Changes in Nutritional Status of Cancer Patients Undergoing Proton Radiation Therapy Based on Real-World Data.

Methods: Observational study on 47 adult hospitalized cancer patients including 27 males and 20 females who received proton beam radiotherapy during December 2021 and August 2022. Nutritional assessments, 24 h dietary survey, handgrip strength (HGS) test, anthropometrical measurements, and hematological parameters were conducted or collected at the beginning and the completion of treatment. Results: The rate of nutritional risk and malnutrition among the total of 47 enrolled patients was 4.3% and 12.8% at the onset of proton radiation and raised up to 6.4% and 27.7% at the end of the treatment. 42.6% of patients experienced weight loss during the proton radiotherapy, and 1 of them had weight loss over 5%, and in general, the average body weight was stable over radiotherapy. The changes in patients' 24 h dietary intakes, HGS, and anthropometrical parameters, including triceps skinfold thickness (TSF), midupper arm circumference (MUAC), and midupper arm muscle circumference (MAMC), were statistically insignificant over the treatment (all p values > 0.05). The changes in patients' hematological parameters, including total protein (TP) and serum albumin (ALB), were not statistically significant over the treatment (all p values >0.05), and the level of hemoglobin (HGB) at the end of treatment was higher than that at the onset (p < 0.05). Conclusion: The results of this study demonstrated that proton radiotherapy might have a lighter effect on the nutritional status of cancer patients.

Andrographolide ameliorates hepatic steatosis by suppressing FATP2-mediated fatty acid uptake in mice with nonalcoholic fatty liver disease.

Excessive intrahepatocellular lipid accumulation or steatosis is caused by abnormal lipid metabolism and a common character of nonalcoholic fatty liver disease (NAFLD), which may progress into cirrhosis and hepatocellular cancer. Andrographolide (Andro) is the primary active ingredient extracted from Andrographis paniculata, showing a protective role against dietary steatosis with the mechanism not fully understood. In this study, we showed that administration of Andro (50, 100, and 200 mg/kg/day for 8 weeks, respectively) attenuated obesity and metabolic syndrome in high-fat diet (HFD)-fed mice with improved glucose tolerance, insulin sensitivity, and reduced hyperinsulinemia, hyperglycemia, and hyperlipidemia. HFD-fed mice presented hepatic steatosis, which was significantly prevented by Andro. In vitro, Andro decreased the intracellular lipid droplets in oleic acid-treated LO2 cells. The selected RT-PCR array revealed a robust expression suppression of the fatty acid transport proteins (FATPs) by Andro treatment. Most importantly, we found that Andro consistently reduced the expression of FATP2 in both the oleic acid-treated LO2 cells and liver tissues of HFD-fed mice. Overexpression of FATP2 abolished the lipid-lowering effect of Andro in oleic acid-treated LO2 cells. Andro treatment also reduced the fatty acid uptake in oleic acid-treated LO2 cells, which was blunted by FATP2 overexpression. Collectively, our findings reveal a novel mechanism underlying the anti-steatosis effect of Andro by suppressing FATP2-mediated fatty acid uptake, suggesting the potential therapeutic application of Andro in the treatment of NAFLD.

The Herbal Formula Granule Prescription Mahuang Decoction Ameliorated Chronic Kidney Disease Which Was Associated with Restoration of Dysbiosis of Intestinal Microbiota in Rats.

Chronic kidney disease (CKD) has become a global health issue, and there is increasing evidence showing the beneficial roles of traditional Chinese medicine (TCM) in CKD treatment. Here, we studied the renoprotective role of Mahuang decoction, a famous TCM prescription, in a rat CKD model induced with the combination of doxorubicin and adenine. Our data showed that intragastric administration of Mahuang decoction inhibited the loss of bodyweight and attenuated proteinuria, serum creatinine, and blood urea nitrogen in CKD rats. Kidney histological analysis revealed decreased tubulointerstitial injury and fibrosis in CKD rats treated with Mahuang decoction accompanied with suppressed expression of TGF-ß1 and phosphorylated NF-κB/P65 (p-P65) as indicated by immunohistochemistry. ELISA analysis demonstrated reduced serum levels of proinflammatory cytokines TNFα and IL-6. Most importantly, intestinal microbiota analysis by 16s rRNA-seq showed that Mahuang decoction restored the impaired richness and diversity of intestinal microflora and recovered the disrupted microbial community through reducing the abundance of deleterious microbes and promoting the expansion of beneficial microbes in CKD rats. Collectively, our findings demonstrated that Mahuang decoction mitigated kidney functional and structural impairment in CKD rats which were associated with the restoration of dysbiosis of intestinal microbiota, implying its potential in clinical CKD treatment.

