Studies on the ameliorative potential of Rheum webbianum rhizome extracts on 1,2-dimethylhydrazine (DMH) induced colorectal cancer and associated hepatic and haematological abnormalities in swiss albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheum webbianum Royle (RW) holds significant ethnopharmacological importance owing to its 5000-year history of cultivation for medicinal and culinary purposes. Demonstrating therapeutic advantages in traditional and contemporary medical practices, RW exhibits key pharmacological effects including anticancer activity, gastrointestinal control, anti-inflammatory properties, and suppression of fibrosis. Despite its recognized vast bioactivities in ethnopharmacology, its efficacy against the colorectal cancer (CRC) remains incompletely understood. AIM OF THE STUDY: This study for the first time aims to investigate the chemo-preventive capabilities of various extracts derived from RW rhizomes against CRC development. MATERIALS AND METHODS: Four types of RW extracts were prepared by using different solvents viz: Hexane, Ethy-acetate, Ethanol and Methanol. All the four extracts were evaluated for cytotoxicity on HCT-116 human CRC cells. Promising extracts were further investigated in-vivo at varying doses using 1,2-dimethylhydrazine (DMH) induced rat CRC model to assess the anti-oxidant and anticancer properties as well as their effects on the associated hepatic deterioration and hematological alterations. RESULTS: Cell viability: In-vitro assessments demonstrated a dose and time-dependent reduction in HCT-116 cell viability following treatment with methanolic and ethanolic extracts of RW, reducing viability by up to 85% and 90%, respectively, at 200 µg/ml. HISTOPATHOLOGY: Histopathological analyses revealed significant improvements in colon tissue morphology in RW extract-treated groups compared to DMH-only treated animals. RW-treated groups showed reduced structural abnormalities, congestion, inflammatory cell infiltration, crypt abscess formation, and dysplasia. In contrast, the DMH-only group exhibited irregular glandular structure, mucosal destruction, extensive inflammatory cell infiltration, crypt abscess formation, and dysplasia. These results highlight the potential of RW methanolic and ethanolic extracts in mitigating colon cancer-related histopathological alterations. Haematological, and hepatic parameters: In the DMH-induced colorectal cancer rat model, significant hematological imbalances were evident, including a 49.13% decrease in erythrocytes, 32.18% in hemoglobin, and 26.79% in hematocrit, along with a 79.62% increase in white blood cells and 68.96% rise in platelets. Administration of RW rhizome extracts effectively restored these hematological parameters to levels comparable to those in the control group. Furthermore, RW treatment significantly reduced serum ALT and AST levels, which had increased by 36.78% and 33.12%, respectively, due to DMH exposure. RW intervention also mitigated the onset of atherosclerosis, evidenced by notable reductions in serum total cholesterol and triglyceride levels. Comparative analysis indicated that RW-treated DMH groups effectively restored lipid profiles, contrasting with the DMH-only group which exhibited markers indicative of colon cancer. Oxidative stress: The DMH-treated group showed a significant increase in MDA levels by 195.59%, indicative of heightened free radical production, coupled with decreased levels of SOD (33%), CAT (48%), GSH (58%), and GR activity (49%), signifying oxidative stress. Treatment with RW extracts in DMH-treated rats markedly reduced MDA levels and enhanced SOD, CAT, GSH, and GR activities. These results underscore the antioxidant efficacy of RW extracts. CONCLUSION: This study underscores the significant potential of RW rhizome extracts in inhibiting colorectal cancer development. Further investigations are warranted to identify the active constituents responsible for these promising outcomes, positioning RW as a natural and potential agent in combating colon cancer.

Suberosin Alleviates Thiazolidinedione-Induced Cardiomyopathy in Diabetic Rats by Inhibiting Ferroptosis via Modulation of ACSL4-LPCAT3 and PI3K-AKT Signaling Pathways.

