with normal and abnormal maternal serum analytes. This retrospective cohort study was conducted on singleton pregnant women who underwent amniocentesis and had fetuses with normal chromosomes at the perinatology clinic in Rasht. Eligible patients were divided into two groups of 307 people with normal and abnormal maternal serum analytes based on laboratory screening results. Adverse pregnancy outcomes were compared between the two groups. In a total of 614 pregnant women, adverse pregnancy outcomes were observed in 24% of the abnormal analyte group and 15% of cases in the normal analyte group. The association between adverse pregnancy outcomes and both normal and abnormal analytes was found to be statistically significant (p<0.05). the most common adverse pregnancy outcome was hypertensive disorders, which was more prevalent in the abnormal analyte group (10.7%). The presence of abnormal levels of free beta-human chorionic gonadotropin (free β-hCG) and inhibin-A factors were found to be associated with adverse pregnancy outcomes. Specifically, for each unit increase in inhibin-A level, the likelihood of experiencing an adverse pregnancy outcome was reported to be 1.83 times higher (OR=1.83, P=0.028). Similarly, the presence of abnormal free β-hCG values was associated with a 3.12 times higher chance of adverse pregnancy outcomes (OR=3.115, P=0.03). The utilization of serum analytes for first and second-trimester screening can be beneficial in the prediction of adverse pregnancy outcomes, particularly hypertensive disorders during pregnancy.

Reduction in integrin a3b1 modulates lung cancer motility and invasion through p70S6K-dependent E-cadherin localization

2024-11-27T08:12:53+01:00

In the current study, we investigated the effects and action mechanism of integrin a3b1 in modulating non-small cell lung cancer (NSCLC) growth and progression. Reduced expression of integrin a3 by RNA silencing in p53 wild-type A549 NSCLC cells inhibits cell migration and invasion, compared with those in control cells. These anti-migratory and anti-invasive properties in integrin a3-silenced cells were associated with epithelial cadherin (E-cadherin) distribution at cell-cell contacts, and these effects require the activation of p70 S6 kinase (p70^S6K) as evidenced by treatment with rapamycin. Disruption of E-cadherin or blockade of p70^S6K activation abrogated the ability of integrin a3-silencing to inhibit cell migration and invasion. In contrast, enhanced proliferation in integrin a3-silenced cells was not affected by the changes in E-cadherin expression. These findings demonstrate the ability of integrin a3b1 to differentially regulate NSCLC cell growth and progression depending on the p53 status, and suggest that integrin a3b1-p70^S6K-p53 network may be a promising target for the treatment of NSCLC.

The impact of different occlusal guard materials on Candida albicans proliferation in the oral cavity

2024-11-27T08:13:25+01:00

Candida albicans is an opportunistic fungal pathogen. It's a dimorphic fungus with hyphal form that can penetrate and proliferate the oral mucosa. Occlusal guard materials come into direct contact with the oral mucosa and saliva when worn for extended periods, the occlusal guard acts as a reservoir for C. albicans that imposes adverse oral or systemic effects, particularly in medically compromised patients. A randomized controlled trial was conducted among forty volunteers with a history of bruxism. The volunteers were divided into four groups, with each group assigned to wear occlusal guards made of one of the following materials: (Polyethylene Terephthalate-Glycol, Polymethyl methacrylate resin, Ethyl phenylphosphinate 3D printing resin and Chrome-Cobalt Alloy). The study samples were collected after one month, with an additional three months spent assessing C. albicans. A descriptive statistical analysis was performed and compared between groups with different time intervals. The statistical analysis revealed that C. albicans proliferation increased after three months of wearing the occlusal guards, however, the results showed non-significant differences (P = 0.914). Furthermore, the comparative analysis demonstrated that the highest proliferation of C. albicans was found with Polymethyl methacrylate and the least with Chrome-Cobalt Alloy. Within the limitations of this study, it was concluded that reducing wearing time will reduce pathogenic infection by C. albicans, and the occlusal guard with the chrome-cobalt alloy material was better than the other materials in this aspect.

