Apigenin protects from hepatorenal damage caused by lead acetate in rats.

Exposure to lead (Pb) is associated with serious health problems including hepatorenal toxicity. Apigenin is a natural-sourced flavonoid with promising antioxidant and anti-inflammatory effects. In this research, we investigated the potential protective role of apigenin against lead acetate (PbAc)-induced hepatorenal damage. Thus, this experiment studied the exposure of male Wistar Albino rats to apigenin and/or PbAc and their effects in comparison to the control rats. Apigenin administration decreased the levels of Pb and prevented the histopathological deformations in liver and kidney tissues following PbAc exposure. This was confirmed by the normalized levels of liver and kidney function markers. Additionally, apigenin inhibited significantly oxidative reactions through upregulating Nrf2 and HO-1, and activating their downstreamed antioxidants accompanied by a marked depletion of pro-oxidants. Moreover, apigenin decreased the elevated pro-inflammatory cytokines and inhibited cell loss in liver and kidney tissues in response to PbAc intoxication in both tissues. The obtained results demonstrated that apigenin could be used to attenuate the molecular, biochemical, and histological alterations associated with Pb exposure due to its potent antioxidant, anti-inflammatory, and antiapoptotic effects.

Toxicity, Safety, and Efficacy Studies on Mesenchymal Stem Cells Derived from Decidua basalis in Wistar Albino Rats by Intravenous and Subcutaneous Routes.

Ex vivo expanded decidua-basalis(DB)-derived mesenchymal stem cells (MSCs) obtained from single donors have demonstrated therapeutic benefits in in vitro and in vivo studies. In this report, the intravenous and subcutaneous administration of DB-MSCs obtained from five healthy donors was assessed considering clinical grade proliferation, accessibility, and toxic effects in Wistar albino rats. The ability of the obtained DB-MSCs for differentiating, as well as their expression of several cell surface markers and immunomodulatory activities, were all assessed. Clinical standard proliferated cells were administered to animals intravenously and subcutaneously in a series of preclinical models in order to assess their in vivo toxicity, general safety, and tumorigenic possibilities. We established that DB cells exhibit structural and functional traits with MSCs. At various doses supplied intravenously or subcutaneously, the research showed no fatality, abnormal response to therapy, or substantial pathological modifications in the rats. Furthermore, there was no indication of prenatal damage in the same animal species when the rats were repeatedly treated with DBMSCs. Thus, DBMSCs were demonstrated to be non-toxic, non-teratogenic, and non-tumorigenic. To determine whether they can be administrated to human patients without risk, more investigation is recommended.

Molecular Determination of Vascular Endothelial Growth Factor, miRNA-423 Gene Abnormalities by Utilizing ARMS-PCR and Their Association with Fetal Hemoglobin Expression in the Patients with Sickle Cell Disease.

Recent studies have indicated that microRNA and VEGF are considered to be genetic modifiers and are associated with elevated levels of fetal haemoglobin HbF, and thus they reduce the clinical impact of sickle haemoglobin (HbS) patients. This cross-sectional study was performed on clinical confirmed subjects of SCD cases. miR-423-rs6505162 C>T and VEGF-2578 C>A genotyping was conducted by ARMS-PCR in SCD and healthy controls. A strong clinical significance was reported while comparing the association of miR-423 C>T genotypes between SCD patients and controls (p = 0.031). The microRNA-423 AA genotype was associated with an increased severity of SCD in codominant model with odd ratio (OR = 2.36, 95% CI, (1.15-4.84), p = 0.018) and similarly a significant association was observed in recessive inheritance model for microRNA-423 AA vs (CC+CA) genotypes (OR = 2.19, 95% CI, (1.32-3.62), p < 0.002). The A allele was associated with SCD severity (OR = 1.57, 95% CI, (1.13-2.19), p < 0.007). The distribution of VEGF-2578 C>A genotypes between SCD patients and healthy controls was significant (p < 0.013). Our results indicated that in the codominant model, the VEGF-2578-CA genotype was strongly associated with increased SCD severity with OR = 2.56, 95% CI, (1.36-4.82), p < 0.003. The higher expression of HbA1 (65.9%), HbA2 (4.40%), was reported in SCD patients carrying miR-423-AA genotype than miR-423 CA genotype in SCD patients carrying miR-423 CA genotype HbA1 (59.98%), HbA2 (3.74%) whereas SCD patients carrying miR-423 CA genotype has higher expression of HbF (0.98%) and HbS (38.1%) than in the patients carrying AA genotype HbF (0.60%), HbS (36.1%). ARMS-PCR has been proven to be rapid, inexpensive and is highly applicable to gene mutation screening in laboratories and clinical practices. This research highlights the significance of elucidating genetic determinants that play roles in the amelioration of the HbF levels that is used as an indicator of severity of clinical complications of the monogenic disease. Further well-designed studies with larger sample sizes are necessary to confirm our findings.