Thiazolidinediones are useful antidiabetic medications. However, their use is associated with adverse side effects like edema, heart failure and bone fractures. In this study, we investigated the anti-ferroptosis effects of suberosin (SBR; a prenylated coumarin) in diabetic Sprague Dawley rats. Further, we assessed the effects of co-administration of SBR (30 and 90 mg/kg/day) with thiazolidinedione (TZ at 15 mg/kg) to mitigate TZ-induced cardiomyopathy in diabetic rats. Our results showed that cardiac output, stroke volume, left ventricle systolic and diastolic pressures were aggravated in diabetic rats treated with TZ alone after 4 weeks. TZ treatments induced ferroptosis as well as marked histoarchitecture disarrangements in rat cardiomyocytes. The study found that optimizing volume overload alleviated cardiac hypertrophy and mitigated left ventricular dysfunction in diabetic rats co-treated with SBR. SBR co-administration with TZ reduced MDA levels in heart tissue and serum iron concentration (biomarkers of ferroptosis), downregulated mRNA expressions of LOX, ACSL4, LPCAT3, and promoted GPX4 activity as well as upregulated mRNA levels of AKT/PI3K/GSK3ß as compared to the group administered with TZ at 15 mg/kg. SBR co-administration also helped to retain the normal histoarchitecture of cardiomyocytes in diabetic rats. Hence, our results suggested that SBR is an effective supplement and could be prescribed to diabetic patients along with TZ but this requires further clinical trials.

Dissecting the Role of SMYD2 and Its Inhibitor (LLY-507) in the Treatment of Chemically Induced Non-Small Cell Lung Cancer (NSCLC) by Using Fe3O4 Nanoparticles Drug Delivery System.

Cancer therapies based on nanoparticles with a loaded drug can overcome the problem of the drug's toxic effects in the traditional chemotherapeutic approach. In this study, we loaded LLY-507, a potent inhibitor of SMYD2, a methyltransferase enzyme, on iron oxide nanoparticles (IONPs). The prepared nanoparticles were characterized by microscopic analysis, loading efficiency, and drug release studies. Microscopic examination revealed an average grain size of 44 nm. The in vitro effect of LLY-507-IONPs, LLY-507, and IONPs was determined by MTT analysis (A549 cells) and hemolysis studies. IONPs have almost negative hemolytic activity in blood. The cell viability assay revealed IC50 values of both LLY-507 alone and LLY-507-loaded IONPs against A549; the lower value of the drug loaded on NPs (0.71 µg/mL alone and 0.53 µg/mL loaded on NPs) shows strong synergistic anticancer potential. We further tested the role of loaded NPs in a urethane-induced lung cancer mouse model (n = 40 mice in three independent trials, 20 mice in control group) to check the role of SMYD2 at various time points of lung cancer development. The loss of SMYD2 due to LLY-507 suppressed tumor growth, emphysema, hemorrhage, and congestion considerably. Hence, it can be concluded that the SMYD2 inhibitor has an anti-inflammatory effect on the mouse lung and suppresses tumor growth by inhibiting the SMYD2 protein.

Synthesis and characterization of Guar gum based biopolymeric hydrogels as carrier materials for controlled delivery of methotrexate to treat colon cancer.

Guar Gum has been evaluated for its importance in food and pharmaceutical industry. A blended biopolymeric hydrogel was prepared by solution casting technique using guar gum (GG), chitosan (CS), polyvinyl alcohol (PVA), chemically crosslinked with tetra orthosilicate (TEOS) and impregnated with methotrexate (MTX) to assess its drug carrying capacity against colon cancer (HCT-116). The surface morphology, chemical bonding, hydrophilicity and water absorbing capacity were analyzed by atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), contact angle measurements and swelling properties in variable conditions. Furthermore, degradation, drug release kinetics, hemocompatibility, and cytotoxicity of MTX-loaded hydrogel was tested. The release of MTX from GG/CS/PVA biopolymeric blend occurred in sustained manner. Results displayed that in 7 h 25 min duration 96% of the drug was released in phosphate buffer saline (PBS) at pH 7.4. These blends were non-hemolytic, and antiproliferative against HCT-116. Furthermore, the MTT assay has revealed that MTX-loaded hydrogel had prominently decreased the cell viability (with IC50 11.7 µg/ml) as compared to free MTX (with IC50 21.57 µg/ml). Hence, these results suggest that guar gum based hydrogels are potential biomaterials for colon cancer treatment.