The utility of modified RENAL nephrometry score in predicting the perioperative outcomes following open partial nephrectomy

2024-11-27T08:13:51+01:00

The RENAL nephrometry score (RNS) is a standardized approach for grading the complexity of renal masses, although it does not have a strong correlation with the perioperative outcomes of open partial nephrectomy. To address these issues, a modified RENAL has been proposed. The study's goal is to determine the usefulness of a modified RENAL nephrometry score in predicting perioperative outcomes after open partial nephrectomy. This interventional multicentric trial included 47 adult patients with T1N0M0 renal masses of 7 cm or less, which were appropriate for open partial nephrectomy. Salah et al. presented a modified R.E.N.A.L classification system, which was used to assess renal complexity. Demographics, anthropometrics, prior medical history, renal mass features, histological diagnosis, and perioperative data were all collected for examination. Logistic regression and receiver operator characteristic curve analysis were used to predict perioperative problems. The patients' average age was 52.0 ± 13.1 years, with a male-to-female ratio of 1.24:1. The modified R.E.N.A.L score averaged 9.6 ± 1.8. Perioperative problems occurred in 42.6% of cases. The moderate complexity group experienced a lengthier hospital stay (2.7 ± 0.6 days) than the mild complexity group (2.3 ± 0.5 days, p = 0.008). The R.E.N.A.L. score was identified as an independent predictor of perioperative complications (OR: 1.48; 95% CI: 1.03-2.26, p = 0.046), with an acceptable cut-off point of 8.7 (AUC = 0.68). The modified RENAL is an important tool for identifying renal malignancies based on their anatomic characteristics, which aids in the prediction of perioperative complication rates.

The emerging role of S100A4 and S100A14 proteins in colorectal cancer progression

2024-11-27T08:14:15+01:00

Colorectal cancer (CRC) is the third most frequent type of cancer and the second leading cause of cancer-related deaths globally. Despite a thorough understanding of its biology, etiology, and epidemiology, an estimated 1.8 million new cases are diagnosed each year, and 900000 people die as a result of malignancy. The current study aims to investigate the expression pattern of S100A4 and S100A14 proteins in CRC tissue specimens and a panel of cell lines. Furthermore, to explore the metastatic potential of the aforementioned proteins in relation to the epithelial-mesenchymal transition and their possible association with the clinical features of CRC. The present study involved 80 patients diagnosed with CRC. Upon identification of the sociodemographic and clinicopathological features of the participants, immunohistochemical studies were conducted to measure the expression pattern of the S100 proteins in CRC tissues. In addition to qPCR and western blot studies, a series of in vitro experiments were conducted in a panel of CRC cell lines to assess the effects of S100 protein expression in cell migration, invasion, and proliferation. The number of CRC patients with high S100A4 expression levels was considerably higher than those with low expression (p < 0.0001). S100A4 is positively correlated with TNM staging, nodal metastasis, distant metastasis, and perineural invasion and was statistically significant (p = 0.02, 0.01, 0.0001, and 0.02, respectively). In vitro studies demonstrated that S100A14 knockdown induced EMT and resulted in a substantial increase in cell proliferation, migration, and invasion in HT29 cells. Moreover, S100A4 knockdown substantially inhibited migration, invasion, and proliferation in LoVo cells. The findings collectively suggest that both S100A4 and S100A14 play a pivotal role in colorectal cancer progression. Overexpression of S100A4 consistently with S100A14 downregulation is associated with the activation of epithelial-mesenchymal transition, which in turn enhances cell proliferation, migration, and invasion.

