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Natural biometabolites of plants have been reported to be useful in chronic diseases including diabetes and associated complications. This research is aimed to investigate how the biometabolites of

Nanotechnology is drawing attention nowadays due to its ability to regulate metals into nanosize, ultimately changing metal’s physical, chemical, and optical properties. Silver nanoparticles are known for their potential impact as antimicrobial agents due to their inherent property penetrating the cell wall. The present study aimed to develop and statistically optimise using a novel combination of capsaicin loaded silver nanoparticles (AgCNPs) as an effective anti-bacterial agent to treat psoriasis using a green approach. Ascorbic acid was used as a reducing agent to fabricate silver nanoparticles. The formulation parameters optimisation was conducted using Box-Behnken Design (3×3 factorial design). The loading of capsaicin was confirmed by attenuated total reflectance-fourier transform infrared spectroscopy. Energy-dispersive X-ray spectroscopy-scanning electron microscopy (EDX-SEM) confirmed the existence of silver; net-like structure revealed in SEM and high-resolution transmission electron microscopy further confirmed the nano size of the formulation. Differential scanning calorimetry and X-ray diffraction demonstrated the capsaicin transformed into amorphous after encapsulated. An in-vitro microbial study showed that the 0.10 M formulation of AgCNPs exerted potent anti-bacterial activity, which can be considered an alternative anti-bacterial agent. It also displayed that the zone of inhibition was significantly high in gram-negative bacteria (E. coli) than gram-positive bacteria (S. aureus). Green synthesised AgCNPs showed highly significant anti-bacterial activity, which indicates that this formulation can be very promising for treating psoriasis.

Pregabalin is one of a group of gabapentinoids approved by the Food and Drug Administration (FDA) in 2004. It is a capsule medication taken by mouth that is used for the treatment of neuropathic pain. It is a structural analogue of the neurotransmitter gamma-aminobutyric acid (GABA), and it appears to have a spectrum of benefits and harms similar to those of other adjuvant analgesics used to treat neuropathic pain. The most common side effects mentioned in peripheral neuropathy studies are dizziness and somnolence. Pregabalin could cause liver toxicity by increasing the levels of liver enzymes. It can potentially cause vasodilatation and fluid retention in the heart and blood vessels. It may also lead to addiction. The use of Pregabalin is common among patients with a history of substance abuse and psychoactive drug dependence, as euphoria is one of its main side effects. However, abrupt discontinuation from using Pregabalin may cause nausea, insomnia, or headache. The present review evaluates the significant impact of Pregabalin toxicity on liver and heart in patients and misusers. Keywords: Pregabalin, liver toxicity, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), heart failure, addiction.

The IL6/JAK2/STAT3 axis dysregulation and the related downstream pathways are a major contributor to the progression of non-small-cell lung carcinoma (NSCLC) and mainly affect apoptosis. Furthermor...

Graphical abstract, This research investigated the reno-protective effect of Thunbergia laurifolia Linn. (TL) in a lead-induced toxicity test through the modulation of cell signaling pathways. The study carried out to evaluate the effect of TL leaf extracts in Swiss Albino mice exposed to lead acetate (PbAc). Prior to in vivo study, a probable kidney-protective effect of the plant leaf extract was presumed through an activity-specific (PASS) molecular docking analysis. In animal model study, albino mice were divided in seven groups and co-treated with PbAc and TL (100, 200 mg/kgBW) or vitamin E (100 mg/kgBW) for 38 days, whereas the untreated control, TL control, and vehicle control groups received sodium acetate, PbAc, sodium acetate plus mineral oil, respectively. At the end of treatment, blood and kidney tissue were collected for investigating Pb concentration, estimating biochemical profile, evaluating oxidative stress and inflammatory parameters. The histopathological change of kidney along with apoptosis was assessed from kidney sections using H & E staining and TUNEL assay. Pb-exposed mice were found to be increased concentration of Pb in the blood and kidney sample, which further led to increased MDA levels in the plasma, blood, and tissue. Followed by kidney damage, increased expression of TNF-α, iNOS, and COX-2 in kidney tissues were noticed, which were related to elevated TNF-α in the systemic circulation of Pb-treated mice. Co-treatment with TL or vitamin E significantly reduced altered structure and apoptosis of kidney tissues. Downregulation of inflammatory markers especially TNF-α, iNOS, and COX-2 with simultaneous improvement of renal function through reduced plasma BUN and creatinine levels demonstrate that TL act as a potential dietary supplement to detoxify Pb in kidney showing an antioxidant and anti-inflammatory effect.

