Sirtuin 1 and 7 mediate resveratrol-induced recovery from hyper-anxiety in high-fructose-fed prediabetic rats

Hyperglycaemia in diabetes is either caused by reduced availability of insulin (type 1 diabetes, T1D) or insulin resistance to the cells (type 2 diabetes, T2D). In recent years, the prevalence of T2D has increased to an alarming proportion, encompassing 95% of the total diabetic burden, probably due to economy-driven changes in lifestyle. Recent epidemiological studies show comorbid depression, anxiety and related mental illness. To explore the molecular mechanisms underlying this comorbid conditions, we used Sprague–Dawley rats on high-fructose diet for 8 weeks to induce prediabetic condition. Rats with this metabolic syndrome also showed hyper-anxiety when they were subjected to anxiety-related behavioural assays. Rats were administered with resveratrol, an activator of sirtuins, and metformin, a standard antidiabetic drug, simultaneously with fructose. We observed that resveratrol was more effective in protecting from both the metabolic (prediabetic) and affective (anxiety) disorders than metformin. Molecular studies showed that recovery was associated with the upregulation of few nuclear sirtuins that act epigenetically – Sirt 1 and 7, which were significantly attenuated in the striatum of prediabetic rats. In conclusion, our study showed that hyper-anxiety associated with prediabetic condition is ameliorated by resveratrol through modulation of sirtuins, which is more or less similar to metformin.     

Natural Progression of Canine Glycogen Storage Disease Type IIIa

Glycogen storage disease type IIIa (GSD IIIa) is caused by a deficiency of glycogen debranching enzyme activity. Hepatomegaly, muscle degeneration, and hypoglycemia occur in human patients at an early age. Long-term complications include liver cirrhosis, hepatic adenomas, and generalized myopathy. A naturally occurring canine model of GSD IIIa that mimics the human disease has been described, with progressive liver disease and skeletal muscle damage likely due to excess glycogen deposition. In the current study, long-term follow-up of previously described GSD IIIa dogs until 32 mo of age (n = 4) and of family-owned GSD IIIa dogs until 11 to 12 y of age (n = 2) revealed that elevated concentrations of liver and muscle enzyme (AST, ALT, ALP, and creatine phosphokinase) decreased over time, consistent with hepatic cirrhosis and muscle fibrosis. Glycogen deposition in many skeletal muscles; the tongue, diaphragm, and heart; and the phrenic and sciatic nerves occurred also. Furthermore, the urinary biomarker Glc₄, which has been described in many types of GSD, was first elevated and then decreased later in life. This urinary biomarker demonstrated a similar trend as AST and ALT in GSD IIIa dogs, indicating that Glc₄ might be a less invasive biomarker of hepatocellular disease. Finally, the current study further demonstrates that the canine GSD IIIa model adheres to the clinical course in human patients with this disorder and is an appropriate model for developing novel therapies.Abbreviations: CCR, curly-coated retriever; CPK, creatine phosphokinase; GSD IIIa, glycogen storage disease type IIIa; Glc₄, Glcα1-6Glcα1-4Glcα1-4GlcGlycogen storage disease type IIIa (GSD IIIa; OMIM, 232400) is an autosomal recessive disorder caused by mutations in the glycogen debranching enzyme gene (AGL), leading to various clinical signs. The tissues mainly affected are liver, heart, and skeletal muscle. Clinical manifestations include hypoglycemia, elevated serum concentrations of liver and muscle enzymes, hepatomegaly, growth retardation, muscle weakness, cardiac hypertrophy with arrhythmia risk, polycystic ovaries and neuropathy.^15,17,29 Current treatments are mainly symptomatic and are not curative. The most frequently used therapies are dietary, such as providing uncooked corn starch to prevent hypoglycemia at young ages and high-protein diets, which have been shown to reverse the extent of cardiomyopathy associated with GSD IIIa.^7,8,30,37 In addition, the use of medium-chain triglycerides has shown positive therapeutic effects in patients with GSD Ia and GSD IIIa.^11,22 However, dietary therapies do not prevent the long-term complications of GSD IIIa, including hepatic cirrhosis, hepatocellular adenoma, hepatocellular carcinoma, cardiomyopathy, neuropathy, and myopathy.³¹An appropriate animal model is necessary to test novel therapies and address the long-term effects of GSD IIIa. Recently a mouse model for GSD III has been described that may prove beneficial in testing new therapies.¹⁹ However, the limitations of mouse models include a short lifespan that curtails the study of the long-term effects of novel treatments. In addition, a large animal model often mimics human disease more closely than do mouse models, as occurs in GSD type Ia dog models, which exhibit lactic acidosis similar to human patients, a characteristic that mouse models of GSD Ia lack.¹⁶ Therefore a naturally occurring large animal model for GSD IIIa may be more effective in terms of the development of new treatments than are available mouse models.GSD IIIa (OMIA, 001577) has been reported to occur in curly-coated retriever dogs (CCR) and is caused by a naturally occurring homozygous frameshift mutation in exon 32 that leads to the deletion of 126 amino acids at the C-terminus of glycogen debranching enzyme.^12,40 The dogs in these previous studies proved to have abnormalities similar to those seen in humans affected with the disorder, namely progressive glycogen accumulation in muscle and liver, elevated liver and muscle enzymes (ALP, AST, creatine phosphokinase [CPK], and ALT), and eventual liver fibrosis. However, these animals were not followed beyond 16 mo of age in the earlier studies.^12,40 The goal of the current study is to provide biochemical follow-up on these animals and analyze more extensively other tissues and organs involved in GSD IIIa in the dog model. A brief analysis of the naturally high protein diets of GSD IIIa dogs, as well as the effects of an increased protein diet in 2 dogs for the last few months of life, is included.We also include the analysis of a urinary biomarker, Glcα1–6Glcα1– 4Glcα1–4Glc (Glc₄), which is a breakdown product of glycogen by α-amylase and neutral α-1,4-glucosidase.³² Elevated levels of Glc₄ have been found in urine from patients with GSD types II, III, IV, VI, and IX and may correlate with disease advancement.^1,18,24,32 To our knowledge, Glc₄ has not been evaluated previously in dogs; we therefore here evaluated the utility of Glc₄ as a biomarker of canine GSD IIIa. A correlation of Glc₄ levels with liver enzyme concentrations in blood might indicate a role of Glc₄ as a less-invasive biomarker for determining the advancement of liver disease in human and canine patients.     