Tetrandrine ameliorated Alzheimer's disease through suppressing microglial inflammatory activation and neurotoxicity in the 5XFAD mouse.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder prevalent in the aged population. Tetrandrine is a natural metabolite isolated from herbal medicine Stephania tetrandra with various activities. PURPOSE: In this study, we investigated the therapeutic role of tetrandrine in 5XFAD mouse, a transgenic model of AD. METHODS: 5XFAD mice were intraperitoneally injected with saline or different doses of tetrandrine (10, 20, and 40 mg/kg per 2 days) from the age of 5 months to 7 months followed by the determination of cognitive ability, amyloid plaque load, cell apoptosis, and inflammation in the brain. In vitro, the protective roles of tetrandrine against inflammatory activation of microglia and the resulting neurotoxicity were studied in BV2 cells and differentiated PC12 cells, respectively. RESULTS: Morris water maze test showed that two months of tetrandrine treatment dose-dependently improved the cognitive ability of 5XFAD mice. Immunostaining against Aß 1-42 demonstrated reduced amyloid plaque deposition in the brain of tetrandrine-treated 5XFAD mice. TUNEL assay revealed decreased cell apoptosis in the hippocampus after tetrandrine treatment. Further, RT-PCR showed that the ectopic transcription of inflammation-associated genes including TNFα, IL-1ß, IL-6, COX-2, iNOS, and p65 was reversed in 5XFAD mice treated with tetrandrine. In vitro, Aß 1-42 stimulated the secretion of inflammatory cytokines TNFα and IL-1ß in microglial BV2 cells as determined by ELISA, which was suppressed by tetrandrine pre-treatment. Tetrandrine pre-treatment also inhibited the expression of TLR4, p65, iNOS, and COX-2 in BV2 cells induced by Aß 1-42. Most importantly, treatment of PC12-derived neuron-like cells with conditional medium from Aß 1-42-stimulated BV2 cells remarkably impaired cell viability and promoted cell apoptosis, which was attenuated by the conditional medium from BV2 cells with tetrandrine pre-treatment. CONCLUSION: Collectively, findings in this study demonstrated that tetrandrine ameliorates AD by suppressing microglia-mediated inflammation and neurotoxicity.

Curcumin relieved cisplatin-induced kidney inflammation through inhibiting Mincle-maintained M1 macrophage phenotype.

BACKGROUND: Acute kidney injury (AKI) is a common kidney disease with a high risk of death and can develop into chronic kidney disease (CKD) and renal failure eventually. Curcumin, an herbal supplement, has been reported exhibiting a renoprotective role in AKI. However, the underlying mechanism is largely unclear. PURPOSE: Recent research showed that Mincle (Macrophage-inducible C-type lectin) maintained M1 macrophage polarization, which plays a key role in kidney injury of AKI through up-regulating the expression and secretion of inflammatory cytokines. Here, we investigated the effects of Curcumin on Mincle expression and macrophage polarization in vitro using lipopolysaccharide (LPS) induced macrophage inflammatory cell model and in vivo using a cisplatin induced murine AKI (cis-AKI) model. METHODS: Cell activation, inflammatory cytokines expression and secretion, protein levels, macrophage polarization and renal pathology were analyzed. RESULTS: Our results showed that Curcumin markedly reduced the mRNA expression and secretion of IL-1ß, IL-6, TNFα and MCP-1 in LPS stimulated RAW264.7 cell and the supernatant. The same results were found in Curcumin treated cis-AKI kidney and blood. The data also demonstrated that Curcumin remarkably down-regulated mRNA expression and protein level of Mincle in cis-AKI kidney and also reduced expression of iNOS (M1 macrophage marker) as well as inhibited the activation of Syk and NF-kB. Interestingly, although Mincle deletion in RAW264.7 cell largely decreased the LPS-induced protein level of iNOS, Curcumin cannot further reduce expression of iNOS without Mincle, indicating that Curcumin inhibits M1 macrophage with a Mincle-dependent pattern. Furthermore, flow cytometry results showed that Curcumin significantly decreased the iNOS positive macrophages and increased the CD206 (M2 macrophage marker) positive macrophages in vivo and in vitro. CONCLUSION: Our findings prove that Curcumin protects kidney from cisplatin induced AKI through inhibiting Mincle maintained M1 macrophage phenotype, that may provide a specific renoprotection mechanism for Curcumin to develop it as a new therapeutic candidate for AKI.