Camels' biological fluids contained nanobodies: promising avenue in cancer therapy.

Cancer is a major health concern and accounts for one of the main causes of death worldwide. Innovative strategies are needed to aid in the diagnosis and treatment of different types of cancers. Recently, there has been an evolving interest in utilizing nanobodies of camel origin as therapeutic tools against cancer. Nanotechnology uses nanobodies an emerging attractive field that provides promises to researchers in advancing different scientific sectors including medicine and oncology. Nanobodies are characteristically small-sized biologics featured with the ability for deep tissue penetration and dissemination and harbour high stability at high pH and temperatures. The current review highlights the potential use of nanobodies that are naturally secreted in camels' biological fluids, both milk and urine, in the development of nanotechnology-based therapy for treating different typesQuery of cancers and other diseases. Moreover, the role of nano proteomics in the invention of novel therapeutic agents specifically used for cancer intervention is also illustrated.

Zingiberene exerts chemopreventive activity against 7,12-dimethylbenz(a)anthracene-induced breast cancer in Sprague-Dawley rats.

Breast cancer is the primary cause of cancer-related death in females, wherein increased mortality of breast cancer patients is recorded worldwide. Zingiberene is a monocyclic sesquiterpene from the ginger plant and has many pharmacological benefits. In this exploration, we assessed the anticancer actions of Zingiberene against the 7,12-dimethylbenz(a)anthracene (DMBA)-stimulated mammary carcinogenesis in rats and MDA-MB-231 cells. Breast cancer was induced in the Female Sprague-Dawley rats through the 25 mg/kg of DMBA in 0.5 ml of corn oil and then treated with 20 and 40 mg/kg of Zingiberene, respectively. The body weight of animals and tumor volume was measured. Hematological parameters, transaminases, lipid profile, lipid peroxidation, and antioxidants status were scrutinized using standard techniques. The estrogen receptor-α and inflammatory markers were inspected by using respective assay kits. Histological damage scores were determined. In vitro experiments were conducted to scrutinize Zingiberene's effect on cell viability and apoptotic cell death in MDA-MB-231 cells. Zingiberene substantially modulated the DMBA-stimulated physiological and hematological changes and decreased the transaminases, and lipid peroxidation in the DMBA-stimulated animals. Zingiberene also elevated the antioxidant level and suppressed the inflammatory markers. Histological study revealed the protective effects of Zingiberene. The viability of MDA-MB-231 cells was noticeably diminished by the Zingiberene, thus inducing apoptotic cell death. Overall, our findings reliably proved the anticancer potential of Zingiberene against the DMBA-stimulated mammary tumorigenesis, and it could be a promising chemotherapeutic agent.

Avocado Seeds-Mediated Alleviation of Cyclosporine A-Induced Hepatotoxicity Involves the Inhibition of Oxidative Stress and Proapoptotic Endoplasmic Reticulum Stress.