Anti-EMT properties of ergothioneine attenuate lipopolysaccharide-induced oxidative stress-mediated acute lung injury via modulating TGF-ß/smad/snail signaling pathway.

Acute lung injury (ALI) is a heterogeneous pulmonary illness that is fast developing and has a high fatality rate. The current investigation set out to interpret the convergence of oxidative stress, inflammatory cytokines, TNF-α, snail, vimentin, e-cadherin, and NF-kB activation in ALI pathology. The outcome of assays of oxidative stress, ELISA, and western blot showed the declined of CAT, SOD, GPx, IL-1ß, TNF-α, and upregulation of TGF-ß, smad2/3, smad4, NF-kB, snail, and vimentin, concurrently with downregulation of e-cadherin expression in lung tissues as well as BALF in LPS-injected rats. The photomicrographs of the lungs marked severe congestion, infiltration of cytokines, and thickening of the alveolar walls. Pretreatments of ergothioneine after LPS-induced ALI, inhibited EMT-induction by blocking TGF-ß, smad2/3, smad4, snail, vimentin, NF-kB, and inflammatory cytokines, and increased the expression of E-cadherin and antioxidant levels in a dose-dependent manner. These events helped to restore lung histoarchitecture and reduce acute lung injury. The present findings suggest that ergothioneine at 100 mg/kg is as effective as febuxostat (reference drug). The study concluded that ergothioneine may be replaced with febuxostat as a treatment option for ALI owing to its side effects after clinical trials for pharmaceutical purposes.

Bioinspired engineered nickel nanoparticles with multifunctional attributes for reproductive toxicity.

Nickel nanoparticles (Ni-NPs) have potential applications in high-tech sectors such as battery manufacturing, catalysis, nanotube printing and textile. Apart from their increasing utilisation in daily life, there are concerns about their hazardous nature as they are highly penetrable in biological systems. The carcinogenic and mutagenic ability of Ni-NPs is evident but the research gaps are still there concerning the safety evaluation of Ni-NPs regarding male reproductive ability. This controlled randomized research was planned to assess the male reproductive toxicity of Ni-NPs in Sprague Dawley rats. Ni-NPs of spherical shape and mean particle size of 56 nm were used in the study, characterized by SEM, EDS and XRD. The twenty-five healthy rats (200-220 g) were used for toxicity investigation of Ni-NPs and divided into five groups; negative control (0 Ni-NPs), placebo group (0.9% saline) and three Ni-NPs treated groups (@ 15, 30 and 45 mg/kg BW). The results of 14 days of intraperitoneal exposure to Ni-NPs revealed that a higher dose (45 mg/kg BW) of Ni-NPs caused a significant reduction in body weight, serum testosterone, daily sperm production while the testis index and Ni accumulation and histological changes (necrosis in basement membrane and seminiferous tubules, vacuole formation) in testicular tissues increased with increasing dose of Ni-NPs. It can be concluded from the study that Ni-NPs have potential reproductive toxicity. This study provided the baseline data of Ni-NPs toxicity for the male reproductive system and can be applied for risk assessment in Ni-NPs based products.

Identification of Natural Compounds as Inhibitors of Pyruvate Kinase M2 for Cancer Treatment.

The reliance of tumor cells on aerobic glycolysis is one of the emerging hallmarks of cancer. Pyruvate kinase M2 (PKM2), an important enzyme of glycolytic pathway, is highly expressed in a number of cancer cells. Tumor cells heavily depend on PKM2 to fulfill their divergent energetic and biosynthetic requirements, suggesting it as novel drug target for cancer therapies. Based on this context, we performed enzymatic-assay-based screening of the in-house phenolic compounds library for the identification of PKM2 inhibitors. This screening identified silibinin, curcumin, resveratrol, and ellagic acid as potential inhibitors of PKM2 with IC50 values of 0.91 µM, 1.12 µM, 3.07 µM, and 4.20 µM respectively. For the determination of Ki constants and the inhibition type of hit compounds, Lineweaver-Burk graphs were plotted. Silibinin and ellagic acid performed the competitive inhibition of PKM2 with Ki constants of 0.61 µM and 5.06 µM, while curcumin and resveratrol were identified as non-competitive inhibitors of PKM2 with Ki constants of 1.20 µM and 7.34 µM. The in silico screening of phenolic compounds against three binding sites of PKM2 provided insight into the binding pattern and functionally important amino residues of PKM2. Further, the evaluation of cytotoxicity via MTT assay demonstrated ellagic acid as potent inhibitor of cancer cell growth (IC50 = 20 µM). These results present ellagic acid, silibinin, curcumin, and resveratrol as inhibitors of PKM2 to interrogate metabolic reprogramming in cancer cells. This study has also provided the foundation for further research to validate the potential of identified bioactive entities for PKM2 targeted-cancer therapies.