The current study investigated the immunomodulating and osteoblast differentiation potential of the natural compounds from Leea macrophylla (LMN). Immunomodulatory effects have been investigated by the phagocytosis of Candida albicans using polymorphonuclear neutrophil cells in the in vitro slide method. A bioactivity-guided fractionation technique was used to evaluate the stimulating effect of L. macrophylla methanol extract on osteoblast differentiation using mouse osteoblastic cells. A low dose of LMN was found to stimulate the phagocytic effect better than a higher dose. The natural compounds from L. macrophylla have significantly increased alkaline phosphatase (ALP) and osteocalcin activities. The LMN promoted the osteoblast differentiation through upregulation of ALP, osteocalcin, and type 1 collagen in a dose-dependent manner. These natural compounds also upregulated ALP, osteocalcin, and type 1 collagen gene expressions. The data suggest that LMN has potential anabolic sequel on bone formation and osteoblast differentiation.

This research investigated pharmacological properties mainly the anti-inflammatory, anthelmintic, thrombolytic and anxiolytic potential of methanol extract of Syzygium samarangense (MESS) var. parviflorum. Anti-inflammatory action by bovine serum albumin, egg albumin denaturation and membrane stabilization, anthelmintic by live parasites, thrombolytic by clot lysis and anxiolytic by elevated plus maze (EPM) and light and dark box (LDB) tests were measured. The four targeted pharmacological properties were further justified using the most prevalent compounds, isolated from this plant, to be undergone for their pharmacokinetic property’s analyses, sitemap analyses and lignad-receptor interactions by computational models through SwissADME and Schrödinger, 2018 softwares against PDB 6COX, 6D6T, 1JFF receptors. MESS was found to display statistically significant (P < 0.05) inhibition of Bovine Serum albumin and Egg albumin denaturation compared to reference drug diclofenac sodium. Remarkable vermicidal effect on the paralysis and death of anthelmintic parasites was observed at MESS concentration 200 mg/dL. A nondescript clot lysis of MESS compared to streptokinase was evident in in vitro thrombolytic assay. MESS increased the number of times the animal crossed from one compartment to the other and the time spent in the brightly-lit chamber of the LDB. Three-methylchalcone derivatives out of seven MESS compounds were undertaken, based on cut off value and sitemap prediction score, for further ligand-receptor binding efficiency. All these three compounds showed promising docking score, glide emodel and glide energy against PDB 6COX, 6D6T and 1DDJ, plasmin proteins demonstrating the prospects of MESS to be materialized for anti-inflammatory, anthelmintic, and thrombolytic therapeutics with further clarification.

Antipsychotics (APs) are widely used medications with reported diabetogenic side effects. This study investigated the effect of commonly used APs, namely chlorpromazine (CPZ), haloperidol (HAL) and clozapine, on the bioenergetics of male CD1 mice isolated pancreatic beta cells as an underlying mechanism of their diabetogenic effects. The effect of APs on Alamar blue reduction, adenosine triphosphate (ATP) production and glucose-stimulated insulin secretion (GSIS) of isolated beta cells was evaluated. Then, the effects of APs on the activities of mitochondrial complexes and their common coding genes expression, oxygen consumption rate (OCR), mitochondrial membrane potential (MMP) and lactate production were investigated. The effects of APs on the mitochondrial membrane fluidity (MMF) and mitochondrial membrane fatty acid composition were also examined. Results showed that the tested APs significantly decreased cellular ATP production and GSIS of the beta cells. The APs significantly inhibited the activities of mitochondrial complexes and their coding gene expression, MMP and OCR of the treated cells, with a parallel increase in lactate production to different extents with the different APs. CPZ and HAL showed increased MMF and mitochondrial membrane polyunsaturated fatty acid content. In conclusion, the tested APs-induced mitochondrial disruption can play a role in their diabetogenic side effect.

