Oil-Gan, also known as emblica, is the fruit of the genus Phyllanthus emblica L. The fruits of these trees are high in nutrients and have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN from throughout the disease course. The primary aim of this study was to examine the protective effects (including urine analyses, the measurement of inflammatory cytokine levels, and histological examination) and mechanisms of action of an ethyl acetate extract of P. emblica (EPE) on db/db mice, an animal model of diabetic nephropathy, as well as a secondary aim of examining the expression levels of protein kinase Cα (PKCα) in the kidney and its downregulation of vascular endothelial growth factor (VEGF) and fibrosis gene transforming growth factor-β1 (TGF-β1) by Western blot analyses. Eight db/m C57BLKS/J mice were used as the control group. Forty db/db mice were randomly divided into five groups. Treatments included vehicle, EPE1, EPE2, EPE3 (at doses of 100, 200, or 400 mg/kg EPE), or the comparative drug aminoguanidine for 8 weeks. After 8 weeks of treatment, blood samples were collected for analyses of blood glucose, insulin, and HbA1c levels, and pancreatic and kidney tissues were dissected for histological analyses. The present study indicated that the administration of EPE to db/db mice effectively controlled hyperglycemia and hyperinsulinemia by markedly lowering blood glucose, insulin, and glycosylated HbA1c levels. Administration of EPE to db/db mice decreased the levels of BUN and creatinine both in blood and urine and reduced urinary albumin excretion and the albumin creatine ratio (UACR) in urine. Moreover, EPE treatment decreased the blood levels of inflammatory cytokines, including kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), and NLR family pyrin domain containing (NLRP3). Our findings showed that EPE not only had antihyperglycemic effects but also improved renal function in db/db mice. Histological examination of the kidney by immunohistochemistry indicated that EPE can improve kidney function by ameliorating glomerular morphological damage following glomerular injury; alleviating proteinuria by upregulating the expression of nephrin, a biomarker of early glomerular damage; and inhibiting glomerular expansion and tubular fibrosis. Moreover, the administration of EPE to db/db mice increased the expression levels of p- PKCα/t-PKCα but decreased the expression levels of VEGF and renal fibrosis biomarkers (TGF-β1, collagen IV, p-Smad2, p-Smad3, and Smad4), as shown by Western blot analyses. These results implied that EPE as a supplement has a protective effect against renal dysfunction through the amelioration of insulin resistance as well as the suppression of nephritis and fibrosis in a DN model.

Memory and emotion are highly vulnerable to psychiatric disorders like post-traumatic stress disorder (PTSD), which has been linked to serotonin (5-HT) metabolism disruptions. In fact, over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) meta-bolic pathway, producing a variety of bioactive molecules. The aadat (kat2) gene encodes mito-chondrial kynurenine aminotransferase (KAT) isotype 2, responsible for kynurenic acid (KYNA) production. Little is known about its role in behavior. In CRISPR/Cas9-induced aadat knockout (kat2−/−) mice, we examined the effects on emotion, memory, motor function, Trp and its metabolite levels, enzyme activities in the plasma and the urine of 8-week-old males compared to wild-type mice. Transgenic mice showed more depressive-like behaviors in the forced swim test, but not in the tail suspension, anxiety, or memory tests. They also had fewer center field and corner entries, shorter walking distances, and fewer jumping counts in the open field test. Plasma metabolite levels are generally consistent with those of urine: KYN, antioxidant KYNs, 5-hydroxyindolacetic acid, and indole-3-acetic acid levels are lower; enzyme activities in KATs, kynureninase, and monoamine oxidase/aldehyde dehydrogenase are lower, but kynurenine 3-monooxygenase is higher; and ox-idative stress and excitotoxicity indices are higher. Transgenic mice show depression-like behavior in a learned helplessness model, emotional indifference, and motor deficits, coupled with a decrease in KYNA, a shift of Trp metabolism toward the KYN-3-HK pathway, and a partial decrease in the gut microbial Trp-indole pathway metabolite. This is the first evidence that deleting the aadat gene causes depression-like behaviors that are unique to despair experience, which appears to be linked to excitatory neurotoxic and oxidative stresses. This may lead to the development of a double-hit preclinical model in experience-based depression, better understanding of these complex condi-tions, and more effective therapeutic strategies by elucidating the relationship between Trp me-tabolism and PTSD pathogenesis.

Dietary fibers regulate intestinal barrier function; however, the precise mechanisms remain unclear. This study investigated the effects of psyllium fibers on antimicrobial protein expression, focusing on the type II immunity and tuft cell-group 2 innate lymphoid cell (ILC2) circuit in the small intestine of the mouse. Supplemental psyllium fiber upregulated antimicrobial proteins, such as small proline-rich protein 2A (SPRR2A) and resistin-like beta (RELMβ), in mouse small intestine, evidently affecting cecal microbiota composition. Psyllium fibers also increased the RNA and protein expression of molecules related to ILC2 and tuft cells, such as IL-13, IL-25, DCLK1, Gfi-1b, SH2 domain-containing protein 3C, and Spi-B. In addition, ILC2 inhibitor (disulfiram) and bitter taste receptor blocker administration reduced psyllium-induced SPRR2A and RELMβ expression. Collectively, psyllium supplementation upregulates antimicrobial proteins such as SPRR2A and RELMß via the type II immune response and tuft cell-ILC2 circuit in the mouse small intestine.

This study investigates the effects of xylitol, a natural sugar alcohol, on tumor progression in syngeneic mouse cancer models. Xylitol has been known for its dental health benefits, but emerging evidence suggests broader biological roles, including potential anti-cancer properties. We explored xylitol's impact on two mouse cancer models: 4T1 mammary carcinoma and B16F10 melanoma. Xylitol's efficacy in inhibiting cancer cell lines and modulating tumor progression was assessed using immunocompetent female mice. The experiments involved intratumoral and peri-tumoral administration of a 20% xylitol solution in two mouse strains: BALB/c (4T1 mammary carcinoma) and C57BL/6 (B16F10 melanoma). Tumor volume, histopathology, and metabolomic analyses were conducted to gauge xylitol's influence. The study revealed that xylitol administration initially reduced tumor growth in the B16F10 melanoma model, accompanied by alterations in tumor metabolism. However, similar effects were not observed in the 4T1 mammary carcinoma model, and melanoma tumor growth re-commenced after stroma deterioration permitted xylitol solution leakage. These findings suggest that xylitol may have potential as an adjunct therapy in cancer treatment, specifically in melanoma. The differential response between the two cancer models underscores the complexity of cancer biology and the need for further investigation into xylitol's mechanisms of action and its role in cancer therapy.