Ameliorative Hematological and Histomorphological Effects of Dietary Trigonella foenum-graecum Seeds in Common Carp (Cyprinus carpio) Exposed to Copper Oxide Nanoparticles.

Different types of metal oxide nanoparticles (NPs) are being used for wastewater treatment worldwide but concerns have been raised regarding their potential toxicities, especially toward non-targeted aquatic organisms including fishes. Therefore, the present study aimed to evaluate the toxicity of copper oxide (CuO) NPs (1.5 mg/L; positive control group) in a total of 130 common carp (Cyprinus carpio), as well as the potential ameliorative effects of fenugreek (Trigonella foenum-graecum) seed extracts (100 mg/L as G-1 group, 125 mg/L as G-2 group, and 150 mg/L as G-3 group) administered to fish for 28 days. Significant changes were observed in the morphometric parameters: the body weight and length of the CuO-NP-treated fish respectively decreased from 45.28 ± 0.34 g and 14.40 ± 0.56 cm at day one to 43.75 ± 0.41 g and 13.57 ± 0.67 cm at day 28. Conversely, fish treated with T. foenum-graecum seed extract showed significant improvements in body weight and length. After exposure to CuO NPs, a significant accumulation of Cu was recorded in the gills, livers, and kidneys (1.18 ± 0.006 µg/kg ww, 1.38 ± 0.006 µg/kg ww, and 0.05 ± 0.006 µg/kg ww, respectively) of the exposed common carp, and significant alterations in fish hematological parameters and oxidative stress biomarkers (lipid peroxidation (LPO), glutathione (GSH), and catalase (CAT)) were also observed. However, supplementing diets with fenugreek extracts modulated the blood parameters and the oxidative stress enzymes. Similarly, histological observations revealed that sub-lethal exposure to CuO NPs caused severe histomorphological changes in fish gills (i.e., degenerative epithelium, fused lamellae, necrotic lamellae, necrosis of primary lamellae, complete degeneration, and complete lamellar fusion), liver (i.e., degenerative hepatocytes, vacuolization, damaged central vein, dilated sinusoid, vacuolated degeneration, and complete degeneration), and kidney (i.e., necrosis and tubular degeneration, abnormal glomerulus, swollen tubules, and complete degeneration), while the treatment with the fenugreek extract significantly decreased tissue damage in a dose-dependent manner by lowering the accumulation of Cu in the selected fish tissues. Overall, this work demonstrated the ameliorative effects of dietary supplementation with T. foenum-graecum seed extract against the toxicity of NPs in aquatic organisms. The findings of this study therefore provided evidence of the promising nutraceutical value of fenugreek and enhanced its applicative potential in the sector of fish aquaculture, as it was shown to improve the growth performance and wellness of organisms.

Identification of Novel Natural Inhibitors to Human 3-Phosphoglycerate Dehydrogenase (PHGDH) for Cancer Treatment.

