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Primary liver cancer is a heterogeneous disease. Liver cancer metabolism includes both the reprogramming of intracellular metabolism to enable cancer cells to proliferate inappropriately and adapt to the tumor microenvironment and fluctuations in regular tissue metabolism. Currently, metabolomics and metabolite profiling in liver cirrhosis, liver cancer, and hepatocellular carcinoma (HCC) have been in the spotlight in terms of cancer diagnosis, monitoring, and therapy. Metabolomics is the global analysis of small molecules, chemicals, and metabolites. Metabolomics technologies can provide critical information about the liver cancer state. Here, we review how liver cirrhosis, liver cancer, and HCC therapies interact with metabolism at the cellular and systemic levels. An overview of liver metabolomics is provided, with a focus on currently available technologies and how they have been used in clinical and translational research. We also list scalable methods, including chemometrics, followed by pathway processing in liver cancer. We conclude that important drivers of metabolomics science and scientific technologies are novel therapeutic tools and liver cancer biomarker analysis. [ABSTRACT FROM AUTHOR]

Intestinal microbiota-derived microbial metabolites characterize the metabolic pathways and build the phenotypic expression in alcoholic fatty liver disease (AFLD) and non-AFLD (NAFLD). Microbial metabolites play significant roles in host-microbiota crosstalk. In this review, short-chain fatty acids (SCFAs: acetate (C 2), propionate (C 3) and butyrate (C 4)) and bile acids (BA: primary BAs, deconjugation, and secondary BAs) signify the fatty liver inflammation and liver carcinogenesis in both AFLD and NAFLD. Clinical investigations on autoimmune, inflammation, and malignancy have demonstrated the immunoregulatory capacity of SCFAs and BAs generated from the gut microbiota, which are reliant on dietary components. Variations in signaling, metabolic, and epigenetic states are among the multiple regulatory processes of SCFAs and BAs that support both the beneficial and detrimental effects of bacterial metabolites. In this review, we discuss SCFAs and BAs signaling and their interplay with the gut microbiome in FLD and NFLD. This review aims to define the key metabolites that are altered in AFLD and NAFLD and their roles in pathogenesis. They represent potential biomarkers for metabolic disorders. Furthermore, the clinical therapeutic applications of SCFAs and BAs profiles and metabolisms are selectively highlighted. • The metabolic variations of short-chain fatty acids (SCFAs) were studied in liver diseases. • SCFAs influenced metabolic alterations in liver metabolisms. • SCFAs has inhibited metabolic activity in gut microbiome. • Bile acids induced changes an quantitate variability of metabolites and metabolic pathways. [ABSTRACT FROM AUTHOR]

In this study, Box-Behnken design (BBD) in response surface methodology (RSM) was employed to optimize As(V) removal from an aqueous solution onto synthesized crosslinked carboxymethylchitosan-epichlorohydrin/Fe3O4 nanao- composite. The factors like solution pH, adsorbent dose, contact time and temperature were optimized by the method which shows high correlation coefficient (R² = 0.9406), and a predictive quadratic polynomial model equation. The adequacy of the model and parameters were evaluated by analysis of variance (ANOVA) with their significant factors of Fischer's F-test (p < 0.05). Seven significant parameters with interaction effects in the experiment with p-value < 0.0001 was observed, having a maximum removal efficiency of As(V) is 95.1%. Optimal conditions of dosage, pH, temperature, initial ion concentration and contact time in the process were found to be 0.7 g, pH 6.5, 308K, 10 mg/L and 60 min respectively. Langmuir isotherm model fitted better than the Freundlich model having a maximum adsorption capacity of 28.99 mg/g, a high regression value of 0.9988, least chi-square value of 0.1781. The process was found to follow monolayer adsorption and pseudo-second-order kinetics. Thermodynamic parameters indicate the process is spontaneous, endothermic and physisorption in nature. Successful regeneration of the adsorbent implies its applicability to the removal of arsenic from real life wastewater. [ABSTRACT FROM AUTHOR]

In the present work iron particles was recovered by dry magnetic separation, from waste steel slag, doped with chitosan for adsorbent prepared, characterized and evaluated for the removal of As(V) from an aqueous solution. The adsorption of As(V) was optimized by using response surface methodology through Box-Behnken design model, which gave high correlation coefficient (R² = 0.9175), and a predictive model of quadratic polynomial equation. Analysis of variance and Fischer's F-test were used to govern the parameters which interrupt the adsorption of As(V).The adsorbent was characterized by FTIR, XRD and SEM. Optimal conditions, including adsorbent dosage, pH, temperature, initial ion concentration and contact time for the removal of As(V), were found to be 0.8 g, pH 4, 308 K, 10 mg L-1 and 3 h, respectively. Langmuir isotherm model fitted better compared to the Freundlich model having a maximum adsorption capacity of 11.76 mg g-1, a high regression coefficient value of 0.993 and least chi-square value of 0.1959. The process was found to follow monolayer adsorption and pseudo-second-order kinetics. Thermodynamic parameters such as S, H and G indicated the feasibility, spontaneous and endothermic nature of adsorption. Successful regeneration of the adsorbent implies its applicability to the removal of arsenic from real life wastewater. [ABSTRACT FROM AUTHOR]