Interaction of Catechu Dye with DNA: Spectroscopic and In Silico Approach

Catechin, a yellow colored molecule obtained from the wood of Acacia catechu was analyzed for its interaction with synthetic DNA duplexes using spectroscopic analysis. UV-Visible spectroscopic analysis revealed the non-intercalative binding mode. Fourier Transform Infrared spectroscopy (FTIR) analysis expose chemical shift indicated by various vibrational stretches and an increase in the intensity of base stacking was observed by Circular Dichroism (CD), respectively. This inference was further confirmed through nuclear staining technique and also in electrophoretic technique; the dye quenches the fluorescent intensity of ethidium bromide. The result of fluorescence spectroscopy was in concordance with the electrophoretic technique. In addition, the spectroscopic results were in accordance with the molecular docking studies of specific catechin compound from the catechu dye with CT-DNA. This kind of site specificity is a gain in the medicinal field as the drug can be DNA targeted for cancer therapeutics. The present work reveals that catechu dye has a noteworthy application in the field of medical bioscience.     

Melanin–Perovskite Composites for Photothermal Conversion

Biomacromolecular pigments, such as melanin, play an essential role in the survival of all living beings. Melanin absorbs sunlight and transforms it into heat, which is crucial for avoiding damage to skin cells. Light absorption produces excited electrons, which could either fall back to ground states by releasing the heat (photothermal effect) and/or light (photoluminescence), or stay at higher energy levels within its lifetime period, which can be captured through external electronic circuitry (photovoltaic effect). In this study, it is demonstrated that the combination of melanin with halide perovskite light absorber in the form of a composite exhibits high absorbance from the UV to NIR region in the solar spectrum. And the composite displays significantly reduced photoluminescence and minimized density of residual excited states (verified by photovoltaic measurement) owing to the significantly enhanced nonradiant quenching by the melanin. As a result, the composite shows an ultrahigh solar‐thermal quantum yield of 99.56% and solar‐thermal conversion efficiency of ≈81% under one‐sun illumination (AM1.5), which is superior to typical carbon materials such as graphene (≈70%). By coating the photothermal composite film on the hot‐side of thermoelectric devices, a 7000% increase in output power as compared to the blank device under illumination is observed.     

Semiochemical footprints of the predaceous coccinellid beetle,Menochilus sexmaculatus,deter Zygogramma bicolorata (Coleoptera: Chrysomelidae) from feeding on Parthenium

Present study assessed if semiochemical cues left by an aphidophagous beetle, M. sexmaculatus influenced foraging behaviour of a phytophagous beetle, Z. bicolorata on noxious weed, P. hysterophorus. The lower predation attributes of Z. bicolorata in presence of M. sexmaculatus semiochemical footprints confirms they interfere with weed biological control.     