Previous studies reported disrupted hepatic function and structure following the administration of cyclosporine A (CsA) in humans and animals. Recently, we found that avocado seeds (AvS) ameliorated CsA-induced nephrotoxicity in rats. As a continuation, herein we checked whether AvS could also attenuate CsA-induced hepatotoxicity in rats. Subcutaneous injection of CsA (5 mg/kg) for 7 days triggered hepatotoxicity in rats, as indicated by liver dysfunction, redox imbalance, and histopathological changes. Oral administration of 5% AvS powder for 4 weeks ameliorated CsA-induced hepatotoxicity, as evidenced by (1) decreased levels of liver damage parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin), (2) resumed redox balance in the liver (reduced malondialdehyde (MDA) and increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), (3) downregulated hepatic expression of endoplasmic reticulum (ER) stress-related genes (X-box binding protein 1 (XBP1), binding immunoglobulin protein (BIP), C/EBP homologous protein (CHOP)), and apoptosis-related genes (Bax and Casp3), (4) upregulated expression of the anti-apoptotic gene Bcl2, (5) reduced DNA damage, and (6) improved liver histology. These results highlight the ability of AvS to ameliorate CsA-induced hepatotoxicity via the inhibition of oxidative stress and proapoptotic ER stress.

Identification and Characterization of Novel Mutations in Chronic Kidney Disease (CKD) and Autosomal Dominant Polycystic Kidney Disease (ADPKD) in Saudi Subjects by Whole-Exome Sequencing.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a condition usually caused by a single gene mutation and manifested by both renal and extrarenal features, eventually leading to end-stage renal disease (ESRD) by the median age of 60 years worldwide. Approximately 89% of ADPKD patients had either PKD1 or PKD2 gene mutations. The majority (85%) of the mutations are in the PKD1 gene, especially in the context of family history. Objectives: This study investigated the genetic basis and the undiscovered genes that are involved in ADPKD development among the Saudi population. Materials and Methods: In this study, 11 patients with chronic kidney disease were enrolled. The diagnosis of ADPKD was based on history and diagnostic images: CT images include enlargement of renal outlines, renal echogenicity, and presence of multiple renal cysts with dilated collecting ducts, loss of corticomedullary differentiation, and changes in GFR and serum creatinine levels. Next-generation whole-exome sequencing was conducted using the Ion Torrent PGM platform. Results: Of the 11 Saudi patients diagnosed with chronic kidney disease (CKD) and ADPKD, the most common heterozygote nonsynonymous variant in the PKD1 gene was exon15: (c.4264G > A). Two missense mutations were identified with a PKD1 (c.1758A > C and c.9774T > G), and one patient had a PKD2 mutation (c.1445T > G). Three detected variants were novel, identified at PKD1 (c.1758A > C), PKD2L2 (c.1364A > T), and TSC2 (deletion of a'a at the 3'UTR, R1680C) genes. Other variants in PKD1L1 (c.3813_381 4delinsTG) and PKD1L2 (c.404C > T) were also detected. The median age of end-stage renal disease for ADPK patients in Saudi Arabia was 30 years. Conclusion: This study reported a common variant in the PKD1 gene in Saudi patients with typical ADPKD. We also reported (to our knowledge) for the first time two novel missense variants in PKD1 and PKD2L2 genes and one indel mutation at the 3'UTR of the TSC2 gene. This study establishes that the reported mutations in the affected genes resulted in ADPKD development in the Saudi population by a median age of 30. Nevertheless, future protein−protein interaction studies to investigate the influence of these mutations on PKD1 and PKD2 functions are required. Furthermore, large-scale population-based studies to verify these findings are recommended.

Oriental Hornet (Vespa orientalis) Larval Extracts Induce Antiproliferative, Antioxidant, Anti-Inflammatory, and Anti-Migratory Effects on MCF7 Cells.

