Patients with type 2 diabetes (T2D) have decreased butyrate-producing bacteria. We hypothesized that supplementation with butyrate-producing bacteria may exert beneficial effects on T2D. The current study investigated the effects of well-characterized butyrate-producing bacteria Clostridium butyricum CGMCC0313.1 (CB0313.1) on hyperglycemia and associated metabolic dysfunction in two diabetic mouse models. CB0313.1 was administered daily by oral gavage to leptin ^db/db mice for 5 weeks starting from 3 weeks of age, and to HF diabetic mice induced by high fat diet (HFD) plus streptozotocin (STZ) in C57BL/6J mice for 13 weeks starting from 4 weeks of age. CB0313.1 improved diabetic markers (fasting glucose, glucose tolerance, insulin tolerance, GLP-1 and insulin secretion), and decreased blood lipids and inflammatory tone. Furthermore, CB0313.1 reversed hypohepatias and reduced glucose output. We also found that CB0313.1 modulated gut microbiota composition, characterized by a decreased ratio of Firmicutes to Bacteroidetes, reduced Allobaculum bacteria that were abundant in HF diabetic mice and increased butyrate-producing bacteria. Changes in gut microbiota following CB0313.1 treatment were associated with enhanced peroxisome proliferator–activated receptor-γ (PPARγ), insulin signaling molecules and mitochondrial function markers. Together, our study suggests that CB0313.1 may act as a beneficial probiotic for the prevention and treatment of hyperglycemia and associated metabolic dysfunction.

Numerous nanoparticles drug delivery systems for therapeutic implications in cancer treatment are in preclinical development as conventional chemotherapy has several drawbacks. A chemotherapeutic approach requires high doses of chemotherapeutic agents with low bioavailability, non-specific targeting, and above all, development of multiple drug resistance. In recent years, inorganic nano-drug delivery platforms (NDDPs; with a metal core) have emerged as potential chemotherapeutic systems in oncology. One of the major goals of developing inorganic NDDPs is to effectively address the targeted anti-cancer drug(s) delivery related problems by carrying the therapeutic agents to desired tumors sites. In this current review, we delve into summarizing the recent developments in targeted release of anti-cancer drugs loaded in inorganic NDDPs such as mesoporous silica nanoparticles, carbon nanotubes, layered double hydroxides, superparamagnetic iron oxide nanoparticles and calcium phosphate nanoparticles together with highlighting their therapeutic performance at tumor sites.

The increasing use of pesticides for boosting the yield of agricultural crops also impart toxic residues which ultimately extend to numerous physiological disorders upon consumption. The present study was designed as an effort to assess the reduction potential of various chemical solutions and to minimize the pesticide residues in cauliflower (Brassica oleracea var. botrytis). The samples were soaked in various solutions along with tap water to mitigate pesticide residues. Afterwards, the extracted supernatant was passed through column containing anhydrous sodium sulfate trailed by activated carbon for clean-up. Eluents were first evaporated and then completely dried under gentle stream of Nitrogen. Finally, the residues were determined using gas chromatography equipped with electron capture detector (GC-ECD). Results revealed the highest reduction of endosulfan, bifenthrin and cypermethrin residues with acetic acid (10 %) was 1.133 ± 0.007 (41 %), 0.870 ± 0.022 (60 %) and 0.403 ± 0.003 (75 %), respectively among the tested solutions. However, simple tap water treatment also resulted in 0.990 ± 0.02 (12 %), 1.323 ± 0.015 (14 %) and 1.274 ± 0.002 (21 %) elimination of endosulfan, bifenthrin and cypermethrin residues, respectively. Moreover, among various solutions, acetic acid depicted maximum reduction potential followed by citric acid, hydrogen peroxide, sodium chloride and sodium carbonate solutions. The percent reduction by various solutions ranged from 12 to 41, 14 to 60 and 21 to 75 % for the elimination of endosulfan, bifenthrin and cypermethrin residues, respectively.

