CRISPR Cas9 mediated knockout of sex determination pathway genes in Aedes aegypti.

The vector role of Aedes aegypti for viral diseases including dengue and dengue hemorrhagic fever makes it imperative for its proper control. Despite various adopted control strategies, genetic control measures have been recently focused against this vector. CRISPR Cas9 system is a recent and most efficient gene editing tool to target the sex determination pathway genes in Ae. aegypti. In the present study, CRISPR Cas9 system was used to knockout Ae. aegypti doublesex (Aaedsx) and Ae. aegypti sexlethal (AaeSxl) genes in Ae. aegypti embryos. The injection mixes with Cas9 protein (333 ng ul-1) and gRNAs (each at 100 ng ul-1) were injected into eggs. Injected eggs were allowed to hatch at 26 ± 1°C, 60 ± 10% RH. The survival and mortality rate was recorded in knockout Aaedsx and AaeSxl. The results revealed that knockout produced low survival and high mortality. A significant percentage of eggs (38.33%) did not hatch as compared to control groups (P value 0.00). Highest larval mortality (11.66%) was found in the knockout of Aaedsx female isoform, whereas, the emergence of only male adults also showed that the knockout of Aaedsx (female isoform) does not produce male lethality. The survival (3.33%) of knockout for AaeSxl eggs to the normal adults suggested further study to investigate AaeSxl as an efficient upstream of Aaedsx to target for sex transformation in Ae. aegypti mosquitoes.

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.

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.

Transformation of libraries during Covid-19 pandemic: A systematic review.

Purpose: This study analyze academic library services during Covid-19 pandemic (2020 and 2021), as well as the challenges they face, emerging library roles, and the most effective communication tools. Method: A systematic review of the relevant literature was undertaken following PRISMA guidelines. The relevant literature was retrieved from four major scholarly databases (Scopus, Web of Science, Library, Information Science & Technology Abstracts (LISTA), and Library and Information Science Abstracts (LISA)). The relevant 23 studies were included fulfilling inclusion criteria. A quality assessment of the included studies was also performed. Findings: The findings revealed that Covid-19 pandemic is certainly effecting and transforming libraries, their services and management. The library services during Covid-19 pandemic, their fundamental challenges, emerging roles, and available preferable communications tools are the categories in this study to better understand the pandemic-transformation. Implications: The practical and policy implications are that libraries must establish infrastructure and improve accessibility in order to provide the best possible support to modern library users who access resources remotely in this rapidly evolving digital environment. Organizational policymakers and library directors should prepare emergency and disaster management plans. The libraries should ensure their presence on social media and make use of their library websites.

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.

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.

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.

Tuberculosis Preventive Therapy for Individuals Exposed to Drug-resistant Tuberculosis: Feasibility and Safety of a Community-based Delivery of Fluoroquinolone-containing Preventive Regimen.

BACKGROUND: Observational studies have demonstrated the effectiveness of a fluoroquinolone-based regimen to treat individuals presumed to be infected with drug-resistant tuberculosis (DR-TB). We sought to assess the feasibility of this approach in an urban setting in South Asia. METHODS: From February 2016 until March 2017, all household contacts of DR-TB patients enrolled at the Indus Hospital were screened for TB symptoms at home. Children aged 0-17 years, symptomatic adults, and those with an immunocompromising condition (human immunodeficiency virus, diabetes, or malnutrition) were evaluated for TB disease. Contacts diagnosed with TB disease were started on treatment. Contacts without TB disease aged <5 years, contacts aged between 5 and 17 years with either a positive tuberculin skin test or an immunocompromising condition, or contacts aged ≥18 years with an immunocompromising condition were offered 6 months of treatment with a fluoroquinolone. RESULTS: One hundred households with 800 contacts were enrolled: 353 (44.1%) individuals aged ≤17 years with a median age of 19 years (interquartile range, 10-32); 423 (52.9%) were males. In total, 737 (92.1%) individuals were screened, of which 8 were already on treatment for TB (1.1%); another 3 (0.4%) contacts were diagnosed with TB disease and started on treatment. Of 215 eligible for infection treatment, 172 (80.0%) contacts initiated and 121 (70.3%) completed treatment. No TB disease or significant adverse events were observed during 12 months of follow-up. CONCLUSIONS: Fluoroquinolone-based treatment for contacts with presumed DR-TB infection is feasible and well tolerated in a high TB burden setting.