The use of insects as a feasible and useful natural product resource is a novel and promising option in alternative medicine. Several components from insects and their larvae have been found to inhibit molecular pathways in different stages of cancer. This study aimed to analyze the effect of aqueous and alcoholic extracts of Vespa orientalis larvae on breast cancer MCF7 cells and investigate the underlying mechanisms. Our results showed that individual treatment with 5% aqueous or alcoholic larval extract inhibited MCF7 proliferation but had no cytotoxic effect on normal Vero cells. The anticancer effect was mediated through (1) induction of apoptosis, as indicated by increased expression of apoptotic genes (Bax, caspase3, and p53) and decreased expression of the anti-apoptotic gene Bcl2; (2) suppression of intracellular reactive oxygen species; (3) elevation of antioxidant enzymes (CAT, SOD, and GPx) and upregulation of the antioxidant regulator Nrf2 and its downstream target HO-1; (4) inhibition of migration as revealed by in vitro wound healing assay and downregulation of the migration-related gene MMP9 and upregulation of the anti-migratory gene TIMP1; and (5) downregulation of inflammation-related genes (NFκB and IL8). The aqueous extract exhibited the best anticancer effect with higher antioxidant activities but lower anti-inflammatory properties than the alcoholic extract. HPLC analysis revealed the presence of several flavonoids and phenolic compounds with highest concentrations for resveratrol and naringenin in aqueous extract and rosmarinic acid in alcoholic extract. This is the first report to explain the intracellular pathway by which flavonoids and phenolic compounds-rich extracts of Vespa orientalis larvae could induce MCF7 cell viability loss through the initiation of apoptosis, activation of antioxidants, and inhibition of migration and inflammation. Therefore, these extracts could be used as adjuvants for anticancer drugs and as antioxidant and anti-inflammatory agents.

Oleuropein protects against lipopolysaccharide-induced sepsis and alleviates inflammatory responses in mice.

Sepsis results from a major systemic inflammatory response and can induce disorders in multiple organs. The present study evaluated the potential protective effects of oleuropein (OLE) against hyperinflammatory responses during lipopolysaccharide (LPS)-induced sepsis in mice. Sixty male Balb/c mice were randomly categorized into five groups of 12 animals each: control, intraperitoneally injected with OLE (50 mg/kg), injected with LPS (10 mg/kg, intraperitoneal), and two groups administered OLE (25 and 50 mg/kg) for 3 days prior to LPS injection. Twenty-four hours after lipopolysaccharide injection, the animals were sacrificed. Serum, liver, and kidney tissue samples were collected for biochemical analyses, histopathological examinations, and investigation of inflammation-related gene expression. OLE pretreatment significantly reduced liver damage parameters (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase) and kidney damage parameters (blood urea nitrogen, creatinine, and kidney injury molecule-1) in the septic mice. OLE pretreatment ameliorated LPS-induced liver and kidney histological changes. OLE significantly mitigated the increased levels of malondialdehyde in the liver and kidneys and reduced levels of reduced glutathione induced by LPS. LPS injection also resulted in increased expression of the proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and inflammation-related genes (Nos2, Hmgb1, Mpo, Cd46, Map2k4, and Map2k7) in the hepatic and renal tissues. OLE reduced these expressions to ameliorate the inflammatory response. Moreover, OLE pretreatment enhanced the survival rate of septic mice. In conclusion, OLE alleviated the inflammatory response to protect against LPS-induced sepsis in mice.

Cytogenetics and the Revolution of Optical Genome Mapping in the Diagnosis of Diseases.

The study of chromosomal shape, characteristics, and behavior in somatic cell division (mitosis) during growth and development and in germ cell division (meiosis) during reproduction is known as cytogenetics. Many techniques can be used for cytogenetics, including fluorescent in situ hybridization (FISH), spectral karyotyping (SKY), multicolor FISH (M-FISH), microarray, and optical genome mapping (OGM). OGM is a novel genome-wide method that can identify structural variants (SVs) and copy number variants (CNVs) with only one test. Genomic structural information that is difficult to obtain with DNA sequencing can be promptly obtained with OGM, in which large molecule lengths can be mapped at a reasonable cost. OGM is increasingly being used to investigate chromosome abnormalities in genetic disorders and human cancer, but it was first utilized in genome assembly and research. According to recent research, OGM is capable of identifying every clinically significant variation seen in trials using conventional care. OGM is being utilized to identify genomic abnormalities in patients with malignancies and constitutional illnesses. It is regarded as a revolution in the field of cytogenetics. Rather than sequencing DNA, OGM relies on DNA labeling. Currently, the OGM technique with the Saphyr system from Bionano Genomics is a widely utilized platform for cytogenetic analysis. In conclusion, OGM can now be considered a highly reliable method for the identification of chromosomal abnormalities in the diagnosis of tumors and hematological diseases.