Assessment of decreased ovarian reserve and systemic inflammatory markers

2024-11-27T08:14:46+01:00

Given the significance of investigating ovarian reserve in infertile women, the limitations of existing diagnostic tests, and the absence of similar studies in this area, the present study aimed to examine the relationship between systemic inflammatory markers in patients with diminished ovarian reserve referred to the fertility clinic of Alzahra Hospital in Rasht in the year 2023. This cross-sectional analytical study was conducted on 174 patients referred to the Alzahra Hospital fertility clinic in Rasht. Patients were divided into two categories based on their serum levels of anti-Müllerian hormone (AMH):AMH >1.1 (ng/ml) and AMH < 1.1(ng/ml). Demographic and laboratory variables, including age, BMI, parity, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), red cell distribution width-to-platelet ratio (RPR), and follicle-stimulating hormone (FSH), were compared between the two groups. Significant difference between the two study groups regarding age and BMI, with the mean age and BMI of patients in the group with normal ovarian reserve being lower than those in the group with poor ovarian reserve. There was a significant difference in FSH levels, the group with poor ovarian response had higher FSH levels. Age and FSH were identified as independent predictive variables associated with diminished ovarian reserve in patients. According to the present study, a significant association between diminished ovarian reserve and inflammatory markers (NLR, PLR, and RPR) was not observed. However, FSH levels were significantly higher in the Diminished Ovarian Reserve (DOR) group. Furthermore, a meaningful correlation was only found between diminished ovarian reserve and age.

Harnessing natural compounds for PIM-1 kinase inhibition: A synergistic approach using virtual screening, molecular dynamics simulations, and free energy calculations

2024-11-27T08:15:10+01:00

Cancer has substantial economic ramifications for healthcare systems. PIM kinases, specifically PIM-1, are commonly upregulated in different types of cancers, thereby promoting cancer development. PIM-1 inhibitors have garnered interest for their potential efficacy in cancer therapy. This study used computational methods to screen a library of 7,600 natural compounds targeting the PIM-1 active site. Five top candidates—ZINC00388658, ZINC00316459, ZINC00197401, ZINC00001673, and ZINC00316479—were selected for subsequent interaction studies, which involved molecular dynamics simulations (MDS) and free energy calculation using the MMPBSA method. These compounds interacted with key PIM-1 residues and had multiple common binding site interactions with the co-crystallized ligand 6YN, which was used as a control. Furthermore, the selected compounds exhibited favorable drug-like properties and stable docked complexes during a 200-ns molecular dynamics simulation, followed by MMPBSA analysis. Among the candidates, ZINC00388658 had the most favorable binding energy profile, indicating exceptional stability and intense interaction with PIM 1. This makes ZINC00388658 the most promising candidate for further development as a PIM-1 inhibitor. These findings suggest that ZINC00388658 and other promising compounds hold significant potential for developing new cancer therapies that target PIM-1.

Protective role of vitamin B6 on some histological changes in the liver and kidneys and measure some indicators of oxidation balance in male rats

2024-11-27T08:15:36+01:00

This study aimed to evaluate the therapeutic effects of B6 in rats experimentally intoxicated by benzopyrene. Twenty-eight Male Sprague Dawley (white Swiss) rats weighing 170-210 g and 3-4 months old were utilized in this examination. Rats were divided into 4 control groups (G1), B[a]P 2 pmol/μL (G2), B6 only once per 2 days for a full month at 1000 mcg (15 dose per month) (G3), B6 + B[a]P (G4). The results showed an increase in the level of MDA and a significant decrease in the level of GSH in the second group compared to the negative control group, while no significant differences appeared in the third group, while a significant decrease in the level of MDA and a significant increase in the level of GSH were observed in the fourth group when compared with The second group. Hepatic and renal tissues were taken for histopathological study. The results showed that liver and kidney of G1 and G3 exhibit normal architecture. Liver of G2 revealed blood congestion in certain sinusoids and atrophied hepatocytes, there was also hyperplasia of Kupffer cells in the pockets of blood sinusoids, while renal tissues showed inflammatory cell infiltration, mesangial cell hyperplasia, and blood vessel congestion and bleeding. In contrast liver and kidney tissues in G4 showed mild lesion after B6 treatment. In conclusion, Pyredoxin (B6) can alleviate the hepatic and renal tissues damaged caused by benzopyrene.