Acute pancreatitis (AP) is an inflammatory disorder of the pancreas that can lead to serious systemic complications. Its clinical presentation varies widely, ranging from mild, self-limiting symptoms to severe, life-threatening illness. Currently, there are no specific therapies approved for the treatment of AP, and management primarily relies on supportive care. However, a growing number of clinical trials have evaluated the translational potential of effective therapies derived from experimental models and have identified promising pharmacological agents that may help ameliorate disease severity. Alongside pharmacological approaches, nutritional management of AP has been gaining increasing attention. Evidence supports the use of enteral nutrition over parenteral feeding, as it is associated with a lower risk of necrotic infections, multiple organ dysfunction, mortality, and other associated complications of AP. In this review, we summarize the therapeutic potential of pharmacological and dietary/nutritional interventions, including naturally occurring bioactive compounds, for AP in the context of its molecular pathology, with the aim of supporting improved clinical decision-making, enhancing patient outcomes, and informing future research directions.

Context: The obesity epidemic parallels an increasing type 1 diabetes incidence, such that westernized diets, containing high fat, sugar, and/or protein, through inducing nutrient-induced islet β-cell stress, have been proposed as contributing factors. The broad-spectrum neutral amino acid transporter (B0AT1), encoded by Slc6a19, is the major neutral amino acids transporter in intestine and kidney. B0AT1 deficiency in C567Bl/6J mice causes aminoaciduria, lowers insulinemia, and improves glucose tolerance. Objective: We investigated the effects of standard rodent chow (chow), high-fat high-sucrose (HFHS), and high-fat high-protein (HFHP) diets, in addition to B0AT1 deficiency, on the diabetes incidence of male nonobese diabetic (NOD/ShiLtJArc (NOD)) mice. Methods: Male NOD.Slc6a19+/+ and NOD.Slc6a19−/− mice were fed chow, HFHS and HFHP diets from 6 to 24 weeks of age. A separate cohort of male NOD mice were fed the three diets from 6-30 weeks of age. Body weight and fed-state blood glucose and plasma insulin were monitored, and urinary amino-acid profiles, intraperitoneal glucose tolerance, diabetes incidence, pancreatic islet number, insulitis scores and beta-cell mass were measured. Results: The incidence of diabetes and severe glucose intolerance was 3.8% in HFHS-fed, 25.0% in HFHP-fed, and 14.7% in chow-fed mice, with higher pancreatic islet number and lower insulitis scores in HFHS-fed mice. B0AT1 deficiency had no effect on diabetes incidence, but curtailed HFHS-induced excessive weight gain, adipose tissue expansion, and hyperinsulinemia. In HFHP-fed mice, B0AT1 deficiency significantly increased pancreatic β-cell clusters and small islets. Male NOD mice that did not develop autoimmune diabetes were resistant to diet-induced hyperglycemia. Conclusion: Dietary composition does, but B0AT1 deficiency does not, affect autoimmune diabetes incidence in male NOD mice. B0AT1 deficiency, however, reduces diet-induced metabolic dysfunction and in HFHP-fed mice increases pancreatic β-cell clusters and small islets.