Objective This study investigated how a chemical-induced analgesia and inflammation could be managed by hot methanol extract of Leea macrophylla (Roxb.) root (LM). Methods Nature of secondary metabolites and the phytochemicals was studied by the established qualitative tests and GC-MS analysis. The analgesic potential was tested by acetic acid-induced writhing model, formalin test and tail immersion model. In contrast, carrageenan and histamine-induced paw edema models were applied to estimate the impact on inflammatogenic agents in Wistar albino rats. Results The LM was found to contain cardiac glycosides, flavonoids, tannins and triterpenoids. A list of about thirty compounds from the GC-MS study of LM has been recorded. The LM significantly (p Conclusion Results demonstrated that L. macrophylla (Roxb.) root extract could be very potential source of therapeutic formulation in pain and inflammation with further clarification.

Three benzimidazole derivatives, 1-(1H-benzimidazol-2-yl)ethanol (HBE), 1H-benzimidazol-2-yl(diphenyl)methanol (BDM) and 1,2-bis(1H-benzimidazol-2-yl)ethane-1,2-diol (BHBED), have been synthesized following the one-pot rapid green protocol. Complexes of benzimidazole derivatives with six 3d transition metals, Cu(II), Mn(II), Zn(II), Fe(II), Co(II), and Ni(II), have been synthesized by free hydrothermal method. The synthesized products have been characterized by FTIR, 1H, and 13C NMR, and mass spectroscopy, and CHN analysis, and 2:1 ligand to metal stoichiometry has been confirmed. The synthesized ligands and metal complexes have been tested for antioxidant potential (DPPH), inhibitory activity including inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), lipoxygenase (LOX), α-glucosidase. Micellar solubilization of the metal complexes has been studied in sodium dodecyl sulphate (SDS) by UV-Vis spectroscopy and conductivity. The selected complexes of nickel, zinc and cobalt have demonstrated interaction with SDS, and the value of critical micellar concentration increased in all cases.

A number of plant-derived drugs have been prescribed for treating atherothrombotic disorders such as myocardial or cerebral infarction. Therefore, this study investigated the individual and combined antithrombotic effects of six Asian plants on individuals with various BMIs. Venous blood drawn from healthy volunteers was allowed to form clots and treated with six organic fractions of Ophiorrhiza harrisiana Heyne, Haldina cordifolia (Roxb.) Ridsdale, Eclipta alba (L.) Hassk, Syzygium operculatum L., Lantana camara L., and Acanthus ilicifolius Linn. using the clot-lysis method. The weight of the clot before and after treatment provided the percentage of clot lysis. Variations in clot lysis in different BMI groups were assessed. A. ilicifolius induced the most thrombolytic activity, whereas L. camara showed slightly lower thrombolytic activity. The maximum clot-lysis activity was primarily observed in different fractions of O. harrisana, H. cordifolia, E. alba, S. operculatum, and A. ilicifolius. However, chloroform fractions of all plants except O. harrisana and L. camara showed maximum activity in individual plants. O. harrisana, H. cordifolia, E. alba, S. operculatum, L. camara, and A. ilicifolius showed the highest significant (P < 0.5 and P < 0.001) clotlysis activity viz., 46.60±0.79% (ethyl acetate), 55.40±1.023% (chloroform), 48.86±1.35% (CCl4 ), 44.89±1.76% (chloroform), 29.17±1.12% (ethanol), and 56.318±1.64% (chloroform). Obtained results were verified by ligandreceptor interaction through in silico approach. In conclusion, H. cordifolia, E. alba, and A. ilicifolius demonstrated promising thrombolytic effects; therefore, it is recommended that they be studied further for their therapeutic potential.