Molecular characterization of virulence genes and influence of Xanthium strumarium extract against two Enterobacter species isolated from some soil invertebrates

2024-11-27T08:16:02+01:00

The development of bacterial antibiotic resistance poses a danger to healthcare systems worldwide. To reduce the spread of disease, researchers are looking for novel measures to control bacterial infections to reduce the spread of disease. The antibacterial properties of Xanthium strumarium methanolic and ethanolic extracts were evaluated against Enterobacter cloacae and E. hormaeche isolated from some invertebrates (Porcellio laevis, Armadillidium sp. (isopods), and Archispirostreptus syriacus). All Enterobacter strains tested positive for the presence of the virulence genes csgA, csgD, AcrAB, fimH, and Hsp60. Extracts of X. strumarium had significant anti-biofilm activity against E. cloacae and E. hormaechei. The disruption of established biofilm growth by the plant samples proved to be effective against E. cloacae and E. hormaechei. Both E. cloacae and E. hormaechei showed inhibition of biofilm formation and promotion of biofilm eradication in response to X. strumarium extract. Phenolic compounds such as ferulic acid, chlorogenic acid, and trans-cinnamic acid, and flavonoids such as kaempferol were the most abundant components in the extract and might play crucial roles in the extract's antibacterial and antibiofilm action. Results suggest that ethanolic leaf extracts from X. strumarium show potential as a novel approach to prevent infections caused by E. cloacae and E. hormaechei.

Unraveling the impacts of progressive drought stress on the photosynthetic light reaction of tomato: assessed by chlorophyll-a fluorescence and gene expression analysis

2024-11-27T08:16:26+01:00

The present study aimed to investigate the impact of progressive drought stress (100%, 75%, 50%, and 25% of field capacity) on photosynthetic light reactions of tomato plants. The imposed drought caused a gradual reduction in leaf RWC leading to a decline in pigment concentration and growth indices. Significant alteration in the OJIP fluorescence transient curves and the formation of specific fluorescence bands (L, K, J, H, and G) gradually increased as drought severity increased. Phenomenological energy fluxes per excited cross-section (ABS/CS, TRo/CS, DIo/CS, ETo/CS and RC/CS) decreased with intensifying drought. As drought stress progressed, JIP-test parameters including The efficiencies of light reactions [φPo/(1- φPo )], the efficiencies of redox reactions [(ψo/(1-ψo)] and the efficiency of PSI to reduce the last electron acceptors [δRo/(1−δRo)] were significantly attenuated. The quantum yields for primary photochemistry (φPo), electron transfer from Q_A to Q_B (yO), electron transport (φEo), and reduction of end electron acceptors at the PSI acceptor side (φRo) were negatively affected by drought stress. These results indicate that drought progression leads to structural and functional damage in PSII, characterized by a decrease in active reaction centers, reduced energy absorption and trapping, diminished energetic connectivity within PSII, and inhibition of the oxygen-evolving complex. Additionally, reduced plastoquinone pool size, over-reduction of plastoquinone, and impaired redox state downstream of Q_B were observed at the donor side of PSII. The quantum yield and efficiency of PSI to reduce electron acceptors were reduced by drought progression. Our results showed that the transcript levels of PetE and PetF genes, encoding the key electron careers plastocyanin and ferredoxin, were significantly downregulated in response to an increase in drought severity, contributing to reduced PSI efficiency. The Transcript levels of PetE and PetF were reduced by 79% and 66% under 25% field capacity treatment, respectively. These results highlight critical points within the photosynthetic apparatus that are highly sensitive to drought, providing valuable insights into the mechanisms of drought-induced damage in tomato plants.