[Display omitted] Adjuvant chemotherapy is highly recommended for liver cancer to enhance survival rates due to its tendency to recur frequently. Localized drug-eluting implants have gained traction as an alternative to overcome the limitations of systemic chemotherapy. This work describes the development of biodegradable 3D printed (3DP) bilayer films loaded with 5-fluorouracil (5FU) and cisplatin (Cis) with different infill percentages where the 5FU layers were 40%, 30%, and 30% and Cis layers were 10%, 15%, and 10% for films A, B, and C, respectively. The relevant characterization tests were performed, and the drug content of films was 0.68, 0.50, and 0.50 mg of 5FU and 0.39, 0.80, and 0.34 mg of Cis for films A, B, and C, respectively. Cis release was affected by the alterations to the film design, where films A, B, and C showed complete release at 12, 14, and 23 days, respectively. However, 5FU was released over 24 h for all films. The films were stable for up to two weeks after storage at 25 °C/65% relative humidity and four weeks at 4 °C where drug content, tensile strength, FTIR, and thermal analysis results demonstrated negligible alterations. The cytotoxicity of the films was assessed by MTS assays using HepG2 cell lines demonstrating up to 81% reduction in cell viability compared to blank films. Moreover, apoptosis was confirmed by Western Blots and the determination of mitochondrial cell potential, highlighting the potential of these films as a promising approach in adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac arrest in children is a fatal incident usually ending in death or very poor neurological results. Western countries that have reliable data have put in place, mechanisms to anticipate cardiac arrest due to common condition and also effective response for a cardiac arrest in vulnerable children. The prevalence and survival of paediatric cardiopulmonary arrest are not well-studied in a developing country like India. Moreover, data regarding the effectiveness of CardioPulmonary Resuscitation (CPR) and the survival of children after suffering cardiac arrest in the hospital is also scarce from developing countries. Data on the precipitating events, survival and predictors of adverse outcome of cardiac arrest in our patient population can potentially help us in planning for the delivery of better care to our patients. The differences in data from India and rest of the world are highlighted. Aim: To identify underlying aetiology, precipitating factors, the outcome in terms of survival, and the predictors of survival among hospitalised paediatric patients developing cardiac arrest. Materials and Methods: This prospective descriptive study was conducted from October 2012 to June 2014 in JIPMER, a tertiary care teaching institute in southern India. A total of 137 cases were included in the study. There clinical baseline, pre-arrest, arrest, post-arrest parameters were recorded. Final outcome of the patient as survival or death was also recorded. For the survivors Paediatric Cerebral Performance Category (PCPC) measure of cognitive function was recorded. The result obtained from the study was analysed using SPSS 20.0. Results: Total 137 patients included in the study after qualified the inclusion criteria and majority 77 (56.2%) patients were infants. Infections was major 103 (75.18%) underlying aetiology. 126 cases (92%) of the observed cardiac arrest occurred in Paediatric Intensive Care Unit (PICU). Return of Spontaneous Circulation (ROSC) was achieved in 82 children (59.8%) and 27 children (19.7%) survived to hospital discharge. A 77.8% of the survivors had normal to mild disability and one patient (<1%) had severe disability at discharge. Most common observed rhythm at the time of cardiac arrest was bradycardia100 (72.9%) cases. At the time of arrest, prolonged CPR, multiple doses of adrenaline, venous blood gas disturbances were predictors of poor outcome. In the post-arrest period, presence of hypotension, prolonged capillary refilling time, low SpO2, hypothermia and lab parameters like thrombocytopenia and liver dysfunction were associated with poor outcome. Conclusion: In paediatric CPR prevalence of survival is absolutely excellent. Independent association between many parameters and hospital mortality is established. Subsequent research should focus on whether each of these association establish as cause and effect in future. In paediatric cardiac arrest clinical epidemiologist determining the efficiency of present day interventions like therapeutic hypothermia is crucial to recognise these associations in their research methodology. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Typhimurium exploits the host's type I interferon (IFN-I) response to induce receptor-interacting protein (RIP) kinase-mediated necroptosis in macrophages. However, the events that drive necroptosis execution downstream of IFN-I and RIP signaling remain elusive. In this study, we demonstrate that S. Typhimurium infection causes IFN-I-mediated up-regulation of the mitochondrial phosphatase Pgam5 through RIP3. Pgam5 subsequently interacts with Nrf2, which sequesters Nrf2 in the cytosol, thereby repressing the transcription of Nrf2-dependent antioxidative genes. The impaired ability to respond to S. Typhimurium-induced oxidative stress results in reactive oxygen species-mediated mitochondrial damage, energy depletion, transient induction of autophagy, and autophagic degradation of p62. Reduced p62 levels impair interaction of p62 with Keap1, which further decreases Nrf2 function and antioxidative responses to S. Typhimurium infection, eventually leading to cell death. Collectively, we identify impaired Nrf2-dependent redox homeostasis as an important mechanism that promotes cell death downstream of IFN-I and RIP3 signaling in S. Typhimurium-infected macrophages. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is becoming more common and severe. Individuals with NAFLD have an altered composition of gut- microbial metabolites. We used metabolomics profiling to identify microbial metabolites that could indicate gut-liver metabolic severity. Noninvasive biomarkers are required for NAFLD, especially for patients at high risk of disease progression. We compared the stool metabolomes, untargeted metabolomics, and clinical data of 80 patients. Patients with nonalcoholic fatty liver (NAFL: n = 16), nonalcoholic steatohepatitis (NASH: n = 26), and cirrhosis (n = 19) and healthy control individuals (HC: n = 19) were enrolled. The identified metabolites in NAFLD were evaluated by multivariate statistical analysis and metabolic pathotypic expression. Gas chromatography–mass spectrometry (GC–MS) and liquid chromatography coupled to time-of-flight–mass spectrometry (LC–TOF-MS) were used to analyze metabolites. Untargeted metabolomics was used to identify and quantify 103 metabolites. Principal component analysis (PCA) was used to assess the metabolic discrimination of NAFL, NASH, and cirrhosis. Short-chain fatty acids (SCFA) levels were significantly lower in NAFLD patients, including those of acetate (p = 0.03), butyrate (p = 0.0008), and propionate. The stool cholic acid (p = 0.001) level was significantly increased in NAFLD patients. Palmitoylcarnitine and l -carnitine levels were significantly increased in NASH and cirrhosis patients. The phenotypic expression of these metabolites was linked to β-oxidation. We demonstrated a distinct metabolome profile in NAFLD patients with NAFL, NASH, and cirrhosis. We also discovered that the expression of certain metabolites and metabolic pathways was linked to NAFLD. • A workflow was developed for NAFLD through untargeted metabolomics analysis. • The effect of non-alcohol consumption on the metabolome was quantified and investigated. • Metabolic injuries of NAFL, NASH, and cirrhosis were analyzed. • Fatty acids, bile acids, amino acids, and organic molecules could significantly alter human stool samples. • Short-chain fatty acids, linolenic acid, and indole metabolites were identified and recommended for clinical therapeutics. [ABSTRACT FROM AUTHOR]

We comprised metabolites of gut microbiota (GM; endogenous species) and dietary plant-derived natural flavonoids (DPDNFs; exogenous species) were known as potent effectors against non-alcoholic fatty liver disease (NAFLD) via network pharmacology (NP). The crucial targets against NAFLD were identified via GM and DPDNFs. The protein interaction (PPI), bubble chart and networks of GM or natural products-metabolites-targets-key signalling (GNMTK) pathway were described via R Package. Furthermore, the molecular docking test (MDT) to verify the affinity was performed between metabolite(s) and target(s) on a key signalling pathway. On the networks of GNMTK, Enterococcus sp. 45, Escherichia sp.12, Escherichia sp.33 and Bacterium MRG-PMF-1 as key microbiota; flavonoid-rich products as key natural resources; luteolin and myricetin as key metabolites (or dietary flavonoids); AKT Serine/Threonine Kinase 1 (AKT1), CF Transmembrane conductance Regulator (CFTR) and PhosphoInositide-3-Kinase, Regulatory subunit 1 (PIK3R1) as key targets are promising components to treat NAFLD, by suppressing cyclic Adenosine MonoPhosphate (cAMP) signalling pathway. This study shows that components (microbiota, metabolites, targets and a key signalling pathway) and DPDNFs can exert combinatorial pharmacological effects against NAFLD. Overall, the integrated pharmacological approach sheds light on the relationships between GM and DPDNFs. [ABSTRACT FROM AUTHOR]

