Natural compounds efficacy in complicated diabetes: A new twist impacting ferroptosis.

Ferroptosis, as a way of cell death, participates in the body's normal physiological and pathological regulation. Recent studies have shown that ferroptosis may damage glucose-stimulated islets ß Insulin secretion and programmed cell death of T2DM target organs are involved in the pathogenesis of T2DM and its complications. Targeting suppression of ferroptosis with specific inhibitors may provide new therapeutic opportunities for previously untreated T2DM and its target organs. Current studies suggest that natural bioactive compounds, which are abundantly available in drugs, foods, and medicinal plants for the treatment of T2DM and its target organs, have recently received significant attention for their various biological activities and minimal toxicity, and that many natural compounds appear to have a significant role in the regulation of ferroptosis in T2DM and its target organs. Therefore, this review summarized the potential treatment strategies of natural compounds as ferroptosis inhibitors to treat T2DM and its complications, providing potential lead compounds and natural phytochemical molecular nuclei for future drug research and development to intervene in ferroptosis in T2DM.

Effect of natural polyphenols in Chinese herbal medicine on obesity and diabetes: Interactions among gut microbiota, metabolism, and immunity.

With global prevalence, metabolic diseases, represented by obesity and type 2 diabetes mellitus (T2DM), have a huge burden on human health and medical expenses. It is estimated that obese population has doubled in recent 40 years, and population with diabetes will increase 1.5 times in next 25 years, which has inspired the pursuit of economical and effective prevention and treatment methods. Natural polyphenols are emerging as a class of natural bioactive compounds with potential beneficial effects on the alleviation of obesity and T2DM. In this review, we investigated the network interaction mechanism of "gut microbial disturbance, metabolic disorder, and immune imbalance" in both obesity and T2DM and systemically summarized their multiple targets in the treatment of obesity and T2DM, including enrichment of the beneficial gut microbiota (genera Bifidobacterium, Akkermansia, and Lactobacillus) and upregulation of the levels of gut microbiota-derived metabolites [short-chain fatty acids (SCFAs)] and bile acids (BAs). Moreover, we explored their effect on host glucolipid metabolism, the AMPK pathway, and immune modulation via the inhibition of pro-inflammatory immune cells (M1-like Mϕs, Th1, and Th17 cells); proliferation, recruitment, differentiation, and function; and related cytokines (TNF-α, IL-1ß, IL-6, IL-17, and MCP-1). We hope to provide evidence to promote the clinical application of natural polyphenols in the management of obesity and T2DM.

Paricalcitol in hemodialysis patients with secondary hyperparathyroidism and its potential benefits.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common complication in patients with end-stage renal disease and it is also common in hemodialysis patients. SHPT can increase bone fragility and calcification of blood vessels and soft tissues, which greatly increases the risk of death. AIM: To discuss the outcome, safety and other potential benefits of paricalcitol injection in hemodialysis patients with SHPT. METHODS: We recruited 40 patients who received hemodialysis at our hospital for chronic renal failure with SHPT between March and December 2019. They received paricalcitol injection for 24 wk (starting dose, 0.06-0.08 µg/kg), three times per week. They were followed up at the baseline (week 0), week 4, week 12 and week 24. The primary outcome indicator was the percentage of patients with a > 30% decrease in intact parathyroid hormone (iPTH) levels at week 24 compared with the baseline. The secondary outcome indicators included percentage decrease in iPTH levels at week 24, standard-reaching rate of iPTH (percentage of patients with iPTH down to 130-585 pg/mL), changes in serum levels of calcium (Ca), phosphate (P), Ca × P product, alkaline phosphatase (ALP), creatinine (Cre), hemoglobin (Hb), and C-reactive protein (CRP), and incidence of adverse events (AEs). RESULTS: After 24 wk of treatment, iPTH levels decreased significantly (598.88 ± 381.29 pg/mL vs 888.84 ± 376.88 pg/mL, P < 0.05). More than 30% decrease of iPTH was found in 21 of 36 (58.33%) patients. The average decrease in iPTH levels was 32.16 ± 4.33%; the standard-reaching rate of iPTH levels was 66.67% (24/36); and ALP levels decreased significantly compared with the baseline (113.72 ± 41.73 IU/L vs 133.45 ± 56.86 IU/L) (t = 2.798, P < 0.05). There were no significant differences in the serum levels of calcium, Hb, Cre and CRP compared with the baseline (P > 0.05). After 24 wk of treatment, serum P levels decreased compared with the baseline (1.91 ± 0.40 mmol/L vs 2.16 ± 0.66 mmol/L) (t = 2.830, P < 0.05). Ca × P product decreased significantly compared with the baseline (56.38 ± 13.22 mg2/dL2 vs 63.97 ± 20.30 mg2/dL2) (t = 2.717, P < 0.05). No serious adverse events occurred. CONCLUSION: Paricalcitol was a safe and effective treatment for hemodialysis patients with SHPT. It decreased serum levels of iPTH, ALP and P and maintained stability of serum Ca levels.