Background: The antiretroviral protease inhibitor drug lopinavir (LPV) is used to treat HIV-1 infection. LPV is known to have limited oral bioavailability, which may be attributed to its poor aqueous solubility, low efficacy and high first-pass metabolism. Self-nanoemulsifying drug delivery systems (SNEDDS) for LPV have been developed and optimised to counter the current issues. Methods: The titration method was used to prepare LPV-loaded SNEDDS (LPV-SNEDDS). Six different pseudo-ternary phase diagrams were constructed to identify the nanoemulsifying region. The developed formulations were chosen in terms of globule size < 100 nm, dispersity ≤ 0.5, dispersibility (Grade A) and % transmittance > 85. Heating-cooling cycle, freeze-thaw cycle, and centrifugation studies were performed to confirm the stability of the developed SNEDDS. Results: The final LPV-SNEDDS (L-14) droplet size was 58.18 ± 0.62 nm, with polydispersity index, zeta potential, and entrapment efficiency (EE%) values of 0.326 ± 0.005, -22.08 ± 1.2 mV, and 98.93 ± 1.18%, respectively. According to high-resolution transmission electron microscopy (HRTEM) analysis, the droplets in the optimised formulation were < 60 nm in size. The selected SNEDDS released nearly 99% of the LPV within 30 min, which was significantly (p < 0.05) higher than the LPV-suspension in methylcellulose (0.5% w/v). It indicates the potential use of SNEDDS to enhance the solubility of LPV, which eventually could help improve the oral bioavailability of LPV. The Caco-2 cellular uptake study showed a significantly (p < 0.05) higher LPV uptake from the SNEEDS (LPV-SNEDDS-L-14) than the free LPV (LPV-suspension). Conclusion: The LPV-SNEDDS could be a potential carrier for LPV oral delivery.

This project was supported by Researchers Supporting Project Number (RSP-2023R7) King Saud University, Riyadh, Saudi Arabia. S.A.C.C. acknowledges support from FCT/MCTES (Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through projects UIDB/50006/2020 and UIDP/50006/2020 and for the Scientific Employment Stimulus—Institutional Call (CEECINST/00102/2018). The authors thank The Islamia University of Bahawalpur for providing basic facilities. The degradation of dyes is a difficult task due to their persistent and stable nature; therefore, developing materials with desirable properties to degrade dyes is an important area of research. In the present study, we propose a simple, one-pot mechanochemical approach to synthesize CuO nanoparticles (NPs) using the leaf extract of Seriphidium oliverianum, as a reducing and stabilizing agent. The CuO NPs were characterized via X-ray diffraction (XRD), scanning electron microscopy (SEM), photoluminescence (PL) and Fourier-transform infrared spectroscopy (FTIR). The photocatalytic activity of CuO NPs was monitored using ultraviolet-visible (UV-Vis) spectroscopy. The CuO NPs exhibited high potential for the degradation of water-soluble industrial dyes. The degradation rates for methyl green (MG) and methyl orange (MO) were 65.231% ± 0.242 and 65.078% ± 0.392, respectively. Bio-mechanochemically synthesized CuO NPs proved to be good candidates for efficiently removing dyes from water publishersversion published

Diabetic nephropathy (DN) is a major risk factor for end-stage renal disease (ESRD). MicroRNAs (miRNAs/miRs) and their variants may be implicated in health and disease, including DN. The present study aimed to investigate the association of the miRNA-499a gene (MIR499A) A/G seed region variant (rs3746444) with DN-associated ESRD susceptibility in patients with diabetes mellitus, and to determine whether there was an association between the different genotypes and the patients' laboratory and clinical data. A case-control pilot study was conducted on 180 adult patients with type 2 diabetes mellitus. A total of 90 patients with ESRD on regular hemodialysis were considered as the cases, and 90 age-, sex- and ethnicity-matched diabetic patients with normo-albuminuria were considered as the controls. MIR499A genotyping was performed using a TaqMan Real-Time allele discrimination assay. Results demonstrated that the MIR499A rs3746444*G variant conferred susceptibility to the development of ESRD under co-dominant [(odds ratio (95% confidence interval): 2.49 (1.41-3.89) and 2.41 (1.61-6.68) for heterozygous and homozygous comparison, respectively], dominant [2.30 (1.18-3.90)] and allelic [1.82 (1.17-2.83)] models. Different genotypes of the specified variant did not exhibit significant associations with the clinic-laboratory data of the studied patients or the circulating miR-499a plasma levels. In conclusion, results of the present study suggested that MIR499A rs3746444 may be a susceptibility variant for DN-associated ESRD in the study population. However, larger sample size studies with different ethnicities are warranted to verify these findings.