During intracellular infections, autophagy significantly contributes to the elimination of pathogens, regulation of pro-inflammatory signaling, secretion of immune mediators and in coordinating the adaptive immune system. Intracellular pathogens such as S. Typhimurium have evolved mechanisms to circumvent autophagy. However, the regulatory mechanisms targeted by S. Typhimurium to modulate autophagy have not been fully resolved. Here we report that cytosolic energy loss during S. Typhimurium infection triggers transient activation of AMPK, an important checkpoint of mTOR activity and autophagy. The activation of AMPK is regulated by LKB1 in a cytosolic complex containing Sirt1 and LKB1, where Sirt1 is required for deacetylation and subsequent activation of LKB1. S. Typhimurium infection targets Sirt1, LKB1 and AMPK to lysosomes for rapid degradation resulting in the disruption of the AMPK-mediated regulation of mTOR and autophagy. The degradation of cytosolic Sirt1/LKB1/AMPK complex was not observed with two mutant strains of S. Typhimurium, ΔssrB and ΔssaV, both compromising the pathogenicity island 2 (SPI2). The results highlight virulence factor-dependent degradation of host cell proteins as a previously unrecognized strategy of S. Typhimurium to evade autophagy. [ABSTRACT FROM AUTHOR]

The present study investigates the hepatoprotective and antioxidant activity of alpha lipoic acid (ALA) on carbamazepine (CBZ) administered rats. 30 animals were divided into 5 groups. Animals in group 1 received drinking water orally and served as control, group 2 received CBZ 50 mg/Kg dissolved in water daily by oral gavage, group 3, 4 and 5 received (50, 100 and 200 mg/Kg) of ALA in 0.2% carboxy methyl cellulose respectively 1 hr prior to administration of 50 mg/Kg CBZ for a duration of 45 days. The levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase, bilirubin, albumin and total protein were estimated to determine the hepatoprotective activity. The levels of superoxide dismutase (SOD), glutathione (GSH), catalase and lipid peroxidation levels were estimated to determine the antioxidant activity. Histopathological examination was also done. CBZ increased the level of SGOT, GSH, catalase and increased lipid peroxidation. Administration of ALA reversed the CBZ induced hepatotoxicity. Histopathological examination revealed preservation of liver integrity in ALA administered rats compared to CBZ alone treated rats. The hepatoprotective effect of ALA was due to its antioxidant activity by scavenging free radicals. [ABSTRACT FROM AUTHOR]

Objectives: The present study evaluates the hepatoprotective activity of N-acetyl cysteine (NAC) against carbamazepine (CBZ)-induced hepatotoxicity. Materials and Methods: Rats were treated with CBZ (50 mg/kg p.o.) and CBZ supplemented with NAC 50, 100 and 200 mg/kg for 45 days, after which blood samples were collected and subjected to liver function tests. Animals were killed, liver was separated, weighed and the levels of antioxidants and liver enzymes were estimated. In addition, histopathological investigation was also performed. Results: Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate (SGOT) transaminase, alkaline phosphatase (ALP), bilirubin, lipid peroxidation, absolute and relative liver weights were significantly (P < 0.05) elevated, whereas serum levels of albumin, total protein and body weight were decreased in the CBZ-treated animals. CBZ also produced vacuolar degeneration, centrilobular congestion and hepatic necrosis as evidenced from histopathological report. NAC significantly reduced the levels of serum transaminase, ALP, bilirubin and liver weight and increased the levels of total protein, albumin and body weight. Conclusion: It was observed that NAC increased the glutathione (GSH) content, reduced lipid peroxidation and reversed the CBZ-induced histopathological abnormalities. CBZ-induced hepatotoxicity may be due its toxic epoxide metabolite-induced oxidative stress. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT), an endocrine disruptor is used globally in agribusiness and industries as biocides, heat stabilizers, and in chemical catalysis. It is known for its deleterious effects on bone by negatively impacting the functions of osteoblasts, osteoclasts and mesenchymal stem cells. However, the impact of TBT on the metabolomics profile in bone is not yet studied. Here, we demonstrate alterations in chemical metabolomics profiles measured by solid state 1H nuclear magnetic resonance (1H NMR) spectroscopy in zebrafish bone following tributyltin (TBT) treatment. TBT of 0, 100, 200, 300, 400 and 500 μg/L were exposed to zebrafish. From this, zebrafish bone has subjected for further metabolomics profiling. Samples were measured via one-dimensional (1D) solvent -suppressed and T 2 - filtered methods with in vivo zebrafish metabolites. A dose dependent alteration in the metabolomics profile was observed and results indicated a disturbed aminoacid metabolism, TCA cycle, and glycolysis. We found a significant alteration in the levels of glutamate, glutamine, glutathione, trimethylamine N-oxide (TMAO), and other metabolites. This investigation hints us the deleterious effects of TBT on zebrafish bone enabling a comprehensive understanding of metabolomics profile and is expected to play a crucial role in understanding the deleterious effects of various endocrine disruptor on bone. [Display omitted] • The metabolic changes of tributyltin (TBT) on zebrafish were studied using high-throughput screening. • TBT influenced metabolic alterations in bone metabolisms. • TBT has inhibited metabolic activity of energy, phospholipids, and neuroprotective pathways. • TBT induced changes and quantitates the variability of metabolites and metabolic pathways. [ABSTRACT FROM AUTHOR]

[Display omitted] • Metabolites and the gut microbiome have an association with Fatty liver disease. • Diagnosis of human diseases by surgery and biomarkers or metabolites-based methods. • Obesity metabolites and gut microenvironmental changes metabolomics profile. • Microbiome- metabolome study used for risk assessment of obesity and liver cancers. Fatty liver disease (FLD) is one of the largest burdens to human health worldwide and is associated with gut microbiome and metabolite stability. Engineered liver tissues have shown promise in restoring liver functions in non-alcoholic FLD (NAFLD), hepatitis and cirrhosis. Fatty liver, largely noted in obesity and hepatic cancer, is highly fatal and has led to a global increase in death rates. It is associated with complex metabolic reprogramming too. A standard approach to therapy in the newly diagnosed setting includes surgery or identification of biomarkers/ metabolites for therapeutic purposes, which ultimately focus on improvement of liver health in patients. As such there are no standard procedures for patient care, but depending on the severity, systemic therapy with either genomic, proteomic or metabolomic profiling form potential options. Better comparisons and study of underlying mechanisms in gut microbiome-based metabolic functions in obesity are urgently required. Today, an emerging field, focusing on metabolomic approaches and metabolic phenotyping, involved in high-throughput identification of metabolome in obesity and gut disorders, is involved in biomarker and metabolite identification. There are supporting technologies and approaches in NAFLD that throw light on the metabolites and gut microbiome, and also on the understanding of the risk factors of obesity along with liver cancer metabolic reaction networks. We discuss the current state of NAFLD metabolites, gut micro-environmental changes, and the further challenges in digital metabolomics profiling. Innovative clinical trial designs, with biomarker-enrichment strategies that are required to improve the outcome of NAFLD in patients are also discussed. [ABSTRACT FROM AUTHOR]