Progress and prospects in the management of psoriasis and developments in phyto-therapeutic modalities.

The aim of this study is to review the efficacy of herbal and allopathic drugs used to manage and treat psoriasis. The review has been compiled using reference materials from major databases, Online Journals, Science Direct, Scopus, Open J Gate, Google Scholar and PubMed. Psoriasis is a common skin disease affecting 2-3% of the world's population. It is cosmetically debilitating and chronic disease, which occurs both in developing and developed countries. It can affect any part of the body, but the most common sites are the elbows, knees, and scalp. It is usually treated with synthetic medicine either given systematically or applied locally. The prescribed synthetic medicines used for the treatment of psoriasis are associated with severe side effects and complications, thus researchers around the world are trying to explore new, more effective, and safer drugs from natural resources. Medicinal plants are safe and efficacious, and most of the people all over the world rely on herbal medicine due to their easy availability, low cost, and efficacy for treating psoriasis. A number of medicinal plants having therapeutic potential with high efficacy are used in the treatment of psoriasis have been described. Moreover, studies should be conducted to isolate and investigate the mechanism of actions of phytochemicals responsible for anti-psoriasis potential.

Therapeutic potential of medicinal plants for the management of urinary tract infection: A systematic review.

Urinary tract infection (UTI) is one of the most severe public health problem affecting both sexes but females are more susceptible due to the differences in urogenital and reproductive anatomy, physiology and lifestyle. As in UTI, different parts of the urinary tract are affected and morbidity due to UTI is more common in women of all ages and older men. Due to multi-drug resistant strains and high recurrence rate, UTI has become a major socioeconomic burden. The current review article was aimed to describe the natural therapeutic strategies to manage and cure the UTI. For this purpose, different databases including Google Scholar, Cochrane database, and PubMed etc. were explored. Inclusion criteria were any research article investigating the current therapy of UTI. It was found that microbial infections including Escherichia coli, Enterococcus faecalis and Klebsiella species are the major causes of UTI with different signs and symptoms including painful urination or dysuria, hematuria, urinary urgency, burning micturition, frequent urination, nausea, and vomiting. Antibiotics like trimethoprim, sulfamethoxazole, quinolone etc. as the first choice of the drug are used worldwide. However, due to microbial resistance, several life-threatening side effects, repeated high doses, high cost and low efficacy of these antibiotics motivated the researchers to explore natural remedies for the treatment of UTI. Herbal medicines are effective to combat bacterial resistance with high efficacy, and easy availability with minimal or no side effects. For these reasons it has attained the attention of researchers wanting to explore the herbal treatment of UTI. Vaccinium macrocarpon, Tribulus terrestris, Trachyspermum copticum, Cinnamomum verum and Hybanthusenn easpermus are some common medicinal plants reported to have therapeutic potential for the management and cure of the UTI. Although herbal medicines have more potential over conventional medicine but more discoveries are required to explore the phytoconstituents and their mechanism of action responsible for the management and cure of UTI.

Neurotoxic effects of titanium dioxide nanoparticles on the brain of male sprague dawley rats.

Titanium dioxide nanoparticles have diverse applications in many fields and are used in cosmetics, sterilization, paints, tooth paste, food products, air cleaning, sunscreens and waste water treatment plants due to their unique properties. But on the other hand, the wide use of titanium dioxide nanoparticles raises concerns to the upcoming challenges of human health. This study assessed the neurotoxic effect of titanium dioxide nanoparticles by histology, cell viability, oxidative stress and acetylcholine esterase level. For this purpose, 28 days old, post weaning male Sprague Dawley rats (n=25) were procured from the animal house of the Government College University, Faisalabad. Rats were randomly divided into five groups with five rats in each group and designated as Control (C) without treatment, Placebo group (S) treated with 0.9% normal saline and three nanoparticles treated groups (Group 1 of 80 mg/kg, Group 2 of 120 mg/kg and Group 3 of 160 mg/kg body weight of rat). Nanoparticles were injected intraperitonealy on alternate days for 28 days. On 29th day, rats were sacrificed and brain was isolated from all groups. Accumulation of titanium in the brain was assessed by inductively coupled plasma mass spectrometry (ICP-MS) and its increase in concentration was observed in a dose dependent manner. Cell viability, acetylcholine esterase and glutathione activities were significantly (P<0.05) decreased in Group 2 and Group 3 treated groups as compared to control and placebo groups. Histological alterations were also reported in brain exposed to titanium dioxide nanoparticles treated groups. This study revealed that titanium dioxide nanoparticles are neurotoxic as expressed by histological alterations, reduced cell viability, reduced acetylcholine esterase activity and induced oxidative stress by reducing glutathione activity in male Sprague Dawley rats.

