Modulation of inflammatory, oxidative, and apoptotic stresses mediates the renoprotective effect of daidzein against glycerol-induced acute kidney injury in rats.

Acute kidney injury (AKI) is a life-threatening complication that accompanies rhabdomyolysis. Daidzein is a dietary isoflavone that has various biological activities. This study examined the therapeutic potential of daidzein and the underlying mechanisms against AKI induced by glycerol in male rats. Animals were injected once with glycerol (50%, 10 ml/kg, intramuscular) for induction of AKI and pre-treated orally with daidzein (25, 50, and 100 mg/kg) for 2 weeks. Biochemical, histopathological, immunohistopathological, and molecular parameters were assessed to evaluate the effect of daidzein. The results revealed that the model group displayed remarkable functional, molecular, and structural changes in the kidney. However, pre-administration of daidzein markedly decreased the kidney relative weight as well as the levels of urea, creatinine, K, P, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C. Further, daidzein lessened the rhabdomyolysis-related markers [lactate dehydrogenase (LDH) and creatine kinase (CK)]. Notably, the enhancement of the antioxidant biomarkers [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and reduced glutathione (GSH) is accompanied by a decrease in malondialdehyde (MDA) and nitric oxide (NO) levels. Moreover, upregulated gene expression levels of nuclear factor erythroid 2-related factor 2 (Nfe212) and hemeoxygenase-1 (Hmox1) were exerted by daidzein administration. Rats who received daidzein displayed markedly lower interleukin-1ß (IL-1ß), tumor nuclear factor-α (TNF-α), myleoperoxidase (MPO), and nuclear factor kappa B (NF-κB) levels together with higher interleukin-10 (IL-10) related to the model group. Remarkably, significant declines were noticed in the pro-apoptotic (Bax and caspase-3) and rises in antiapoptotic (Bcl-2) levels in the group that received daidzein. The renal histological screening validated the aforementioned biochemical and molecular alterations. Our findings support daidzein as a potential therapeutic approach against AKI-induced renal injury via suppression of muscle degradation, oxidative damage, cytokine release, and apoptosis.

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 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.

Human papillomavirus in cancer: Infection, disease transmission, and progress in vaccines.

Human papillomaviruses (HPVs) infect epithelial cells of human beings, and their replication cycle is associated with epithelial differentiation. More than 200 genotypes of HPVs were identified, and each of these HPVs shows distinct specificity for tissues and infection. HPV infection was involved in the development of lesions on the feet, genital warts and hands. The evidence of HPV infection revealed the role of HPVs in neck and head squamous cell carcinoma, esophageal cancer, cervical cancer, head and neck cancer, brain and lung tumours. The independent traditional risk factors, various clinical outcomes, and increased prevalence among certain populations and geographical regions have led increasing interest in HPV infection. The mode of HPVs transmission remains unclear. Moreover, in recent years, vertical transmission of HPVs was reported. This review concludes present knowledge about HPV infection, virulence strains, clinical significance of HPVs, and mode of transmission, and vaccination strategies.

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.

Asn215Ser, Ala143Thr, and Arg112Cys variants in α-galactosidase A protein confer stability loss in Fabry's disease.

Alpha galactosidase A (α-GalA) gene contains nine exons localized at the q-arm of the X chromosome. Generally, an α-GalA enzyme is involved in the removal of galactosyl moieties from the glycoproteins and glycolipids. Dysregulation results in the accumulation of glycoproteins as well as glycolipids in various organs leading to Fabry disease (FD). In this study, we examine the impact of Asn215Ser, Ala143Thr and Arg112Cys variants on the α-GalA protein structure contributing to functional dynamic changes in FD. The seven computational pathogenicity prediction methods were used to predict the effects of these variants on the α-GalA protein. The three-dimensional structure of α-GalA variants was modeled with the Swiss Model and Robetta server and validated using a variety of tools. Then, molecular dynamics (MD) simulation was performed to understand the stability and dynamic behavior of the wild-type and variants structures. Most of our analyzed pathogenicity prediction tools showed that Asn215Ser, Ala143Thr and Arg112Cys variants cause a deleterious effect on the α-GalA protein. Further, MD trajectory analysis showed the destabilizing effect of variants on α-GalA structure based on the root mean square deviation, root mean square fluctuation, solvent accessible surface area, the radius of gyration, hydrogen bond, cluster analysis and PCA analysis. This concludes that the presence of these variants could potentially affect the protein functional process of galactosyl moieties removal which might lead to Fabry disease.Communicated by Ramaswamy H. Sarma.