Targeting the serine biosynthesis pathway enzymes has turned up as a novel strategy for anti-cancer therapeutics. 3- Phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme that catalyzes the conversion of 3-Phosphoglyceric acid (3-PG) into 3-Phosphohydroxy pyruvate (3-PPyr) in the first step of serine synthesis pathway and perform a critical role in cancer progression. PHGDH has been reported to be overexpressed in different types of cancers and emerged as a novel target for cancer therapeutics. During this study, virtual screening tools were used for the identification of inhibitors of PHGDH. A library of phenolic compounds was docked against two binding sites of PHGDH using Molegro Virtual Docker (MVD) software. Out of 169 virtually tested compounds, Salvianolic acid C and Schizotenuin F possess good binding potential to co-factor binding site of PHGDH while Salvianolic acid I and Chicoric acid were identified as the best binding compounds toward the substrate binding site of PHGDH. The top selected compounds were evaluated for different physiochemical and ADMET properties, the obtained results showed that none of these hit compounds violated the Pfizer Rule and they possess acceptable ADMET profiles. Further, a commercially available hit compound, Chicoric acid, was evaluated for its anti-cancer potential against PHGDH-expressing gastric cancer cell lines (MGC-803 and SGC-7901) as well as cell lines with low expression of PHGDH (MCF-7 and MDA-MB2-31), which demonstrated that Chicoric acid possesses selective cytotoxicity toward PHGDH expressing cancer cell lines. Thus, this study has unveiled the potential of phenolic compounds, which could serve as novel candidates for the development of PHGDH inhibitors as anti-cancer agents.

Identification of Macrolepiota procera extract as a novel G6PD inhibitor for the treatment of lung cancer.

Tumor metabolism, an emerging hallmark of cancer, is characterized by aberrant expression of enzymes from various metabolic pathways including glycolysis and PPP (pentose phosphate pathway). Glucose 6 phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD), oxidative carboxylases of PPP, have been reported to accomplish different biosynthetic and energy requirements of cancer cells. G6PD and 6PGD have been proposed as potential therapeutic targets for cancer therapy during recent years due to their overexpression in various cancers. Here, we have employed enzymatic assay based screening using in-house G6PD and 6PGD assay protocols for the identification of mushroom extracts which could inhibit G6PD or 6PGD enzymatic activity for implications in cancer therapy. For the fulfillment of the objectives of present study, nine edible mushrooms were subjected to green extraction for preparation of ethanolic extracts. 6xhis-G6PD and pET-28a-h6PGD plasmids were expressed in BL21-DE3 E. coli cells for the expression and purification of protein of interests. Using purified proteins, in house enzymatic assay protocols were established. The preliminary screening identified two extracts (Macrolepiota procera and Terfezia boudieri) as potent and selective G6PD inhibitors, while no extract was found highly active against 6PGD. Further, evaluation of anticancer potential of mushroom extracts against lung cancer cells revealed Macrolepiota procera as potential inhibitor of cancer cell proliferation with IC50 value of 6.18 µg/ml. Finally, screening of M. procera-derived compounds against G6PD via molecular docking has identified paraben, quercetin and syringic acid as virtual hit compounds possessing good binding affinity with G6PD. The result of present study provides novel findings for possible mechanism of action of M. procera extract against A549 via G6PD inhibition suggesting that M. procera might be of therapeutic interest for lung cancer treatment.

A Review on Phyto-pharmacology of Oxalis corniculata.

Oxalis corniculata (Oxalidaceae) is a small decumbent and delicate appearing medicinal herb flourishing in warm temperate and tropical domains such as Pakistan and India. Main bioactive chemical constituents of Oxalis plant include several alkaloids, flavonoids, terpenoids, cardiac glycosides, saponins, and phlobatannins, along with steroids. Due to its polyphenolic, glycosides and flavonoid profile, it is proved to be protective in numerous ailments and exhibit various biological activities such as anti-fungal, anti-cancer, anti-oxidant, antibacterial, anti-diabetic, and cardioprotective. Moreover, bioactive phytochemicals from this plant possess significant wound healing potential. Our current effort intends to emphasize on the immense significance of this plant species, which have not been the subject matter of clinical trials and effective pharmacological studies, even though its favored usage has been stated. This review proposes that Oxalis corniculata possess a potential for the cure of various diseases. However, further researches on isolation and characterization of bioactive compounds along with pre-clinical trials are compulsory to figure out its pharmacological applications.

Toxicity assessment of metallic nickel nanoparticles in various biological models: An interplay of reactive oxygen species, oxidative stress, and apoptosis.