Regulation of cellular metabolism is now recognized as a crucial mechanism for the activation of innate and adaptive immune cells upon diverse extracellular stimuli. Macrophages, for instance, increase glycolysis upon stimulation with pathogen-associated molecular patterns (PAMPs). Conceivably, pathogens also counteract these metabolic changes for their own survival in the host. Despite this dynamic interplay in host-pathogen interactions, the role of immunometabolism in the context of intracellular bacterial infections is still unclear. Here, employing unbiased metabolomic and transcriptomic approaches, we investigated the role of metabolic adaptations of macrophages upon Salmonella enterica serovar Typhimurium (S. Typhimurium) infections. Importantly, our results suggest that S. Typhimurium abrogates glycolysis and its modulators such as insulin-signaling to impair macrophage defense. Mechanistically, glycolysis facilitates glycolytic enzyme aldolase A mediated v-ATPase assembly and the acidification of phagosomes which is critical for lysosomal degradation. Thus, impairment in the glycolytic machinery eventually leads to decreased bacterial clearance and antigen presentation in murine macrophages (BMDM). Collectively, our results highlight a vital molecular link between metabolic adaptation and phagosome maturation in macrophages, which is targeted by S. Typhimurium to evade cell-autonomous defense. Author summary: Macrophages undergo metabolic adaptations when they respond to invading pathogens. On the other hand, pathogens are also known to disrupt metabolic pathways to evade immune defense. In this study, we have employed metabolomics and transcriptomics to unravel that S. Typhimurium abrogates glycolysis and the modulators of glycolysis such as insulin-signaling. Downregulation of glycolysis leads to reduced acidification of phagosomes resulting in impaired bacterial clearance and antigen presentation. Furthermore, we provide evidence that induction of glycolysis facilitates v-ATPase assembly and the acidification of phagosomes by mobilizing aldolase to the v-ATPase complex. Our results highlight a previously unknown molecular link between metabolism and phagolysosome, which is targeted by S. Typhimurium to evade cell-autonomous defense. [ABSTRACT FROM AUTHOR]

Persea americana fruit (PAF) is a favorable nutraceutical resource that comprises diverse unsaturated fatty acids (UFAs). UFAs are significant dietary supplementation, as they relieve metabolic disorders, including obesity (OB). In another aspect, this study was focused on the anti‐OB efficacy of the non‐fatty acids (NFAs) in PAF through network pharmacology (NP). Natural product activity & species source (NPASS), SwissADME, similarity ensemble approach (SEA), Swiss target prediction (STP), DisGeNET, and online Mendelian inheritance in man (OMIM) were utilized to gather significant molecules and its targets. The crucial targets were adopted to construct certain networks: protein–protein interaction (PPI), PAF‐signaling pathways‐targets‐compounds (PSTC) networks, a bubble chart, molecular docking assay (MDA), and density function theory (DFT). Finally, the toxicities of the key compounds were validated by ADMETlab 2.0 platform. All 41 compounds in PAF conformed to Lipinski's rule, and the key 31 targets were identified between OB and PAF. On the bubble chart, PPAR signaling pathway had the highest rich factor, suggesting that the pathway might be an agonism for anti‐OB. Conversely, estrogen signaling pathway had the lowest rich factor, indicating that the mechanism might be antagonism against OB. Likewise, the PSTC network represented that AKT1 had the greatest degree value. The MDA results showed that AKT1‐gamma‐tocopherol, PPARA‐fucosterol, PPARD‐stigmasterol, (PPARG)‐fucosterol, (NR1H3)‐campesterol, and ILK‐alpha‐tocopherol formed the most stable conformers. The DFT represented that the five molecules might be promising agents via multicomponent targeting. Overall, this study suggests that the NFAs in PAF might play important roles against OB. [ABSTRACT FROM AUTHOR]

The present investigation aimed to determine the fungal toxicity of Isaria tenuipes (My-It) against the dengue mosquito vector Aedes aegypti L. and its non-target impact against the aquatic predator Toxorhynchites splendens. Lethal concentrations (LC50 and LC90) of My-It were observed in 2.27 and 2.93 log ppm dosages, respectively. The sub-lethal dosage (My-It-1 x 104 conidia/mL) displayed a significant oviposition deterrence index and also blocked the fecundity rate of dengue mosquitos in a dose-dependent manner. The level of major detoxifying enzymes, such as carboxylesterase (α-and β-) and SOD, significantly declined in both third and fourth instar larvae at the maximum dosage of My-It 1 x 105 conidia/mL. However, the level of glutathione S-transferase (GST) and cytochrome P-450 (CYP450) declined steadily when the sub-lethal dosage was increased and attained maximum reduction in the enzyme level at the dosage of My-It (1 x 105 conidia/mL). Correspondingly, the gut-histology and photomicrography results made evident that My-It (1 x 105 conidia/mL) heavily damaged the internal gut cells and external physiology of the dengue larvae compared to the control. Moreover, the non-target toxicity against the beneficial predator revealed that My-It at the maximum dosage (1 x 1020 conidia/mL) was found to be less toxic with <45% larval toxicity against Tx. splendens. Thus, the present toxicological research on Isaria tenuipes showed that it is target-specific and a potential agent for managing medically threatening arthropods. [ABSTRACT FROM AUTHOR]

The dynamic interplay between metabolism and immune responses in health and disease, by which different immune cells impact on metabolic processes, are being increasingly appreciated. However, the potential of master regulators of metabolism to control innate immunity are less understood. Here, we studied the cross-talk between leptin signaling and macrophage function in the context of bacterial infections. We found that upon infection with Gramnegative pathogens, such as Salmonella Typhimurium, leptin receptor (Lepr) expression increased in both mouse and human macrophages. Unexpectedly, both genetic Lepr ablation in macrophages and global pharmacologic leptin antagonization augmented lysosomal functions, reduced S. Typhimurium burden, and diminished inflammation in vitro and in vivo. Mechanistically, we show that leptin induction activates the mTORC2/Akt pathway and subsequently down-regulates Phlpp1 phosphatase, allowing for phosphorylated Akt to impair lysosomal-mediated pathogen clearance. These data highlight a link between leptin signaling, the mTORC2/ Phlpp1/Akt axis, and lysosomal activity in macrophages and have important therapeutic implications for modulating innate immunity to combat Gram-negative bacterial infections. [ABSTRACT FROM AUTHOR]