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.

Melatonin ameliorates the adrenal and pancreatic alterations in streptozotocin-induced diabetic rats: Clinical, biochemical, and descriptive histopathological studies.

Previous studies have demonstrated the beneficial effects of melatonin in diabetic rats. However, limited studies have been conducted on the potential effects of melatonin on the descriptive histopathological and morphometric findings in different compartments of the adrenal glands in diabetic animal models. In this study, using a streptozotocin (STZ)-induced diabetic rat model, we sought to examine histological alterations in the pancreas and adrenal glands and observe the effect of the administration of melatonin on the histopathology and morphology of the pancreas and the adrenal gland cortex and medulla that are altered by STZ-induced hyperglycemia. Rats were randomly assigned to four different groups: Group I, normal control; Group II, melatonin group (MT) (10 mg/kg/day); Group III, (diabetic STZ group), and Group IV, diabetic (STZ) + melatonin group (MT). Throughout the experiment, the animals' fasting blood sugar levels were measured. Blood was obtained to determine the animals' cumulative blood sugar levels after sacrification. For histological and morphometrical evaluations, the pancreatic and adrenal gland tissues were dissected and processed. Our results showed that diabetic rats receiving melatonin significantly (P < 0.05) improved their fasting blood sugar and cumulative blood sugar levels compared to the diabetic group not receiving melatonin. Furthermore, histopathological examinations of the pancreatic and adrenal tissues of the diabetic rats indicated the occurrence of severe histopathological and morphometric changes. Morphometric analysis of the adrenals indicated a significant increase (P < 0.05) in the thickness of the cortex zones [zona glomerulosa (ZG), zona fasciculata (ZF), and zona reticularis (ZR)] for the diabetic STZ group compared with other groups, and a significant decrease (P < 0.05) in the diameter of the in adrenal gland medullas in the diabetic STZ rats compared to the other groups. Furthermore, treatment with melatonin restored these changes in both the pancreatic and adrenal gland tissues and produced a significant (P < 0.05) improvement in the cortex and medulla thickness compared to the untreated diabetic rats. Overall, melatonin significantly reduced the hyperglycemic levels of glucose in diabetic rats and reversed the majority of histopathological alterations in the tissues of the pancreas and adrenals, demonstrating its anti-diabetic activity.

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.

Ameliorative Effects of Camel Milk and Its Exosomes on Diabetic Nephropathy in Rats.

Contradictory results were obtained regarding the effects of extracellular vesicles such as exosomes (EXOs) on diabetes and diabetic nephropathy (DN). Some studies showed that EXOs, including milk EXOs, were involved in the pathogenesis of DN, whereas other studies revealed ameliorative effects. Compared to other animals, camel milk had unique components that lower blood glucose levels. However, little is known regarding the effect of camel milk and its EXOs on DN. Thus, the present study was conducted to evaluate this effect on a rat model of DN induced by streptozotocin. Treatment with camel milk and/or its EXOs ameliorated DN as evidenced by (1) reduced levels of kidney function parameters (urea, creatinine, retinol-binding protein (RBP), and urinary proteins), (2) restored redox balance (decreased lipid peroxide malondialdehyde (MDA) and increased the activity of antioxidants enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)), (3) downregulated expression of DN-related genes (transforming growth factor-beta 1 (TGFß1), intercellular adhesion molecules 1 (ICAM1), and transformation specific 1 (ETS1), integrin subunit beta 2 (ITGß2), tissue inhibitors of matrix metalloproteinase 2 (TIMP2), and kidney injury molecule-1 (KIM1)), and (4) decreased renal damage histological score. These results concluded that the treatment with camel milk and/or its EXOs could ameliorate DN with a better effect for the combined therapy.