Zingerone induced caspase‐dependent apoptosis in MCF‐7 cells and prevents 7,12‐dimethylbenz(a)anthracene‐induced mammary carcinogenesis in experimental rats

Breast cancer is a prevalent of tumoregenesis in women and reports for the maximum mortality and morbidity in the global. Ginger (Zingiber officinale) is the mainly widespread spice and herbal remedies used in the world. Since antique periods, ginger has been used in Greece, India and China for the curing of upset stomach, nausea, diarrhea, colds, and headaches. The current work was planned to explore the anticancer properties of zingerone (ZO) toward 7,12‐dimethylbenz(a)anthracene (DMBA)‐treated mammary carcinogenesis in Sprague‐Dawley (SD) rats and MCF‐7 mammary cancer cells. The mammary carcinogenesis was produced through a single dosage of DMBA (20 mg/kg bwt) mixed in soya oil (1 mL) administrated intragastrically with a gavage. We found improved concentrations of lipid peroxidation (LOOH and TBARS), carcinoembryonic antigen, lowered levels of enzymatic (CAT, GPx, and SOD), and nonenzymatic (vitamin E, GSH, and vitamin C) antioxidant in mammary tissues and plasma of DMBA‐induced cancer bearing animals. Moreover, augmented concentrations of phase I (Cyt‐b₅ and CYP₄₅₀) and reduced levels of phase II (GR and GST) detoxification microsomal proteins in mammary tissues were noticed. ZO administrations significantly reverted back to all these parameters in this way, showing efficient of anticancer effect. Furthermore, our in vitro study also supported the anticancer effect of the treatment of ZO were noticed loss of cell viability, improved reactive oxygen species formation, and reduced MMP. Furthermore, the status of apoptosis proteins such as Bcl‐2, Bax, and Bid expressions was determined by using Western blot analysis techniques. Overall, these results proposed the anticancer effect of ZO toward DMBA‐induced mammary cancer in SD animals and Michigan cancer foundation‐7 mammary cancer cells.     

A ginger derivative,zingerone—a phenolic compound—induces ROS‐mediated apoptosis in colon cancer cells (HCT‐116)

Zingerone (ZO), an active phenolic agent derived from Zingiber officinale (Ginger), has many pharmacological properties such as antioxidant, antiangiogenic, and antitumor. However, its potential value in cancer and the mechanism by which ZO wields its therapeutic effects remain obscure. Therefore, in this current study, we explored the effects of ZO on suppressing cell proliferation and enhancing apoptosis in colon cancer cells (HCT116). Our results indicated that ZO significantly enhances the production of reactive oxygen species, lipid peroxidation (thiobarbituric acid reactive substance [TBARS]), and loss of cell viability; and reduces mitochondrial membrane potential and antioxidant levels (SOD, CAT, and GSH) in ZO‐treated HCT116 cells in a dose‐dependent (2.5, 5, and 10 µM) manner. Furthermore, ZO induces oxidative stress‐mediated apoptosis as evidenced by apoptotic morphological changes predicted by AO/EtBr, Hoechst staining and further confirmed by comet assay. Moreover, immunoblotting techniques showed that ZO treatment effectively enhances Bax, caspase‐9, and caspase‐3 expressions and decreases the expression of Bcl‐2 in colon cancer cells. Together, our results evidenced that the antitumor effects of ZO reduce cell proliferation and stimulate apoptosis through modulating pro‐ and antiapoptotic molecular events in HCT116 colon cancer cells. Therefore, based on our findings, ZO may be used as a therapeutic agent for the treatment of colon cancer.     

Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology

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Developmental signals do not further accentuate nonuniform postpneumonectomy compensatory lung growth.

Mechanical forces imposed on lung tissue constitute major stimuli for normal lung development and postpneumonectomy (PNX) compensatory growth and remodeling. Superimposing developmental signals on PNX signals augments compensatory alveolar growth but exaggerates airway-parenchymal dissociation (i.e., dysanaptic lung growth); the latter tends to offset benefits derived from the former. In adult dogs after PNX, lobar expansion and growth of the remaining lobes were markedly non-uniform (Ravikumar et al. J Appl Physiol 97:1567-1574, 2004). We hypothesized that superimposing developmental and post-PNX signals further accentuates nonuniformity of lobar growth. We used high-resolution computed tomography (HRCT) to follow regional lung expansion and growth in foxhounds undergoing right PNX at 2.5 mo of age compared with litter-matched control (Sham) animals; scans were performed 4 and 10 mo following surgery, i.e., before and after somatic maturity. Air and tissue volumes were measured in each lobe; tissue volume estimated by HRCT includes air-free tissue and blood in small vessels <1 mm. Interlobar nonuniformity of tissue volume was absent at 4 mo but evident 10 mo after PNX; growth of the remaining left lower lobe gradually lagged behind other lobes. At maturity, nonuniformity of lobar growth in pneumonectomized puppies was similar to that previously reported in pneumonectomized adults. We conclude that superimposing developmental and post-PNX signals enhances some aspects of compensatory lung growth and remodeling without altering its nonuniform spatial distribution.