In this study, doxorubicin (DOX), silver nanoparticles (AgNPs), and DOX-AgNPs were used to screen metabolome activity in breast cancer (BC) cells. DOX and AgNPs may open an avenue for clinical application and BC metabolic inhibitors; however, their metabolic microenvironmental pathways are not well understood. To evaluate metabolic variations in DOX and AgNPs treated BC cells, proton nuclear magnetic resonance (1H NMR) spectra were coupled with univariate and multivariate statistical methods. The 100 µg/mL of DOX, AgNPs, and DOX-AgNPs-treated BC cells were significantly different from untreated BC cells when multivariate pattern recognition of 1H NMR spectrum data was used. The results show that DOX, AgNPs, and DOX-AgNPs reduced energy, amino acids, neurological, and oxidative stress metabolism. An adenosine monophosphate (AMP), an adenosine diphosphate (ADP), an adenosine triphosphate (ATP), glutathione (GSH), glutamine, glutamate, trimethylamine, and xanthine were all significantly affected. As a results, we propose that DOX, AgNPs, and DOX-AgNPs exposure affected an important metabolic pathway, like pyrimidine metabolism, sucrose metabolism, and glutathione metabolism in BC cells. Data will be made available on request. [Display omitted] • Metabolites profiling of doxorubicin (DOX) and silver nanoparticles (AgNPs) on breast cancer were studied using metabolomics. • DOX and AgNPs altered metabolic alterations in cancer metabolisms. • DOX and AgNPs has inhibited metabolic movement of energy, amino acids, phospholipids, and neuroprotective pathways. • DOX and AgNPs induced changes an quantitate metabolic discrimination and metabolic pathways. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is a serious public health issue globally, currently, the treatment of NAFLD lies still in the labyrinth. In the inchoate stage, the combinatorial application of food regimen and favorable gut microbiota (GM) are considered as an alternative therapeutic. Accordingly, we integrated secondary metabolites (SMs) from GM and Avena sativa (AS) known as potent dietary grain to identify the combinatorial efficacy through network pharmacology. Methods: We browsed the SMs of AS via Natural Product Activity & Species Source (NPASS) database and SMs of GM were retrieved by gutMGene database. Then, specific intersecting targets were identified from targets related to SMs of AS and GM. The final targets were selected on NAFLD-related targets, which was considered as crucial targets. The protein–protein interaction (PPI) networks and bubble chart analysis to identify a hub target and a key signaling pathway were conducted, respectively. In parallel, we analyzed the relationship of GM or AS─a key signaling pathway─targets─SMs (GASTM) by merging the five components via RPackage. We identified key SMs on a key signaling pathway via molecular docking assay (MDA). Finally, the identified key SMs were verified the physicochemical properties and toxicity in silico platform. Results: The final 16 targets were regarded as critical proteins against NAFLD, and Vascular Endothelial Growth Factor A (VEGFA) was a key target in PPI network analysis. The PI3K-Akt signaling pathway was the uppermost mechanism associated with VEGFA as an antagonistic mode. GASTM networks represented 122 nodes (60 GM, AS, PI3K-Akt signaling pathway, 4 targets, and 56 SMs) and 154 edges. The VEGFA-myricetin, or quercetin, GSK3B-myricetin, IL2-diosgenin complexes formed the most stable conformation, the three ligands were derived from GM. Conversely, NR4A1-vestitol formed stable conformation with the highest affinity, and the vestitol was obtained from AS. The given four SMs were no hurdles to develop into drugs devoid of its toxicity. Conclusion: In conclusion, we show that combinatorial application of AS and GM might be exerted to the potent synergistic effects against NAFLD, dampening PI3K-Akt signaling pathway. This work provides the importance of dietary strategy and beneficial GM on NAFLD, a data mining basis for further explicating the SMs and pharmacological mechanisms of combinatorial application (AS and GM) against NAFLD. [ABSTRACT FROM AUTHOR]

Mosquitoes are the potential vectors of several viral diseases such as filariasis, malaria, dengue, yellow fever, Zika fever and encephalitis in humans as well as other species. Dengue, the most common mosquito-borne disease in humans caused by the dengue virus is transmitted by the vector Ae. aegypti. Fever, chills, nausea and neurological disorders are the frequent symptoms of Zika and dengue. Thanks to various anthropogenic activities such as deforestation, industrialized farming and poor drainage facilities there has been a significant rise in mosquitoes and vector-borne diseases. Control measures such as the destruction of mosquito breeding places, a reduction in global warming, as well as the use of natural and chemical repellents, mainly DEET, picaridin, temephos and IR-3535 have proven to be effective in many instances. Although potent, these chemicals cause swelling, rashes, and eye irritation in adults and children, and are also toxic to the skin and nervous system. Due to their shorter protection period and harmful nature towards non-target organisms, the use of chemical repellents is greatly reduced, and more research and development is taking place in the field of plant-derived repellents, which are found to be selective, biodegradable and harmless to non-target species. Many tribal and rural communities across the world have been using plant-based extracts since ancient times for various traditional and medical purposes, and to ward off mosquitoes and various other insects. In this regard, new species of plants are being identified through ethnobotanical surveys and tested for their repellency against Ae. aegypti. This review aims to provide insight into many such plant extracts, essential oils and their metabolites, which have been tested for their mosquitocidal activity against different life cycle forms of Ae. Aegypti, as well as for their efficacy in controlling mosquitoes. [ABSTRACT FROM AUTHOR]

The metabolites of gut microbiota show favorable therapeutic effects on nonalcoholic fatty liver disease (NAFLD), but the active metabolites and mechanisms against NAFLD have not been documented. The aim of the study was to investigate the active metabolites and mechanisms of gut microbiota against NAFLD by network pharmacology. We obtained a total of 208 metabolites from the gutMgene database and retrieved 1256 targets from similarity ensemble approach (SEA) and 947 targets from the SwissTargetPrediction (STP) database. In the SEA and STP databases, we identified 668 overlapping targets and obtained 237 targets for NAFLD. Thirty-eight targets were identified out of those 237 and 223 targets retrieved from the gutMgene database, and were considered the final NAFLD targets of metabolites from the microbiome. The results of molecular docking tests suggest that, of the 38 targets, mitogen-activated protein kinase 8-compound K and glycogen synthase kinase-3 beta-myricetin complexes might inhibit the Wnt signaling pathway. The microbiota-signaling pathways-targets-metabolites network analysis reveals that Firmicutes, Fusobacteria, the Toll-like receptor signaling pathway, mitogen-activated protein kinase 1, and phenylacetylglutamine are notable components of NAFLD and therefore to understanding its processes and possible therapeutic approaches. The key components and potential mechanisms of metabolites from gut microbiota against NAFLD were explored utilizing network pharmacology analyses. This study provides scientific evidence to support the therapeutic efficacy of metabolites for NAFLD and suggests holistic insights on which to base further research. [ABSTRACT FROM AUTHOR]

In-vitro chemical characterization and mosquitocidal screening of essential oil derived from Mikania scandens (L.) Willd. (Asteraceae) (CVO-MS) against the malarial vector Anopheles gambiae was investigated. GC-MS analysis evidenced a total of 12 bio-active compounds, and maximum at α-bisabolol (39.34%) followed by stigmasterol (13.45%) respectively. The larvicidal activity of CVO-MS against the malarial vector An. gambiae evidenced that the mortality rate was prominent at the maximum dosage of 1000 ppm. The Median Lethal Concentration (LC50) of CVO-MS was established at 488±2.45 ppm, respectively. Enzyme inhibition assay showed that the CVO-MS delivers a significant upsurge in the level of CYP450, GST, and a decline in the level of α-β carboxylesterase activity in both the third and fourth instar (p ≤ 0.0001). The gut-histological examination of CVO-MS showed that there is severe damage in the mid-gut tissues, especially epithelial layer (EL), gut-lumen (GL), and peritrophic membrane (pM). The non-target screening against the mosquito predators (A. bouvieri, D. indicus, and third instar larvae of Tx. splendens) suggests that CVO-MS showed less toxicity as compared to Pestanal® (1 ppm) respectively. The present study has paved a new insight in understanding the bioactivity of CVO-MS as a potential larvicidal agent of malarial vector and non-toxic against mosquito predators. [ABSTRACT FROM AUTHOR]