Eriocalyxin B induces apoptosis in human triple negative breast cancer cells via inhibiting STAT3 activation and mitochondrial dysfunction.

Eriocalyxin B (EriB), a potent ent-kaurene extracted from Isodon eriocalyx, has turned up as novel anti-cancer agent during recent years against a range of cancer types. TNBC (Triple negative breast cancer) is highly aggressive breast cancer, which is resistant towards current therapeutics due to absence of drug targets. Here, we have probed the molecular mechanism of EriB-induced apoptosis in TNBC (MDA-MB231) cells to check whether its anticancer activity is mediated by modulation of STAT3 and NF-Ï°B. EriB induced apoptosis in MDA-MB231 cells via inhibiting NF-Ï°Bp65, STAT3 phosphorylation, increasing Bax/Bcl-2 ratio, MMP dissipation, and activation of caspase-3. These results provide a rationale for further in vivo investigations on EriB, which might also prove to be a potential drug candidate for developing novel therapeutics against TNBC.

Reconnoitring the impact of different extraction techniques on ginger bioactive moieties extraction, antioxidant characterization and physicochemical properties for their therapeutic effect.

The core directive of current study was to compare the different extraction techniques for their extraction yield of ginger bioactive moieties. Purposely, ultrasonic assisted and supercritical fluid extraction techniques were adapted alongside conventional solvent extraction for comparison. The variables targeted for the extraction process in different modules were time (20, 30, 40 minutes), temperature (30, 40, 50oC), solvent to sample ratio (4:6, 6:4, 8:2), pressure (2000, 3000, 4000 psi) and amplitude (20, 30, 40%). All variables were found to be momentously (P>0.05) effecting the extraction rates. The antioxidant potential of bioactive moieties was evaluated through FRAP, DPPH and ABTS. The outcomes of the optimization process suggested that the total phenolic content and total flavonoids content extracted through 80% ethanol at 50oC for 40 minutes showed maximum antioxidant activity. However, ultrasound assisted extraction, by using 80% ethanol, at 50oC for 40 minutes and at ultrasonic amplitude of 40% exhibited best results. Moreover, supercritical fluid extraction at 50oC for 40 minutes at5000 psi pressure, showed maximum extraction potential. All the extracts gathered through conventional, ultrasound and supercritical techniques were further quantified through HPLC protocols. The statistical interpretation of the results from all the analytical findings revealed highest concentration of polyphenols in supercritical fluids extracts followed by ultrasound and conventional extracts. One best treatment on the basis of superior nutritional profile as depicted by HPLC quantification was selected for the formulation of ginger drink. Physicochemical analysis elucidated momentous upshot on color, pH and acidity with progressive storage period whereas TSS followed a non-significant trend. Moreover, storage interval and treatments significantly affected the antioxidant potential of drinks.

Malic enzyme 2 as a potential therapeutic drug target for cancer.

Reprogrammed metabolic profile is a biochemical fingerprint of cancerous cells, which represents one of the "hallmarks of cancer." The aberrant expression pattern of enzymatic machineries orchestrates metabolic activities into a platform that ultimately promotes cellular growth, survival, and proliferation. The NADP(+)-dependent mitochondrial malic enzyme 2 (ME2) has been widely appreciated due to its function as a provider of pyruvate and reducing power to the cell for biosynthesis of fatty acids and nucleotides along with maintenance of redox balance. Multiple lines of evidences have indicated that ME2 is a bonafide therapeutic target and novel biomarker which plays critical role during tumorigenesis. The objective of this review is to provide an update on the cancer-specific role of ME2 in order to explore its potential for therapeutic opportunities. Furthermore, we have discussed the potential of genetic and pharmacological inhibitors of ME2 in the light of previous research work for therapeutic advancements in cancer treatment. It is contemplated that additional investigations should focus on the use of ME2 inhibitors in combinational therapies as rational combinations of metabolic inhibitors and chemotherapy may have the ability to cure cancer. © 2018 IUBMB Life, 70(11):1076-1083, 2018.