Unveiling the potency of FDA-approved oxidopamine HBr for cervical cancer regulation and replication proteins.

Cervical Cancer remains a women's health concern worldwide and ranks among the most prevalent cancers, particularly in developing countries. Many women are diagnosed with cervical cancer, with a substantial number succumbing to the disease even after the availability of vaccines and drugs. The tumour microenvironment often exhibits immune evasion, including suppression of T-cell activity and altered cytokine, impacting the efficacy of therapeutic interventions and highlighting the need for treatments to modulate the immune response. Despite efforts to promote HPV vaccination and regular screenings, it causes many deaths, underscoring the urgent need for continued research, healthcare access, and rapid drug development or repurposing. In this study, we identified various proteins involved in cervical cancer cell cycle regulation and DNA replication proteins, performed the multitargeted docking with an FDA-approved library, and identified Oxidopamine HBr as a multitargeted drug. Studies extended with pharmacokinetics and compared with the standard values followed by DFT, which supported the compound as a multitargeted inhibitor. Further, the docked complexes were taken for the interaction fingerprints, and it was identified that there are many 9 polar, 5 hydrophobic, 2 aromatic, and 2 basic residues. We extended our studies for 100ns MD Simulation in water, and the computations explored the deviation and fluctuations under 2Å and many intermolecular interactions; the same trajectory files were used for the MM\GBSA studies. All the studies have supported the Oxidopamine HBr as a cervical cancer multitargeted inhibitor-however, experimental studies are needed before human use.

Correction: Association of SNPs within TMPRSS6 and BMP2 genes with iron deficiency status in Saudi Arabia.

[This corrects the article DOI: 10.1371/journal.pone.0257895.].

COVID-19: Establishing, implementing and assessment safety strategy, descriptive interventional study.

The increase in severe acute respiratory syndrome SARS-CoV-2 has invariably affected medical professionals in their training, academic and professional development. The present study was an interventional descriptive study aimed at reducing the risk of exposure to COVID-19 and enabling physical attendance to the practical session for applied medical students by establishing and implementing a safety strategy. The adopted safety strategy has eight conditions and 50 requirements. Compliance with the safety strategy along with the serological diagnosis of COVID-19 was used as a key performance indicator for assessing the efficiency of the safety strategy. A total of 197 students were enrolled at the beginning of the study. The overall results showed that 78.1% of the respondents strictly followed the protocol, 14.5% of the individuals partially responded to the protocol and 7.4% of the individuals did not respond to the protocol. Twenty-two (12.6%) out of the 175 participants who completed the study had positive COVID-19 during the study period, whereas the remaining 153 participants (87.4%) appeared to be healthy. The serological results showed that 68 (38.9%) and 66 (37.7%) individuals of the study population had positive IgM+IgA and IgG of COVID-19, respectively; the majority of the participants who developed antibodies did not show symptoms and appeared to be healthy during the study. The physical distancing condition was the only condition that displayed a significant relationship with seropositive IgM+IgA. The compiling of standardized protocols along with serological diagnoses can be an effective tool in measuring the effectiveness of safety protocol and reducing the risk of exposure to COVID-19.

Interleukin-10 as Covid-19 biomarker targeting KSK and its analogues: Integrated network pharmacology.