Marine algae are ecologically important in the food chain and some of have demonstrated wide range of pharmacological properties including antidiabetic activities. This research was aimed to investigate the diabetes-healing effect of a phytochemically active marine alga Padina tenuis. Prior to the in vivo study, both qualitative and quantitative phytochemical status, acute toxicity and antioxidative effects by DPPH radical scavenging assay, ferric reducing assay, superoxide scavenging assay, iron chelating assay were evaluated. The in vivo study was conducted in 10% fructose-fed streptozotocin-induced diabetic rats categorized into five different groups including normal control (NC), diabetic control (DC), reference control (RC), treatments PT-25 (Padina tenuis chloroform extract 25 mg/kg b.w.) and PT-50. Upon routine observation on body weight, food intake, water intake, blood glucose, and oral glucose tolerance (OGT), the animals were sacrificed after three weeks of intervention. Organ weights, serum lipid profile, insulin, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), creatinine, uric acid and urea were calculated as major indices. The results showed very promising phenolic and flavonoid content, substantial antioxidative effect, non-toxicity in acute level and strong α-amylase inhibition. PT-25 was found to significantly manage the serum AST, ALP, creatinine, uric acid, weekly blood glucose level, glucose tolerance ability as well as kidney and pancreatic weights. Moreover, kidney and pancreatic architecture in histopathological screening were notably improved in the treatment group. β-cells/islet of Langerhans and kidney cells were improved compared to NC animals. The data suggests that Padina tenuis could be very effective as natural sources of antidiabetic agents to modulate pancreatic action and kidney function.

In the present study, naphthyl acetohydrazide (HL) ligand was prepared and used for the synthesis of new six amorphous transition metal (Co(II), Ni(II), Cu(II), Zn(II), Pb(II), Cd(II)) complexes. All the compounds were characterized by elemental analysis, UV-vis, FT-IR, 1H- and 13C-NMR, and Matrix-Assisted Laser Desorption Ionization (MALDI). The solubilization study was carried out by estimating the interaction between the metal complexes with surfactants viz. sodium stearate (SS) and Cetyltrimethylammonium bromide (CTAB). UV-Visible spectroscopy was employed to determine partitioning and binding parameters, whereas electrical conductivity measurements were employed to estimate critical micellar concentration (CMC), the extent of dissociation, and free energy of micellization. The CT-DNA interaction of synthesized compounds with DNA represents the major groove binding. The synthesized ligand and metal complexes were also tested against bacterial and fungal strains and it has been observed that Cu(II) complex is active against all the strains except Candida albicans, while Cd(II) complex is active against all bacterial and fungal strains except Pseudomonas. Among all compounds, only the Pd(II) complex shows reasonable activity against cervical cancer HeLa cell lines, representing 97% inhibition.