In silico investigations identified Butyl Xanalterate to competently target CK2α (CSNK2A1) for therapy of chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is an incurable malignancy of B-cells. In this study, bioinformatics analyses were conducted to identify possible pathogenic roles of CK2α, which is a protein encoded by CSNK2A1, in the progression and aggressiveness of CLL. Furthermore, various computational tools were used to search for a competent inhibitor of CK2α from fungal metabolites that could be proposed for CLL therapy. In CLL patients, high-expression of CSNK2A1 was associated with early need for therapy (n = 130, p < 0.0001) and short overall survival (OS; n = 107, p = 0.005). Consistently, bioinformatics analyses showed CSNK2A1 to associate with/play roles in CLL proliferation and survival-dependent pathways. Furthermore, PPI network analysis identified interaction partners of CK2α (PPI enrichment p value = 1 × 10-16) that associated with early need for therapy (n = 130, p < 0.003) and have been known to heavily impact on the progression of CLL. These findings constructed a rational for targeting CK2α for CLL therapy. Consequently, computational analyses reported 35 fungal metabolites out of 5820 (filtered from 19,967 metabolites) to have lower binding energy (ΔG: - 10.9 to - 11.7 kcal/mol) and better binding affinity (Kd: 9.77 × 107 M-1 to 3.77 × 108 M-1) compared with the native ligand (ΔG: - 10.8, Kd: 8.3 × 107 M--1). Furthermore, molecular dynamics simulation study established that Butyl Xanalterate-CK2α complex continuously remained stable throughout the simulation time (100 ns). Moreover, Butyl Xanalterate interacted with most of the catalytic residues, where complex was stabilized by more than 65% hydrogen bond interactions, and a significant hydrophobic interaction with residue Phe113. Here, high-expression of CSNK2A1 was implicated in the progression and poor prognosis of CLL, making it a potential therapeutic target in the disease. Butyl Xanalterate showed stable and strong interactions with CK2α, thus we propose it as a competitive inhibitor of CK2α for CLL therapy.

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.

BARD1 mystery: tumor suppressors are cancer susceptibility genes.

The full-length BRCA1-associated RING domain 1 (BARD1) gene encodes a 777-aa protein. BARD1 displays a dual role in cancer development and progression as it acts as a tumor suppressor and an oncogene. Structurally, BARD1 has homologous domains to BRCA1 that aid their heterodimer interaction to inhibit the progression of different cancers such as breast and ovarian cancers following the BRCA1-dependant pathway. In addition, BARD1 was shown to be involved in other pathways that are involved in tumor suppression (BRCA1-independent pathway) such as the TP53-dependent apoptotic signaling pathway. However, there are abundant BARD1 isoforms exist that are different from the full-length BARD1 due to nonsense and frameshift mutations, or deletions were found to be associated with susceptibility to various cancers including neuroblastoma, lung, breast, and cervical cancers. This article reviews the spectrum of BARD1 full-length genes and its different isoforms and their anticipated associated risk. Additionally, the study also highlights the role of BARD1 as an oncogene in breast cancer patients and its potential uses as a prognostic/diagnostic biomarker and as a therapeutic target for cancer susceptibility testing and treatment.

Developing a Multimodal Model for Detecting Higher-Grade Prostate Cancer Using Biomarkers and Risk Factors.

A technique to predict crucial clinical prostate cancer (PC) is desperately required to prevent diagnostic errors and overdiagnosis. To create a multimodal model that incorporates long-established messenger RNA (mRNA) indicators and conventional risk variables for identifying individuals with severe PC on prostatic biopsies. Urinary has gathered for mRNA analysis following a DRE and before a prostatic examination in two prospective multimodal investigations. A first group (n = 489) generated the multimodal risk score, which was then medically verified in a second group (n = 283). The reverse transcription qualitative polymerase chain reaction determined the mRNA phase. Logistic regression was applied to predict risk in patients and incorporate health risks. The area under the curve (AUC) was used to compare models, and clinical efficacy was assessed by using a DCA. The amounts of sixth homeobox clustering and first distal-less homeobox mRNA have been strongly predictive of high-grade PC detection. In the control subjects, the multimodal method achieved a total AUC of 0.90, with the most important aspects being the messenger riboneuclic acid features' PSA densities and previous cancer-negative tests as a nonsignificant design ability to contribute to PSA, aging, and background. An AUC of 0.86 was observed for one more model that added DRE as an extra risk component. Two methods were satisfactorily verified without any significant changes within the area under the curve in the validation group. DCA showed a massive net advantage and the highest decrease in inappropriate costs.