COVID-19 caused by the SARS-CoV-2 virus is widespread in all regions, and it disturbs host immune system functioning leading to extreme inflammatory reaction and hyperactivation of the immune response. Kabasura Kudineer (KSK) is preventive medicine against viral infections and a potent immune booster for inflammation-related diseases. We hypothesize that KSK and KSK similar plant compounds, might prevent or control the COVID-19 infection in the human body. 1,207 KSK and KSK similar compounds were listed and screened via the Swiss ADME tool and PAINS Remover; 303 compounds were filtered including active and similar drug compounds. The targets were retrieved from similar drugs of the active compounds of KSK. Finally, 573 genes were listed after several screening steps. Next, network analysis was performed to finalize the potential target gene: construction of protein-protein interaction of 573 genes using STRING, identifying top hub genes in Cytoscape plug-ins (MCODE and cytoHubba). These ten hub genes play a crucial role in the inflammatory response. Target-miRNA interaction was also constructed using the miRNet tool to interpret miRNAs of the target genes and their functions. Functional annotation was done via DAVID to gain a complete insight into the mechanism of the enriched pathways and other diseases related to the given target genes. In Molecular Docking analysis, IL10 attained top rank in Target-miRNA interaction and also the gene formed prominent exchanges with an excellent binding score (> = -8.0) against 19 compounds. Among them, Guggulsterone has an acute affinity score of -8.8 for IL10 and exhibits anti-inflammatory and immunomodulatory properties. Molecular Dynamics simulation study also performed for IL10 and the interacting ligand compounds using GROMACS. Finally, Guggulsterone will be recommended to enhance immunity against several inflammatory diseases, including COVID19.

Corrigendum: Melatonin ameliorates serobiochemical alterations and restores the cardio-nephro diabetic vascular and cellular alterations in streptozotocin-induced diabetic rats.

[This corrects the article DOI: 10.3389/fvets.2023.1089733.].

Melatonin downregulates the increased hepatic alpha-fetoprotein expression and restores pancreatic beta cells in a streptozotocin-induced diabetic rat model: a clinical, biochemical, immunohistochemical, and descriptive histopathological study.

Background: Diabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes. Objective: This study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how ß-cells of the pancreas in diabetic rats respond to MT administration. Materials and methods: Forty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively. Results: MT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the ß-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic ß-cells; its antioxidant effect also reduced hepatocyte injury. Conclusion: Collectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic ß-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes.

Thymoquinone counteracts oxidative and inflammatory machinery in carrageenan-induced murine paw edema model.

Thymoquinone (TQ) is an active constituent in Nigella sativa (black cumin) and is extensively reported for its distinguished antioxidant and anti-inflammatory bioactivities. Despite the local protective response of acute inflammation, it contributes to the development of various disease conditions such as cell death, organ damage, or carcinogenesis. Hence, in this study, the effects of orally administered TQ (50 mg/kg and 100 mg/kg) for 14 days against edema development, oxidative stress, and inflammation were investigated in paw edema induced by carrageenan in mice. Indomethacin (10 mg/kg) was used as a reference drug. The results revealed that TQ reduced the paw edema volume in a time-dependent manner, attenuated acetic acid-provoked writhing movements, and reduced xylene-triggered ear edema. Hematological findings revealed marked normalization of altered counts of WBCs, and platelets. Furthermore, paw tissue levels of malondialdehyde and nitric oxide showed marked decreases together with increases in nuclear factor erythroid 2-related factor 2, glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase after TQ administration. Additionally, TQ decreased pro-inflammatory mediators, such as interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein-1, C-reactive protein, myeloperoxidase, and nuclear factor kappa-B in the inflamed paw tissue. Moreover, appreciable decreases were recorded in cyclooxygenase-2 and its product prostaglandin E2 and the immune reaction of tumor necrosis factor-alpha in TQ-treated mice. Histopathological findings further validated the potential antiedematous, anti-inflammatory power of TQ in inflamed tissues. Conclusively, the results encourage the potent application of TQ to subside acute inflammatory events because of its striking antioxidant and anti-inflammatory properties in inflamed paw tissue.