Assessment of copper nanoparticles (Cu-NPs) and copper (II) oxide (CuO) induced hemato- and hepatotoxicity in Cyprinus carpio.

Recently, Cu-based nanoparticles have drawn considerable attention for their various fascinating roles in multiple biological systems. It is recognized that their frequent use can create compatibility challenges for the recipient systems. Nevertheless, it is unclear how various biological interactions affect the compatibility of Cu oxide II (CuO) and Cu oxide nanoparticles (Cu-NPs) for different organisms. Consequently, it has been difficult to perform structured risk assessments for their use in biological systems. Therefore, this study compared the effects of different doses of waterborne Cu-NPs and CuO on the blood and liver of selected groups of Cyprinus (C) carpio. These fish while housed in suitable water tanks were exposed to one of the following treatments for 14 d: control (no added Cu) or 0.5 or 1 or 1.5 mg Cu as Cu-NPs or CuO l-1 of water. We found significant changes in all assessed blood parameters of fish in response to increasing doses from 0 to 1.5 mg of Cu-NPs or CuO. Similarly, increased levels of lipid peroxide and reduced glutathione (GSH) were also observed in the livers of C. carpio in Cu-NPs or CuO treated groups. Enhanced levels of lipid peroxidation and GSH were also recorded in the Cu-NP treated groups compared with the CuO treated groups in a dose dependent manner. The lowest catalase activity was observed in the liver of C. carpio treated with the higer dose of Cu-NPs. Cu-NP or CuO exposure induced significant histological alterations in the liver of C. carpio including focal necrosis, cloudy swelling of hepatocytes, degenerative hepatocytes, vacuolization, pyknotic nuclei, damaged central vein, nuclear hypertrophy, dilated sinusoid, vacuolated degeneration, congestion, and complete degeneration in a dose dependent manner. Substantial alterations in blood and liver specimens were observed in the Cu-NP treated fish when compared with the CuO treated fish. It appeared that the Cu-NPs were more toxic than the CuO as shown by the hemato- and hepatotoxicity in C. carpio of this study.

Ameliorative effects of Moringa oleifera on copper nanoparticle induced toxicity in Cyprinus carpio assessed by histology and oxidative stress markers.

Nanoparticles (NPs) enter the environment mainly through waste water effluents, accidental spillage, and industrial runoffs. This is worrying because NPs can enter the human body owing to their large aspect-to-size ratio and reactive surfaces that facilitate their penetration through biological barriers and thus can induce oxidative stress in host cells. Therefore, there is a growing concern about the toxicity of NPs, which needs to be addressed. Thus, this study investigated the ameliorative effects of Moringa oleifera seed extract (MOSE) in Cyprinus carpio exposed to copper nanoparticles (Cu-NPs). For the in vivo assessment of the shielding effects of MOSE, 240 samples of C. carpio (40-45 g) were randomly allocated to 24 experimental tanks (10 fish/tank of 40 L) 24 h prior to the start of this experiment. The experimental fish were faced with the water-born exposure of a pre-determined dose of 1.5 mg Cu-NPs/l along with pre- and post-treatment with different doses (100 or 200 or 300 mg l-1) of MOSE for 28 days. The MOSE showed significant ameliorative effect on the antioxidant defense, in response to the elevated levels of Cu-NP-induced oxidative stress. It also played a protective role as indicated by the suppression of the histological alterations in the gills and liver of fish exposed to the Cu-NPs. It was concluded that the Cu-NP-induced toxicity in C. carpio was ameliorated by the use of MOSE in this study. Moreover, the post-Cu-NP treatment stage showed more protective effects of MOSE than the pre-Cu-NP treatment phase. Further studies are suggested to determine the optimum dose and delivery method of MOSE for similar or different NP exposed fish.