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.

In Silico Identification of Hub Genes as Observing Biomarkers for Gastric Cancer Metastasis.

Perception of hub genes engaged in metastatic gastric cancer (mGC) promotes novel ways to diagnose and treat the illness. The goal of this investigation is to recognize the hub genes and reveal its molecular mechanism. In order to explore the potential facts for gastric cancer, the expression profiles of two different datasets were used (GSE161533 and GSE54129). The genes were confirmed to be part of the PPI network for gastric cancer pathogenesis and prognosis. In Cytoscape, the CytoHubba module was used to discover the hub genes. Responsible hub genes were identified. Data from Kaplan-Meier plotter confirmed the predictive value of these distinct genes in various stages of gastric malignancy. Upregulated and downregulated genes were identified to utilize for further analysis. Positive regulation by a host of viral process, positive regulation of granulocyte differentiation, negative regulation of histone H3-K9 methylation were found in DEGs analysis. In addition, five KEGG pathways were identified as an essential enhancer that include nucleotide excision repair; base excision repair; DNA replication; homologous recombination; and complement and coagulation cascades. POLE, BUB1B, POLD4, C3, BLM, CCT7, PRPF31, APEX1, PSMA7, and CDC45 were chosen as hub genes after combining the PPI results. Our study recommends that BUB1B, CCT7, APEX1, PSMA7, and CDC45 might be potential biomarkers for gastric cancer. These biomarkers are upregulated genes. Therefore, suppression of these genes will increase the survival rate in gastric cancer patients.

Apigenin attenuates molecular, biochemical, and histopathological changes associated with renal impairments induced by gentamicin exposure in rats.

Gentamicin (GM) is an aminoglycoside antibiotic used to treat bacterial infections. However, its application is accompanied by renal impairments. Apigenin is a flavonoid found in many edible plants with potent therapeutic values. This study was designed to elucidate the therapeutic effects of apigenin on GM-induced nephrotoxicity. Animals were injected orally with three different doses of apigenin (5 mg kg-1 day-1, 10 mg kg-1 day-1, and 20 mg kg-1 day-1). Apigenin administration abolished the alterations in the kidney index and serum levels of kidney-specific functions markers, namely blood urea nitrogen and creatinine, and KIM-1, NGAL, and cystatin C following GM exposure. Additionally, apigenin increased levels of enzymatic (glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase) and non-enzymatic antioxidant proteins (reduced glutathione) and decreased levels of lipid peroxide, nitric oxide, and downregulated nitric oxide synthase-2 in the kidney tissue following GM administration. At the molecular scope, apigenin administration was found to upregulate the mRNA expression of Nfe2l2 and Hmox1 in the kidney tissue. Moreover, apigenin administration suppressed renal inflammation and apoptosis by decreasing levels of interleukin-1ß, tumor necrosis factor-alpha, nuclear factor kappa-B, Bax, and caspase-3, while increasing B-cell lymphoma-2 compared with those in GM-administered group. The recorded data suggests that apigenin treatment could be used to alleviate renal impairments associated with GM administration.

Ag NPs supported chitosan-agarose modified Fe3O4 nanocomposite catalyzed synthesis of indazolo[2,1-b]phthalazines and anticancer studies against liver and lung cancer cells.