Liver diseases are responsible for global mortality and morbidity and are a significant cause of death worldwide. Consequently, the advancement of new liver disease targets is of great interest. Non-coding RNA (ncRNA), such as microRNA (miRNA) and long ncRNA (lncRNA), has been proven to play a significant role in the pathogenesis of virtually all acute and chronic liver disorders. Recent studies demonstrated the medical applications of miRNA in various phases of hepatic pathology. PPARs play a major role in regulating many signaling pathways involved in various metabolic disorders. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, encompassing a spectrum spanning from mild steatosis to severe non-alcoholic steatohepatitis (NASH). PPARs were found to be one of the major regulators in the progression of NAFLD. There is no recognized treatment for NAFLD, even though numerous clinical trials are now underway. NAFLD is a major risk factor for developing hepatocellular carcinoma (HCC), and its frequency increases as obesity and diabetes become more prevalent. Reprogramming anti-diabetic and anti-obesity drugs is an effective therapy option for NAFLD and NASH. Several studies have also focused on the role of ncRNAs in the pathophysiology of NAFLD. The regulatory effects of these ncRNAs make them a primary target for treatments and as early biomarkers. In this study, the main focus will be to understand the regulation of PPARs through ncRNAs and their role in NAFLD. [ABSTRACT FROM AUTHOR]

The metabolites produced by the gut microbiota have been reported as crucial agents against obesity; however, their key targets have not been revealed completely in complex microbiome systems. Hence, the aim of this study was to decipher promising prebiotics, probiotics, postbiotics, and more importantly, key target(s) via a network pharmacology approach. First, we retrieved the metabolites related to gut microbes from the gutMGene database. Then, we performed a meta-analysis to identify metabolite-related targets via the similarity ensemble approach (SEA) and SwissTargetPrediction (STP), and obesity-related targets were identified by DisGeNET and OMIM databases. After selecting the overlapping targets, we adopted topological analysis to identify core targets against obesity. Furthermore, we employed the integrated networks to microbiota–substrate–metabolite–target (MSMT) via R Package. Finally, we performed a molecular docking test (MDT) to verify the binding affinity between metabolite(s) and target(s) with the Autodock 1.5.6 tool. Based on holistic viewpoints, we performed a filtering step to discover the core targets through topological analysis. Then, we implemented protein–protein interaction (PPI) networks with 342 overlapping target, another subnetwork was constructed with the top 30% degree centrality (DC), and the final core networks were obtained after screening the top 30% betweenness centrality (BC). The final core targets were IL6, AKT1, and ALB. We showed that the three core targets interacted with three other components via the MSMT network in alleviating obesity, i.e., four microbiota, two substrates, and six metabolites. The MDT confirmed that equol (postbiotics) converted from isoflavone (prebiotics) via Lactobacillus paracasei JS1 (probiotics) can bind the most stably on IL6 (target) compared with the other four metabolites (3-indolepropionic acid, trimethylamine oxide, butyrate, and acetate). In this study, we demonstrated that the promising substate (prebiotics), microbe (probiotics), metabolite (postbiotics), and target are suitable for obsesity treatment, providing a microbiome basis for further research. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) is a serious complication of cirrhosis that causes neuropsychiatric problems, such as cognitive dysfunction and movement disorders. The link between the microbiota and the host plays a key role in the pathogenesis of HE. The link between the gut microbiome and disease can be positively utilized not only in the diagnosis area of HE but also in the treatment area. Probiotics and prebiotics aim to resolve gut dysbiosis and increase beneficial microbial taxa, while fecal microbiota transplantation aims to address gut dysbiosis through transplantation (FMT) of the gut microbiome from healthy donors. Antibiotics, such as rifaximin, aim to improve cognitive function and hyperammonemia by targeting harmful taxa. Current treatment regimens for HE have achieved some success in treatment by targeting the gut microbiota, however, are still accompanied by limitations and problems. A focused approach should be placed on the establishment of personalized trial designs and therapies for the improvement of future care. This narrative review identifies factors negatively influencing the gut–hepatic–brain axis leading to HE in cirrhosis and explores their relationship with the gut microbiome. We also focused on the evaluation of reported clinical studies on the management and improvement of HE patients with a particular focus on microbiome-targeted therapy. [ABSTRACT FROM AUTHOR]

Alcohol consumption is a global healthcare problem. Chronic alcohol consumption generates a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, fibrosis, and cirrhosis. Alcoholic liver diseases (ALD) refer to liver damage and metabolomic changes caused by excessive alcohol intake. ALD present several clinical stages of severity found in liver metabolisms. With increased alcohol consumption, the gut microbiome promotes a leaky gut, metabolic dysfunction, oxidative stress, liver inflammation, and hepatocellular injury. Much attention has focused on ALD, such as alcoholic fatty liver (AFL), alcoholic steatohepatitis (ASH), alcoholic cirrhosis (AC), hepatocellular carcinoma (HCC), a partnership that reflects the metabolomic significance. Here, we report on the global function of inflammation, inhibition, oxidative stress, and reactive oxygen species (ROS) mechanisms in the liver biology framework. In this tutorial review, we hypothetically revisit therapeutic gut microbiota-derived alcoholic oxidative stress, liver inflammation, inflammatory cytokines, and metabolic regulation. We summarize the perspective of microbial therapy of genes, gut microbes, and metabolic role in ALD. The end stage is liver transplantation or death. This review may inspire a summary of the gut microbial genes, critical inflammatory molecules, oxidative stress, and metabolic routes, which will offer future promising therapeutic compounds in ALD. [ABSTRACT FROM AUTHOR]

[Display omitted] • High-resolution metabolomics detected metabolic activity in Mangifera indica L. with different environments. • Adverse outcomes occur as combination of 1H-NMR spectral data, multivariate data analysis, and profiling analysis. • Metabolic pathway perturbations related to cellular dysfunctions can found. • Interdisciplinary data science in Mangifera indica L. can address challenges of metabolites analysis. We examine the relationship between wetland (WL) and dryland (DL) Mangifera indica L with dietary-induced metabolic homeostasis. The typical Indian mango fruit Mangifera indica L has shown promise in the prevention of diarrhea and its complications. However, there is little information available regarding the characterization of organic compounds, metabolites, small molecules, and phytochemicals derived from Mangifera indica L. (Mango). In this study, we performed a global target profiling investigation of phytochemicals and inhibitors in Mangifera indica L.using proton nuclear magnetic resonance (1H NMR) signals. The glutathione (GSH), trimethylamine -N- oxcide (TMAO), and trimethylamine (TMO) are associated with disruptions of oxidative stress metabolisms. Metabolic differences of WL and DL mango were investigated with network analysis for revealing their metabolic discriminations. During plant life, fertilization, and biotic and abiotic stress reflected peculiar metabolomic profiles. The methodology is highly efficient, complex deconvolution, spectral baseline fitting that has transported to pattern recognition analysis. Fifty metabolites were identified and characterized which includes xanthones, phenolic acids, fatty acids, flavonoids, and amino acids. The current study is the first report of metabolites reglation by mango fruits. In conclusion, from Indian traditional mango fruits, we provide a perspective of metabolomic impacts and associated metabolic pathways with high-throughput analytical analysis. [ABSTRACT FROM AUTHOR]