Decursin inhibits the growth of HepG2 hepatocellular carcinoma cells via Hippo/YAP signaling pathway.

Targeted therapy has a pivotal role for the treatment of liver cancer. The aim of this current study was to examine the effects of decursin on the growth of HepG2 cells and the underlying mechanisms. Our present study showed that treatment of HepG2 cells with decursin significantly inhibited the growth of HepG2 cells by suppressing cell proliferation, cell cycle arresting, and promoting apoptosis in a dose- and time-dependent manner. Most significantly, administration of decursin dramatically impeded in vivo tumor growth in nude mice. Mechanically, it is noteworthy that decursin treatment provoked degradation of YAP by upregulating the expression of phosphorylated LATS1 and ßTRCP. Moreover, apoptosis caused by decursin could be reversed by a selective MST1/2 inhibitor, XMU-MP-1, suggesting that decursin may function through Hippo/YAP signaling. This study has identified that decursin is a potential agent for HCC therapy, and further research should be undertaken to facilitate its therapeutic application.

Ethanol Extract of Root of Prunus persica Inhibited the Growth of Liver Cancer Cell HepG2 by Inducing Cell Cycle Arrest and Migration Suppression.

Liver cancer is the second most lethal cancer and hepatocellular carcinoma (HCC) is the primary cancer subgroup. However, the current chemotherapy agents remain ineffective and present wide side effects for advanced HCC patient. In this study, we investigated the antitumor role of ethanol extract of root of peach tree (Prunus persica (L.) Batsch and hereafter designated as TSG in short of its Chinese name), which is an important ingredient in Chinese medicine prescription, in liver cancer cell HepG2. By cell viability assay, we showed that addition of TSG in the culture medium inhibited the cell growth of HepG2 cells in a dose and time-dependent way. Cell cycle analysis indicated that TSG caused sustained M/G2 phase arrest. The expression of mitosis-related protein Cdc25c was impaired upon TSG treatment. Furthermore, wound healing assay demonstrated that TSG treatment notably suppressed the migration of HepG2 cells and the expression of extracellular matrix metalloprotease, MMP3 and MMP9. Most significantly, administration of TSG inhibited in vivo tumor growth in nude mice. Our findings suggested that TSG may serve as a source to isolate anti-HCC therapeutic ingredients.

Ginsenoside Rg1 reduces aldosterone-induced autophagy via the AMPK/mTOR pathway in NRK-52E cells.

Aldosterone is a steroid hormone secreted from the adrenal cortex, which regulates blood pressure. Higher concentrations of aldosterone can cause several diseases, including hypertension, diabetic nephropathy and chronic kidney disease. Previous reports have demonstrated that aldosterone has a pathogenic role in renal injury via reactive oxygen species (ROS), which involves the regulation of autophagy. However, whether aldosterone can induce autophagy in renal tubular cells remains to be elucidated. In the present study, elevated autophagy was observed in rat renal tubular NRK-52E cells exposed to aldosterone, which was demonstrated by the increased number of autophagosomes, conversion of LC3-I to LC3-II and the expression of Beclin-1. The enhanced autophagy was accompanied by increased production of intracellular ROS, which was reversed by N-acetylcysteine, a specific inhibitor of ROS signaling. Furthermore, treatment with ginsenoside Rg1 reduced the aldosterone-induced autophagy and production of ROS, possibly through reducing the phosphorylation of AMPK and preserving mTOR activity. These findings demonstrated that aldosterone promoted ROS generation and increased autophagy in the NRK-52E cells. Ginsenoside Rg1 effectively relieved aldosterone-induced oxidative stress and abnormal autophagy, suggesting that Rg1 may be used as a potential therapeutic drug to inhibit the renal injury, which is induced by aldosterone.