Antiapoptotic Gene Genotype and Allele Variations and the Risk of Lymphoma.

BACKGROUND: The findings of earlier investigations of antiapoptotic gene genotypes and allele variants on lymphoma risk are ambiguous. This study aimed to examine the relationship between the mutation in the antiapoptotic genes and lymphoma risk among Saudi patients. METHODS: This case-control study included 205 patients, 100 of whom had lymphoma (cases) and 105 who were healthy volunteers (controls). We used tetra amplification refractory mutation polymerase chain reaction (PCR) to identify antiapoptotic genes such as B-cell lymphoma-2 (BCL2-938 C > A), MCL1-rs9803935 T > G, and survivin (BIRC5-rs17882312 G > C and BIRC5-rs9904341 G > C). Allelic-specific PCR was used to identify alleles such as BIRC5-C, MCL1-G, and BIRC5-G. RESULTS: The dominant inheritance model among cases showed that mutations in all four antiapoptotic genes were more likely to be associated with the risk of lymphoma by the odds of 2.0-, 1.98-, 3.90-, and 3.29-fold, respectively, compared to controls. Apart from the BCL-2-A allele, all three specified alleles were more likely to be associated with lymphoma by the odds of 2.04-, 1.65-, and 2.11-fold, respectively. CONCLUSION: Unlike healthy individuals, lymphoma patients are more likely to have antiapoptotic gene genotypes and allele variants, apart from BCL-2-A alterations. In the future, these findings could be used to classify and identify patients at risk of lymphoma.

Melatonin ameliorates serobiochemical alterations and restores the cardio-nephro diabetic vascular and cellular alterations in streptozotocin-induced diabetic rats.

Melatonin possesses a wide range of pharmacological activities, including antidiabetic properties. Diabetes mellitus (DM) induces several physiopathological changes in body organs, which could be observed lately after systemic failure. In the current study, we aimed to investigate the serobiochemical changes and the histopathological picture in the diabetic heart and the kidney early before chronic complications and highlight the association between hyperglycemia, glomerular alterations, and cardiovascular changes. In addition, the role of melatonin in the treatment of cardio-nephro diabetic vascular and cellular adverse changes in streptozotocin-induced diabetic rats was also studied. A total of 40 mature Wistar albino rats were distributed into five groups; (1) control untreated rats, (2) diabetic mellitus untreated (DM) rats, in which DM was induced by the injection of streptozotocin (STZ), (3) control melatonin-treated (MLT), (4) melatonin-treated diabetic (DM + MLT) rats, in which melatonin was injected (10 mg/kg/day, i.p.) for 4 weeks, and (5) insulin-treated diabetic (DM + INS) rats. The serum biochemical analysis of diabetic STZ rats showed a significant (P < 0.05) increase in the concentrations of blood glucose, total oxidative capacity (TOC), CK-MB, endothelin-1, myoglobin, H-FABP, ALT, AST, urea, and creatinine as compared to control rats. In contrast, there was a significant (P < 0.05) decrease in serum concentration of insulin, total antioxidative capacity (TAC), total nitric oxide (TNO), and total protein level in DM rats vs. the control rats. Significant improvement in the serobiochemical parameters was noticed in both (DM + MLT) and (DM + INS) groups as compared with (DM) rats. The histological examination of the DM group revealed a disorder of myofibers, cardiomyocyte nuclei, and an increase in connective tissue deposits in between cardiac tissues. Severe congestion and dilation of blood capillaries between cardiac muscle fibers were also observed. The nephropathic changes in DM rats revealed various deteriorations in glomeruli and renal tubular cells of the same group. In addition, vascular alterations in the arcuate artery at the corticomedullary junction and interstitial congestion take place. Melatonin administration repaired all these histopathological alterations to near-control levels. The study concluded that melatonin could be an effective therapeutic molecule for restoring serobiochemical and tissue histopathological alterations during diabetes mellitus.