In this article we report a novel Ag NPs fabricated chitosan-agarose composite functionalized core-shell type Fe3O4 nanoparticle (Ag/CS-Agar@Fe3O4). The biogenic material was analyzed over a number of physicochemical methods like, FT-IR, FE-SEM, TEM, EDX, XRD, VSM and ICP-OES. In catalytic exploration we aimed the synthesis of diverse 2H-indazolo0-b]phthalazine-trione derivatives via one-pot three component coupling of phathalalhydrazide, dimedone and different aldehydes. It afforded good to excellent yields under solvent-less conditions. Robustness of the catalyst was justified by catalyst recyclability for consecutive 10 times, hot filtration and leaching tests. Again, biological activity of the material was evaluated by studying the antioxidant and cytotoxicity properties over lung and liver cancer cell lines. Antioxidant potential of Ag/CS-Agar@Fe3O4 was assessed by DPPH radical scavenging studies and the corresponding IC50 was found to be 96.57 µg/mL. Liver and lung cancer studies over Ag/CS-Agar@Fe3O4 was carried out by MTT assay against HepG2 and A549 cell lines. The corresponding IC50 values were found as 192.35 and 365.28 µg/mL respectively. % Cell viability of the nanomaterial decreased dose dependently over both the cell lines without any cytotoxicity on normal cell line. The results demonstrates Ag/CS-Agar@Fe3O4 nanocomposite to be an efficient chemotherapeutic drug against the lung and hepatocellular carcinoma cells.

Antiulcer activity of proanthocyanidins is mediated via suppression of oxidative, inflammatory, and apoptotic machineries.

Gastric ulcer (GU) is a lesion in the gastric mucosa associated with excessive oxidative damage, inflammatory response, apoptotic events, and irritation which may develop into cancer. However, medications commonly used in GU treatment cannot normalize gastric mucosa, while causing several adverse effects. Proanthocyanidins (PAs) are dietary flavonoids with numerous biological and pharmacological activities. In the current investigation, we studied the potential anti-ulcerative activity of PAs against acidified ethanol (HCl/ethanol)-caused gastric ulceration. Fifty male albino Wistar rats were allocated into five equal groups: control, HCl/ethanol (3 mL/kg), lansoprazole (LPZ, 30 mg/kg) + HCl/ethanol, and PAs (100 and 250 mg/kg) + HCl/ethanol. LPZ and PAs were applied one week before gastric ulcer induction. PAs pretreatment notably reduced gastric mucosal macroscopic and microscopic pathological changes in a dose-dependent manner. Additionally, PAs activated the innate antioxidant molecules including glutathione and its derived antioxidants (glutathione peroxidase and glutathione reductase), along with superoxide dismutase and catalase, while attenuating pro-oxidant formation, including malondialdehyde and nitric oxide. Interestingly, PAs supplementation at a higher dose suppressed gastric inflammatory and apoptotic responses, as demonstrated by the reduced levels of interleukin-1ß, interleukin-6, tumor necrosis factor alpha, high-mobility group box 1, cyclooxygenase 2, prostaglandin E2, nuclear factor kappa-B, Bcl-2-associated X protein, and caspase-3, while B cell lymphoma 2 was elevated. Hence, PAs could exhibit antiulcer activity by protecting gastric tissue from the development of oxidative damage, inflammatory responses, and apoptosis events associated with ulceration. PRACTICAL IMPLICATIONS: Gastric ulcer is a lesion in the gastric mucosal layer associated with excessive inflammatory response, apoptotic events, oxidative damage, and irritation, and may develop into cancer with about 5%-10% morbidity rate. However, medications commonly used in GU treatment cannot normalize gastric mucosa, while causing several adverse effects. Therefore, new therapeutic approaches are needed to treat or prevent gastric ulceration. Proanthocyanidins (PAs, condensed tannins) are dietary flavonoids found in abundance in different plant species, including their fruits, bark, and seeds. Due to their potent antioxidative activity, PAs have been applied to prevent or treat oxidative stress-related diseases, including cancer, as well as metabolic, neurodegenerative, cardiovascular, and inflammatory disorders. Here, we examine the potential therapeutic role of proanthocyanidins (PAs) against acidified ethanol-induced gastric ulcer in rats through evaluating oxidative challenge, inflammatory response, apoptotic events, and histopathological changes in the gastric tissue.