COVID-19 is considered as the most challenging in the current situation but lung cancer is also the leading cause of death in the global population. These two malignancies are among the leading human diseases and are highly complex in terms of diagnostic and therapeutic approaches as well as the most frequent and highly complex and heterogeneous in nature. Based on the latest update, it is known that the patients suffering from lung cancer, are considered to be significantly at higher risk of COVID-19 infection in terms of survival and there are a number of evidences which support the hypothesis that these diseases may share the same functions and functional components. Multi-level unwanted alterations such as (epi-)genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major sources which promote a number of complex diseases and such heterogeneous level of complexities are considered as the major barrier in the development of therapeutics. With so many challenges, it is critical to understand the relationships and the common shared aberrations between them which is difficult to unravel and understand. A simple approach has been applied for this study where differential gene expression analysis, pathway enrichment, and network level understanding are carried out. Since, gene expression changes and genomic alterations are related to the COVID-19 and lung cancer but their pattern varies significantly. Based on the recent studies, it appears that the patients suffering from lung cancer and and simultaneously infected with COVID-19, then survival chance is lessened. So, we have designed our goal to understand the genes commonly overexpressed and commonly enriched pathways in case of COVID-19 and lung cancer. For this purpose, we have presented the summarized review of the previous works where the pathogenesis of lung cancer and COVID-19 infection have been focused and we have also presented the new finding of our analysis. So, this work not only presents the review work but also the research work. This review and research study leads to the conclusion that growth promoting pathways (EGFR, Ras, and PI3K), growth inhibitory pathways (p53 and STK11), apoptotic pathways (Bcl- 2/Bax/Fas), and DDR pathways and genes are commonly and dominantly altered in both the cases COVID-19 and lung cancer.

The IL6/JAK2/STAT3 axis dysregulation and the related downstream pathways are a major contributor to the progression of non-small-cell lung carcinoma (NSCLC) and mainly affect apoptosis. Furthermore, tubulin inhibitors are potential chemotherapeutic agents against NSCLC. In this study, we have provided new molecular insights into the antiproliferative activity of six 3β-acetoxy-5α-androstane heterocycle compounds against NSCLC. The cell line A549, which represents a good model of NSCLC, was used to evaluate the antitumour activity of tested androstane derivatives, and non-cancerous gingival mesenchymal stem cell line (GMSC) were used to assess the specificity and toxicity of the tested compounds. Further on, molecular docking predictions were used to determine the molecular targets for the most promising cytotoxic compound. To assess apoptosis and cell cycle progression in treated A549 cells, flow cytometry was used. RT-qPCR and ELISA analyses were used to gain deep insights into cellular and molecular mechanisms. Results revealed that compound

The hydrazone derived ketimine of dehydroacetic acid and its metal {Cu(II), Ni(II), Zn(II), Fe(III), Cd(II), Pd(II), La(III), Nd(III), Ce(III)} complexes are synthesized and characterized by IR, 1H and 13C NMR, and UV-Vis spectroscopy. DNA studies have been carried out for metal complexes by electronic absorption spectroscopy. It is determined that metal complexes bind to DNA through intercalation. The complexes of Cu(II), Zn(II) and Pd(II) demonstrate significant activity against HeLa cells (cervical cancer).

Carbamazepine (CBZ) is a widely employed anti-seizure medication that crosses the blood-brain barrier (BBB) to exert its anti-convulsant action. The effects of CBZ on components of the BBB have yet to be completely delineated. Hence the current study evaluated the effects of CBZ upon mitochondrial functionality of BBB-derived microvascular endothelial cells isolated from Albino rats. The influence of CBZ on cell viability and barrier functions were evaluated by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), lactate dehydrogenase, and electrophysiological assays over a drug concentration range of 0.1–1000 μM. Bioenergetics effects were measured via ATP production, mitochondrial complexes I and III activities, lactate production, and oxygen consumption rates (OCRs), and mitochondrial membrane potential, fluidity and lipid content. CBZ was cytotoxic to microvascular endothelial cells in a concentration and duration dependent manner. CBZ significantly diminished the endothelial cell’s barrier functions, and impacted upon cellular bioenergetics: reducing mitochondrial complex activities with a parallel decrease in OCRs and increased anaerobic lactate production. CBZ significantly decreased mitochondrial membrane potential and induced an increase of membrane fluidity and decrease in levels of mitochondrial saturated and unsaturated fatty acids. In summary, CBZ disrupted functional activity of BBB endothelial cells via damage and modification of mitochondria functionality at therapeutically relevant concentrations.

The straight forwarded new green approach to the synthesis of N-phenyl benzamidine derivatives catalyzed by copper oxide nanoparticles (CuOnp) under solvent-free conditions (without microwave radiations and with MW radiation) is presented. All synthesized compounds 3a–3k are characterized by FT-IR, NMR, and single crystal XRD analysis and tested for their antioxidant and elastase inhibition activities. The compounds 3i and 3j demonstrate significant free radical scavenging activity. The accumulated data indicate that some synthesized compounds can be recognized as good anti-aging agents.