Nickel nanoparticles (Ni-NPs) are widely used for multiple purposes in industries. Ni-NPs exposure is detrimental to ecosystems owing to widespread use, and so their toxicity is important to consider for real-world applications. This review mainly focuses on the notable pathophysiological activities of Ni-NPs in various research models. Ni-NPs are stated to be more toxic than bulk forms because of their larger surface area to volume ratio and are reported to provoke toxicity through reactive oxygen species generation, which leads to the upregulation of nuclear factor-κB and promotes further signaling cascades. Ni-NPs may contribute to provoking oxidative stress and apoptosis. Hypoxia-inducible factor 1α and mitogen-activated protein kinases pathways are involved in Ni-NPs associated toxicity. Ni-NPs trigger the transcription factors p-p38, p-JNK, p-ERK1/2, interleukin (IL)-3, TNF-α, IL-13, Fas, Cyt c, Bax, Bid protein, caspase-3, caspase-8, and caspase-9. Moreover, Ni-NPs have an occupational vulnerability and were reported to induce lung-related disorders owing to inhalation. Ni-NPs may cause serious effects on reproduction as Ni-NPs induced deleterious effects on reproductive cells (sperm and eggs) in animal models and provoked hormonal alteration. However, recent studies have provided limited knowledge regarding the important checkpoints of signaling pathways and less focused on the toxic limitation of Ni-NPs in humans, which therefore needs to be further investigated.

Nickel nanoparticles induce hepatotoxicity via oxidative and nitrative stress-mediated apoptosis and inflammation.

Nickel nanoparticles (Ni NPs) are utilized extensively in various industrial applications. However, there are increasing concerns about potential exposure to Ni NPs and consequent health effects. The aim of this study was to assess Ni NPs-induced liver toxicity in Sprague Dawley rats. Twenty-five rats were exposed to Ni NPs via intraperitoneal injection at doses of 15, 30, and 45 mg/kg per body weight for 28 days. Results from ICP-MS analysis showed an increase in the concentration of Ni NPs in a dose-dependent manner. The liver dysfunction was indicated by considerable production of ALT, AST, ALP, LDH, and TB in Ni NPs-treated rats. Histological examination demonstrated liver injuries (inflammatory cells, congestion, necrosis, and pyknosis) in exposed rats with dose-dependent severity of pathologies by semi-quantitative histograding system. To explore the toxicological pathways, we examined oxidative stress biomarkers and detected Ni NPs significantly elevated the levels of MDA and LPO while decreasing the levels of CAT and GSH. All the changes in biomarkers were recorded in a dose-dependent relationship. In addition, we found upregulated NF-kß indicating activation of inflammatory cytokines. ELISA results of serum revealed a remarkable increase of nitrative stress markers (iNOS and NO), ATPase activity, inflammatory cytokine (IL-6, IL-1ß, and TNF-α), and apoptotic mediators (caspase-3 and caspase-9) in Ni NPs-treated groups than the control. In summary, the result of this study provided evidence of hepatotoxicity of Ni NPs and insightful information about the involved toxic pathways, which will help in health risk assessment and management, related preventive measures for the use of Ni-NPs materials.

Comparative efficacy of Ovaprim and hMG (menotropin) to induce breeding in African catfish (Clarias gariepinus).

The applications of exogenous hormones in different species for the induction of oocyte production, final oocyte maturation (FOM), and spawning for their reproduction is getting more attention day by day. The current preliminary research work was carried out to induce breeding in Clarias gariepinus, commonly known as African catfish, imported from Thailand. Single doses of two hormones as Ovaprim and human menopausal gonadotropin (hMG) were used and the research work was carried out at Muzaffargarh Fish Hatchery Punjab, Pakistan. A total of twenty-four (n = 24) C. gariepinus were selected having body weight approximately 2 kg and divided into two main groups based on gender as male (n = 12) and female (n = 12). For milt collection, all males were treated with Ovaprim 0.5 mg/kg body weight (b.w.) and female fish were divided into three groups as A, B, and C with four (n = 4) fish in each group. Group A was injected with only normal saline (control group) while fish in group B and group C were treated with hMG at 0.5 mg/kg b.w. and Ovaprim 0.5 mg/kg b.w., respectively. Then, after 6 h of hormone injections until 48 h, spawned eggs, eggs' weight, fertilization rate, hatching rate, survival rate, fecundity, and deformed larvae were investigated. The results revealed that Ovaprim injection significantly (p < 0.05) modulate the reproductive parameters in group C while no breeding was induced in both control and hMG-treated groups. Hence, it could be concluded that Ovaprim has the potential to induce breeding in African catfish, while in the current study, hMG failed to induce breeding. However, trials at large scales are required to further explore the effect of different doses of both tested hormones by increasing the treated subjects particularly in Pakistani fish farms.