The present research investigated the chemical characterization and insecticidal activity of n-Hexane extracts of Epaltes divaricata (NH-EDx) along with their chief derivatives n-Hexadecanoic acid (n-HDa) and n-Octadecanoic acid (n-ODa) against the dengue vector Aedes aegypti and lepidopteran pest Spodoptera litura. Chemical screening of NH-EDx through GC–MS analysis delivered nine major derivatives, and the maximum peak area percentage was observed in n-Hexadecanoic acid (14.63%) followed by n-Octadecadienoic acid (6.73%). The larvicidal activity of NH-EDx (1000 ppm), n-HDa (5 ppm), and n-ODa (5 ppm) against the A. aegypti and S. litura larvae showed significant mortality rate in a dose-dependent way across all the instars. The larvicidal activity was profound in the A. aegypti as compared to the S. litura across all the larval instars. The sublethal dosages of NH-EDx (500 ppm), n-HDa (2.5 ppm), and n-ODa (2.5 ppm) also showed alterations in the larval/pupal durations and adult longevity in both the insect pests. The enzyme activity revealed that the α- and β-carboxylesterase levels were decreased significantly in both the insect pests, whereas the levels of GST and CYP450 uplifted in a dose-dependent manner of NH-EDx, n-HDa, and n-ODa. Correspondingly, midgut tissues such as the epithelial layer (EL), gut lumen (GL), peritrophic matrix (Pm), and brush border membrane (BBM) were significantly altered in their morphology across both A. aegypti and S. litura against the NH-EDx and their bioactive metabolites. NH-EDx and their bioactive metabolites n-HDa and n-ODa showed significant larvicidal, growth retardant, enzyme inhibition, and midgut toxicity effects against two crucial agriculturally and medically challenging insect pest of ecological importance. [ABSTRACT FROM AUTHOR]

• Larvicidal activity of ethanolic extracts of marine Champia parvula (Ex-Cp) against the dengue mosquito vector Ae. aegypti. • Sub-lethal dosage of Ex-Cp significantly alters the physiological as well as enzyme activity of carboxylesterase (α and β), GST and CYP450. • Ex-Cp displayed significant repellent activity (97%) with maximum level of protection time (210 minutes) at the lethal dosage of 100 ppm. • Non-target toxicity of Ex-Cp against the beneficial aquatic mosquito predators displayed less toxicity. Larval toxicity of ethanolic extract of C. parvula (Ex-Cp) was prominent in the second and the third instars at the maximum lethal dosage of 100 ppm with 98 and 97 % mortality rate respectively. The LC 50 and LC 90 was displayed at 43 ppm and 88 ppm dosage respectively. Correspondingly, the sub-lethal dosage (65 ppm) of Ex-Cp significantly alters the carboxylesterase (α and β), GST and CYP450 enzyme level in both III and IV instar larvae in dose-dependent manner. Similarly, the Ex-Cp displayed significant repellent activity (97 %) with a maximum level of protection time (210 min). Photomicrography assay of Ex-Cp (65 ppm) were toxic to dengue larvae as compared to control. The non-target toxicity of Ex-Cp against the beneficial mosquito predators displayed less toxicity at the maximum dosage of 600 ppm as compared to Temephos. Thus the present research delivers the target and non-target toxicity of red algae C. parvula against the dengue mosquito vector. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative bacterium that induces cell death of macrophages as a key virulence strategy. We have previously demonstrated that the induction of macrophage death is dependent on the host's type I IFN (IFN-I) response. IFN-I signaling has been shown to induce tripartite motif (TRIM) 21, an E3 ubiquitin ligase with critical functions in autoimmune disease and antiviral immunity. However, the importance and regulation of TRIM21 during bacterial infection remains poorly understood. In this study, we investigated the role of TRIM21 upon S. Typhimurium infection of murine bone marrow-derived macrophages. Although Trim21 expression was induced in an IFN-I-dependent manner, we found that TRIM21 levels were mainly regulated posttranscriptionally. Following TLR4 activation, TRIM21 was transiently degraded via the lysosomal pathway by chaperone-mediated autophagy (CMA). However, S. Typhimurium-induced mTORC2 signaling led to phosphorylation of Akt at S473, which subsequently impaired TRIM21 degradation by attenuating CMA. Elevated TRIM21 levels promoted macrophage death associated with reduced transcription of NF erythroid 2-related factor 2 (NRF2)-dependent antioxidative genes. Collectively, our results identify IFN-I-inducible TRIM21 as a negative regulator of innate immune responses to S. Typhimurium and a previously unrecognized substrate of CMA. To our knowledge, this is the first study reporting that a member of the TRIM family is degraded by the lysosomal pathway. [ABSTRACT FROM AUTHOR]

Silica nanoparticles (SNPs) are widely explored as drug carriers, gene delivery vehicles, and as nanoparticles intended for bone and tissue engineering. SNPs are highly evident through various clinical trials for a wide range of biomedical applications. SNPs are biocompatible and promising nanoparticles for next-generation therapeutics. However, despite the well-established importance of SNPs, metabolomics methods for the SNPs remain elusive which renders its maximal clinical translation. We applied 1H nuclear magnetic resonance (1H NMR) spectroscopy to investigate the metabolomics profile in Zebrafish (Danio rerio) exposed to SNPs. Zebrafish were exposed to the SNPs (10.0, 25.0, and 50.0 μg/mL) for 72 h and whole-body samples were subjected for targeted profiling. Pattern recognition of 1H NMR spectral data depicted alterations in the metabolomic profiles between control and SNPs exposed zebrafish. We found that tryptophane, lysine, methionine, phenylalanine, tyrosine, sn-glycero-3-phosphocholine (G3PC), and o-phosphocholine were decreased. The metabolic expression of niacinamide, nicotinamide adenine dinucleotide (NAD+), citrate, adenosine triphosphate (ATP), and xanthine were increased in zebrafish with SNPs treatment. We are report for the first time on metabolite alterations and phenotypic expression in zebrafish via 1H NMR. These results demonstrate that SNPs can adversely affect the significant metabolic pathways involved in energy, amino acids, cellular membrane, lipids, and fatty acid metabolisms. Metabolomics profiling may be able to detect metabolic dysregulation in SNPs-treated zebrafish and establish a foundation for further toxicological studies. [Display omitted] • Silica nanoparticles are biocompatible and induce metabolomic changes. • 1H NMR spectroscopy analysis showed alterations in vital metabolites in zebrafish. • Silica nanoparticles may affect energy, amino acid metabolism, lipids, and fatty acid metabolism. • It can be used to assess metabolomic profile in response to nanomaterials. [ABSTRACT FROM AUTHOR]