Aims/hypothesis: Heterogeneity in the pathophysiology of type 2 diabetes is increasingly being realised. The currently available rodent models of type 2 diabetes all have limitations and do not accurately reflect all human type 2 diabetes subtypes. NOD.BR- H2 ^k /Wicker mice (NOD ^k ), derived from the non-obese diabetic (NOD) mouse, are type 1 diabetes resistant. However, transgene induced beta-cell stress in male NOD ^k mice induces hyperinsulinaemia followed by diabetes. Here we have investigated the propensity of NOD ^k mice to develop a Western-diet (WD) induced hyperinsulinaemic subtype of type 2 diabetes. Comparator mouse strains used were BALB/c and B10.BR- H2 ^k /SgSnJ mice (B10 ^k ). Methods: In the longer-term studies (14-24 weeks), NOD ^k , B10 ^k and BALB/c mice were randomised to receive Chow or WD from 4 weeks of age, followed by serial measurement of body weight and fed-state blood glucose. IPGTT and IPITT tests were conducted at 13 weeks of age. Blood and pancreas were harvested for further analyses at 14 and 24 weeks of age, or sooner if diabetes developed (blood glucose concentrations ≥20 mmol/l on two consecutive days). In the acute studies, metabolic characteristics of the three strains at 8 weeks of age, continued on Chow or after a 5-day WD challenge (WDC) were assessed, along with harvesting pancreas on day 5 for ex vivo islet insulin secretion, electron microscopy, and bulk islet transcriptomics analyses. Results: Male WD-fed NOD ^k mice became markedly hyperinsulinaemic, gained excess weight and developed a severe type 2 diabetes phenotype. Emergence of diabetes was associated with islet endocrine cell apoptosis and loss of beta-cell mass, without evidence of insulitis. Insulin resistance on IPITT testing, however, was not evident in Chow-fed NOD ^k mice. In contrast, male B10 ^k mice already had poor glucose tolerance on Chow diet and, despite having a hypoinsulinaemic phenotype, were resistant to WD-induced diabetes. BALB/c mice developed very mild glucose intolerance and hyperinsulinaemia in response to the WD. Female NOD ^k mice were diabetes resistant. At 8 weeks of age, male Chow-fed NOD ^k mice were mildly hyperinsulinaemic despite relative hypoglycaemia compared to the other strains. The acute 5-day WDC markedly increased hyperinsulinaemia in NOD ^k mice. Transcriptomics analyses identified robust strain-specific differences, including altered islet cell differentiation, energy metabolism, endoplasmic reticulum to golgi vesicle transport and insulin processing. Conclusions/interpretation: NOD ^k mice, which exhibit mild hyperinsulinaemic hypoglycaemia on Chow diet and rapidly develop marked hyperinsulinaemia on WD, are type 2 diabetes prone. In contrast, B10 ^k mice have poor glucose tolerance on Chow diet and no or limited capacity to increase insulinaemia in response to WD, are diabetes resistant. These findings support the hypothesis that hyperinsulinaemia is upstream to insulin resistance in the pathogenesis of severe insulin resistant subset of type 2 diabetes for which the WD-fed NOD ^k mouse is a suitable new mouse model. Research in Context: What is already known about this subject?: Which of insulin hypersecretion and insulin resistance are upstream in the pathogenesis of the severe insulin resistant subtype of type 2 diabetes continues to be debated Rodent models of type 2 diabetes do not accurately reflect all human subtypes of type 2 diabetes NOD ^k mice, derived from the non-obese diabetic (NOD) mouse, are type 1 diabetes resistant, but with transgene induction of islet beta-cell stress develop hyperinsulinaemia, followed by type 2 diabetes What is the key question?: Could Western-diet fed NOD ^k mice be developed as a model of severe insulin resistant type 2 diabetes and shed light on its upstream pathogenesis? What are the new findings?: Male NOD ^k mice tend to hyperinsulinaemic hypoglycaemia on Chow diet, rapidly develop marked hyperinsulinaemia on Western-diet feeding, and then develop type 2 diabetes Male B10 ^k mice (one of two comparator strains (B10 ^k and BALB/c)) have poor glucose tolerance on Chow diet, limited capacity to increase insulinaemia in response to Western-diet feeding, but are resistant to develop Western-diet induced type 2 diabetes Isolated islet findings show strain differences that favour intrinsic hyper-responsiveness and hypo-responsiveness of islet beta-cells of NOD ^k and B10 ^k mice, underpinning their respective metabolic phenotypes How might this impact on clinical practice in the foreseeable future? The findings are in support of the insulin hypersecretion hypothesis for severe insulin resistant type 2 diabetes, such that therapies to limit islet beta-cell hyperresponsiveness to prevent and treat this subtype of diabetes warrant investigation