Assessment of ameliorative effect of Trigonella foenum-graecum against CuO-NPs induced toxicity in Oreochromis mossambicus.

The current study assessed the ameliorative effect of Trigonella foenum graceum extract against copper oxide nanoparticles (CuO-NPs) induced toxicity in Oreochromis mossambicus. For this purpose 100 healthy fish weighing 20±2.34g were randomly divided into five different groups in duplicates and designated as control (C) no treatment, positive control (G*) treated with 0.12mg/L of CuO-NPs, experimental co-treated groups G1, G2 and G3 were treated with Trigonella foenum-graecum extract @ 18, 26 and 52mg/L along with 0.12 mg/L of CuO-NPs, respectively. In this study significant (P<0.05) changes were observed in the antioxidant activity of enzymes and histological alterations in the liver and intestine of fish in G*, G1 and G2 groups while a good ameliorative response of Trigonella foenum-graecum was observed in G3. Dose dependent alterations in glutathione, lipid peroxides, catalase, and malondialdehyde as well as histological architecture of liver and intestine were observed in treated groups, where more alterations were observed in positive control and low dose treated groups of Trigonella foenum-graecum. Moreover, more ameliorative effect was observed in high dose of Trigonella foenum-graecum treated group (G3). This study is novel as no previous data is available on the amelioration of Trigonella foenum-graecum extract against CuO-NPs induced toxicity in fish.

In silico-based identification of phytochemicals as novel human phosphoglycerate mutase 1 (PGAM1) inhibitors for cancer therapy.

Targeting cancer-specific metabolic and mitochondrial remodeling has emerged as a novel and selective strategy for cancer therapy during recent years. Phosphoglycerate Mutase 1 (PGAM1) is an important glycolytic enzyme that catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate and plays a critical role in cancer progression by coordinating glycolysis and biosynthesis. PGAM1 has been reported to be over expressed in a variety of cancer types and its inhibition results in decreased tumor growth and metastasis. Recently, there has been a growing interest in identification and characterization of novel PGAM1 inhibitors for the treatment of cancer. In the current study, in silico tools were used to find out natural inhibitors of PGAM1. For docking studies, a database of 5006 phytochemicals were docked against PGAM1, using MOE software in order to identify the compounds which show better binding affinities than PGMI-004A. Out of 5006 compounds screened, eight compounds (1,3-cyclopentanedione, glyflavanone B, 6-demethoxytangeretin, gnaphaliin, lantalucratin A and -(-) morelensin, abyssinin II and monotesone-A) showed significant binding affinity with PGAMI active site. Further, the eight selected compounds were evaluated for different pharmacokinetics parameters using admetSAR, the obtained results demonstrated that none of these hit compounds violated Lipinski's drug rule of 5 and all the hit compounds possess favorable ADMET properties. This study has unveiled the potential of phytochemicals that could serve as probable lead candidates for the development of PGAM1 inhibitors as anti-cancer agents.

CYP17 gene polymorphic sequence variation is associated with hyperandrogenism in Kashmiri women with polycystic ovarian syndrome.