Abstract Mosquito that accountable for dispersal of dengue fever is Aedes aegypti Linn. and considered to be a chief vector for dengue especially in South Asian countries. Aspergillus flavus is considered to be wild growing green yellow colonies and synthesis highly regulating aflatoxins (B1, B2, G1 and G2) as a secondary metabolite. Mycotoxins of A. flavus showed its efficacy against III and IV instars of Ae. aegypti with more than 90% mortality at the prominent dosage of 2 × 108 conidia/ml. The proximate lethal concentrations (LC 50 and LC 90) of mycotoxins against third and fourth instars was 2 × 105 and 2 × 107 respectively. Correspondingly, sub-lethal dosage of mycotoxin A. flavus significantly inhibited the level of α- β-carboxylesterase and SOD activity and upregulated the level of major detoxifying enzymes GST and CYP450. Moreover, sub-lethal dosage also showed higher deterrent and fecundity effects. Gut-histological examination reveals that the A. flavus considerably affected the gut epithelial cells along with the inner gut lumen as compared to the control. The non-target screening of A. flavus against two aquatic predators (A. bouvieri and Tx. splendens) display more than 80% of mortality rate against both the species at the dosage of 2 × 1016 (two-fold-higher dosage used in larval assays). Thus the biosafety assessment suggests that A. flavus display higher toxicity against the non-targets and it is not-recommended to apply it directly to the aquatic habitat of dengue mosquito which shares their living space with other beneficial insects. Highlights • Aspergillus flavus fungus against the toxicity of dengue vector and non-target organisms of aquatic predator. • Mycotoxins showed toxicity against III and IV instars of Ae. aegypti with more than 90% mortality at 2 × 108 conidia/ml. • α- β-carboxylesterase and SOD activity was up-regulated the level of major detoxifying enzymes GST and CYP450. • The gut epithelial cells considerably affected along with the inner gut lumen of mosquito vectors. [ABSTRACT FROM AUTHOR]

Epicardial adipose tissue (EAT) has morphological and physiological contiguity with the myocardium and coronary arteries, making it a visceral fat deposit with some unique properties. Under normal circumstances, EAT exhibits biochemical, mechanical, and thermogenic cardioprotective characteristics. Under clinical processes, epicardial fat can directly impact the heart and coronary arteries by secreting proinflammatory cytokines via vasocrine or paracrine mechanisms. It is still not apparent what factors affect this equilibrium. Returning epicardial fat to its physiological purpose may be possible by enhanced local vascularization, weight loss, and focused pharmacological therapies. This review centers on EAT's developing physiological and pathophysiological dimensions and its various and pioneering clinical utilities. [Display omitted] • Damaged EAT can become dangerous and promote thrombosis and inflammation. • PPARγ overexpression in mice heart increases the uptake of fatty acids. • PPARγ activation is cardioprotective in sepsis-induced cardiac dysfunction. • PPARγ signaling may reduce cardiac remodeling. • EAT secretes significantly more adipokines than subcutaneous adipose tissue. [ABSTRACT FROM AUTHOR]

Several proteins and peptides have therapeutic potential and can be used for cancer therapy. By binding to cell surface receptors and other indicators uniquely linked with or overexpressed on tumors compared to healthy tissue, protein biologics enhance the active targeting of cancer cells, as opposed to the passive targeting of cells by conventional small-molecule chemotherapeutics. This study focuses on peptide medications that exist to slow or stop tumor growth and the spread of cancer, demonstrating the therapeutic potential of peptides in cancer treatment. As an alternative to standard chemotherapy, peptides that selectively kill cancer cells while sparing healthy tissue are developing. A mountain of clinical evidence supports the efficacy of peptide-based cancer vaccines. Since a single treatment technique may not be sufficient to produce favourable results in the fight against cancer, combination therapy is emerging as an effective option to generate synergistic benefits. One example of this new area is the use of anticancer peptides in combination with nonpeptidic cytotoxic drugs or the combination of immunotherapy with conventional therapies like radiation and chemotherapy. This review focuses on the different natural and synthetic peptides obtained and researched. Discoveries, manufacture, and modifications of peptide drugs, as well as their contemporary applications, are summarized in this review. We also discuss the benefits and difficulties of potential advances in therapeutic peptides. [Display omitted] • Several proteins and peptides have anticancer potential. • Peptides can be used as a carrier of cytotoxic drugs. • Overexpressed receptors are regulated in cancer treatment. • The preservation of p53 integrity plays a crucial role in preventing tumors. [ABSTRACT FROM AUTHOR]

This review provides a detailed study of pancreatic cancer (PC) and the implication of different types of cancers concerning diabetes. The combination of anti-diabetic drugs with other anti-cancer drugs and phytochemicals can help prevent and treat this disease. PC cancer stem cells (CSCs) and how they migrate and develop into malignant tumors are discussed. A detailed explanation of the different mechanisms of diabetes development, which can enhance the pancreatic CSCs' proliferation by increasing the IGF factor levels, epigenetic modifications, DNA damage, and the influence of lifestyle factors like obesity, and inflammation, has been discussed. It also explains how cancer due to diabetes is associated with high mortality rates. One of the well-known diabetic drugs, metformin, can be combined with other anti-cancer drugs and prevent the development of PC and has been taken as one of the prime focus in this review. Overall, this paper provides insight into the relationship between diabetes and PC and the methods that can be employed to diagnose this disease at an earlier stage successfully. [Display omitted] [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by hepatic accumulation of excess lipids. T cells are commonly classified into various subsets based on their surface markers including T cell receptors, type of antigen presentation and pathophysiological functions. Several studies have implicated various T cell subsets and natural killer (NK) cells in the progression of NAFLD. While NK cells are mainly components of the innate hepatic immune system, the majority of T cell subsets can be part of both the adaptive and innate systems. Several studies have reported that various stages of NAFLD are accompanied by the accumulation of distinct T cell subsets and NK cells with different functions and phenotypes observed usually resulting in proinflammatory effects. More importantly, the overall stimulation of the intrahepatic T cell subsets is directly influenced by the homeostasis of the gut microbiota. Similarly, NK cells have been found to accumulate in the liver in response to pathogens and tumors. In this review, we discussed the nature and pathophysiological roles of T cell subsets including γδ T cells, NKT cells, Mucosal-associated invariant T (MAIT) cells as well as NK cells in NAFLD. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is one of the most common and increasing liver diseases worldwide. NAFLD is a term that involves a variety of conditions such as fatty liver, steatohepatitis, or fibrosis. Gut microbiota and its products have been extensively studied because of a close relation between NAFLD and microbiota in pathogenesis. In the progression of NAFLD, various microbiota-related molecular and cellular mechanisms, including dysbiosis, leaky bowel, endotoxin, bile acids enterohepatic circulation, metabolites, or alcohol-producing microbiota, are involved. Currently, diagnosis and treatment techniques using these mechanisms are being developed. In this review, we will introduce the microbiota-related mechanisms in the progression of NAFLD and future directions will be discussed. [ABSTRACT FROM AUTHOR]

In chronic liver disease, the causative factor is important; however, recently, the intestinal microbiome has been associated with the progression of chronic liver disease and the occurrence of side effects. The immune system is affected by the metabolites of the microbiome, and diet is the primary regulator of the microbiota composition and function in the gut–liver axis. These metabolites can be used as therapeutic material, and postbiotics, in the future, can increase or decrease human immunity by modulating inflammation and immune reactions. Therefore, the excessive intake of nutrients and the lack of nutrition have important effects on immunity and inflammation. Evidence has been published indicating that microbiome-induced chronic inflammation and the consequent immune dysregulation affect the development of chronic liver disease. In this research paper, we discuss the overall trend of microbiome-derived substances related to immunity and the future research directions. [ABSTRACT FROM AUTHOR]