Degranulation of mast cells and basophils occurs after the cross-linking of FceRI receptor-bound IgE by multivalent allergens, resulting in the release of a range of de novo synthesized and preformed mediators of the allergic response. β-Hexosaminidase release is usually measured as a simple readout for degranulation. Furthermore, the rat basophilic leukemia (RBL)-2H3 cell line is commonly used for measuring degranulation, monitoring β-hexosaminidase release. Here, we describe surface-engineered and modified nanoparticles with specific ligands in order to study the signaling and cellular responses of the RBL-2H3 cell line.

The cancer-brake gene CTLA4 has a vital function in suppressing the immune responses of activated T lymphocytes. Numerous reports explored the impact of various CTLA4 variants with the predisposition for malignancies but with unconvincing findings. Hence, this study is designed to assess the association of CTLA4 (c.49AG, rs231775) variant with the outcome of breast carcinoma. A total of 272 participants (93 BC patients and 179 cancer-free healthy volunteers) were enrolled. Genomic DNA for all participants was genotyped for CTLA4 (c.49AG) variant via TaqMan genotyping assay. Patients with A/G genotype conferred protection against developing BC under heterozygote comparison (OR = 0.56, 95%CI = 0.31-0.98) as well dominant model (OR = 0.55, 95%CI = 0.32-0.97). AG/GG genotypes were anchored with an increased risk of nodal infiltration (OR = 2.90, 95%CI = 1.03-8.17, P = 0.037), metastasis (OR = 4.46, 95%CI = 1.18-16.8, P = 0.019), advanced clinical stage (OR = 6.54, 95%CI = 2.06-20.75, P 0.001), recurrence (OR = 5.2, 95%CI = 1.73-15.7, P = 0.001), and shorter survival (OR = 2.54, 95%CI = 1.08-5.99, P = 0.032). In addition, functional enrichment analysis revealed the key role of CTLA4 in cancer immunosurveillance. Our findings indicated that the CTLA4 c.49AG variant might have prognostic as well diagnostic impact in breast cancer.

Background: Emerging evidence indicates group-specific component (GC) variants are associated with ethnicity. We aimed to investigate the association of GC variants and protein expression level wit...

In addition to the diverse applications of chelation in catalysis, material synthesis and photochemistry, chelation displayed in biological systems enables metals to attach with or to move away from the susceptible target owing to to ease or hampering those intracellular connections which might finally lead to cancer

Worldwide, cancer is still an area with high unmet medical need. Lead optimization efforts towards structure-based drug design were employed to discover newly synthesized hetero-steroid derivatives with promising anticancer effects against hepatocellular carcinoma (HCC). The aim of our study is to evaluate the anti-proliferative activity and the mechanism, a dual PI3K/mTOR inhibitor, and mechanism of action of a series of heterocylic androstane derivatives as anti-HCC agent. The cytotoxic effects of different heterocylic androstanes and 5FU as single agents, were assessed against both HepG2 cells and Non-malignant MDCK cell line to assess the toxicity. Then the underlying mechanism of compound 4 as most promising compound was evaluated using molecular docking, MTT assay, cell cycle analysis, DNA fragmentation, and real-time PCR. The results of MTT assay showed potential cytotoxic effect for compound 4 and 5 against liver cancer cell line with IC50 value 39.81 and 57.54 μM, respectively. Inhibition of the PI3K/AKT/mTOR pathway was achieved by compound 4, which was documented by molecular docking and augmented by gene expression analysis. Detailed mechanism revealed that compound 4 induced cell cycle arrest, DNA fragmentation, and induction of apoptosis by inhibition of anti-apoptotic genes, and upregulation of apoptotic genes. Our results shed a light on aminopyrazoloandrostane derivative 4 as an inhibitor of the PI3K/AKT/mTOR pathway, which might be acting as promising anti-liver cancer agent. Our data support further investigation of agents targeting the PI3K/AKT/mTOR.