OBJECTIVE: Polycystic ovarian syndrome is a complex reproductive as well as endocrinological disorder characterized by anovulatory dysfunction, androgen excess and polycystic ovarian morphology. Hyperandrogenism is regarded as a cardinal feature of the disease. It is believed that the excess androgens are produced due to abnormality in steroid biosynthesis pathway wherein cytochrome P450, 17α-hydroxylase (CYP17) plays an imperative role. Therefore the objective of the present study was to analyze the T/C polymorphism in 5'UTR of CYP17 gene for its association with PCOS and hyperandrogenism in Kashmiri population. METHOD: A total of 700 subjects which included 394 PCOS patients and 306 healthy controls were recruited for the study. Their anthropometric, biochemical and hormonal parameters were analyzed. DNA was extracted followed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze the relationship of CYP17 gene polymorphism with PCOS and hyperandrogenism in PCOS. RESULTS AND CONCLUSION: The allelic as well as genotypic distribution did not show any significant difference between the cases and controls. However, PCOS patients with mutant genotype had significantly higher level of total testosterone and clinical features like FG score, alopecia than those of wild and heterozygous genotype, indicating association with hyperandrogenism in our Kashmiri population.

Investigation of oxidative stress enzymes and histological alterations in tilapia exposed to chlorpyrifos.

Chlorpyrifos (ChF) is an organophosphate pesticide that is widely used in agricultural fields and indoor for controlling pests. Aquatic ecosystems are the recipients of various pesticide residues due to leaching spray drift and agricultural runoff and pose toxicity for aquatic organisms. Therefore, the current study was designed to investigate the oxidative stress enzymes and histological alterations in the vital organs of tilapia due to ChF exposure. LC50 (24 h) was calculated as 52.78 µg/l by exposing tilapia with different acute concentrations of ChF. For assessment of sub-lethal toxicity of ChF, the fish were divided into four groups (ChF1, ChF2, ChF3, and control group). ChF1 group was treated with 1/15th of LC50, whereas ChF2 and ChF3 groups were treated with 1/10th and 1/5th of LC50, respectively for 14 days. After that, ChF induced changes in oxidative stress enzymes and histological alterations were evaluated. It was found that the level of glutathione S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) increased significantly in the liver of ChF-treated tilapia. Histological study of liver tissues showed an increased number of Kupffer cells, hydropic degeneration, necrosis, and hemorrhage. In the spleen of treated fish, increased melanomacrophage centers, necrosis, and congestion were detected. Disorganized muscle fibers, cardiac muscle fiber degeneration, and coagulative necrosis were observed in the heart of ChF-treated fish. It is concluded that sub-lethal concentrations of ChF can induce oxidative stress and histological alterations in the tissues of tilapia.

Histopathological changes and antioxidant responses in common carp (Cyprinus carpio) exposed to copper nanoparticles.

Despite the rapid increase of nanotechnology in a wide array of industrial sectors, the biosafety profile of nanomaterials remains undefined. The accelerated use of nanomaterials has increased the potential discharge of nanomaterials into the environment in different ways. The aquatic environment is mainly susceptible as it is likely to act as an ultimate sink for all contaminants. Therefore, this study assessed the toxicological impacts of waterborne engineered copper nanoparticles (Cu-NPs) on histology, lipid peroxidation (LPO), catalase (CAT), and glutathione (GSH) levels in the gills of common carp (Cyprinus carpio). Nanoparticles were characterized by XRD and SEM techniques. Before starting the sub-acute toxicity testing, 96 h LC50 of Cu-NPs for C. carpio was calculated as 4.44 mg/l. Then based on LC50, C. carpio of 40-45 g in weight were exposed to three sub-lethal doses of waterborne engineered Cu-NPs (0 or 0.5 or 1 or 1.5 mg/l) for a period of 14 days. The waterborne Cu-NPs have appeared to induce alterations in gill histology and oxidative stress parameters in a dose-dependent manner. The gill tissues showed degenerative secondary lamellae, necrotic lamella, fused lamella, necrosis of the primary and secondary lamella, edema, complete degeneration, epithelial lifting, degenerative epithelium, and hyperplasia in a dose-dependent manner. In the gill tissues, waterborne Cu-NPs caused a decreased level of CAT and elevated levels of LPO, and GSH in the fish exposed to the highest dose of 1.5 mg Cu-NPs/l of water. Our results indicate that the exposure to waterborne Cu-NPs was toxic to the aquatic organisms as shown by the oxidative stresses and histological alterations in C. carpio, a freshwater fish of good economic value.