A minor metabolite from Curcuma longa effective against metabolic syndrome: results from a randomized, double-blind, placebo-controlled clinical study.

Metabolic syndrome (MetS) is characterized by the presence of at least three interrelated risk factors, including central obesity, hypertension, elevated serum triglycerides, low serum high-density lipoproteins, and insulin resistance. Abdominal obesity is considered a predominant risk factor. Lifestyle changes with medications to lower cholesterol, blood sugar, and hypertension are the general treatment approaches. Functional foods and bioactive food ingredients represent versatile tools for addressing different aspects of MetS. In a randomized placebo-controlled clinical study, we evaluated the effect of Calebin A, a minor bioactive phytochemical from Curcuma longa, on metabolic syndrome in obese adults (N = 100), and 94 individuals completed the study (N = 47 in both groups). They were subjected to Calebin A supplementation for 90 days, which resulted in a statistically significant reduction in their body weight, waist circumference, body mass index, low-density lipoprotein-cholesterol, and triglyceride levels compared to those with the placebo. A small but significant increase in high-density lipoprotein-cholesterol levels was also observed in these individuals. Furthermore, Calebin A showed a positive effect on adipokines by reducing circulating leptin levels. Finally, C-reactive protein levels were significantly reduced in Calebin A-supplemented individuals, suggesting a beneficial impact on managing MetS-induced inflammation. Blood glucose levels, insulin resistance, and blood pressure levels were not affected by Calebin A. In conclusion, Calebin A may be an effective supplement for managing abdominal obesity, dyslipidemia, and systemic inflammation in individuals with metabolic syndrome. This study was prospectively registered on the Clinical Trial Registry of India (CTRI) with the registration number CTRI/2021/09/036495. https://ctri.nic.in/Clinicaltrials/advancesearchmain.php.

Desidustat in Anemia due to Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-D).

BACKGROUND: A phase 3 study to assess the efficacy and safety of the desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, against the epoetin alfa for the treatment of anemia in patients with chronic kidney disease (CKD) with dialysis dependency. METHODS: DREAM-D was a phase 3, multicenter, open-label, randomized, active-controlled clinical study conducted across 38 centers in India. A total of 392 patients with clinical diagnosis of anemia due to CKD with dialysis need (Erythrocyte Stimulating Agent [ESA] naïve or prior ESA users) and with baseline hemoglobin levels of 8.0-11.0 g/dL (inclusive) were randomized in a 1:1 ratio to receive either desidustat oral tablets (thrice a week) or epoetin alfa subcutaneous injection for 24 weeks to maintain a hemoglobin level of 10-12 g/dL. The primary endpoint was to assess the change in the hemoglobin level between the desidustat and the epoetin alfa groups from the baseline to evaluation period week 16-24. The key secondary efficacy endpoint was the number of patients with hemoglobin response. RESULTS: The least square mean (standard error) change in hemoglobin from the baseline to week 16-24 was 0.95 (0.09) g/dL in the desidustat group and 0.80 (0.09) g/dL in the epoetin alfa group (difference: 0.14 [0.14] g/dL; 95% confidence interval: -0.1304, 0.4202), which met the prespecified noninferiority margin. The number of hemoglobin responders was significantly higher in the desidustat group (106 [59.22%]) when compared to the epoetin alfa group (89 [48.37%]) (p = 0.0382). The safety profile of the desidustat oral tablet was comparable with the epoetin alfa injection. There were no new risks or no increased risks seen with the use of desidustat compared to epoetin alfa. CONCLUSION: In this study, desidustat was found to be noninferior to epoetin in the treatment of anemia in CKD patients on dialysis and it was well-tolerated. Clinical Trial Registry Identifier: CTRI/2019/12/022312 (India).

PAP90, a novel rice protein plays a critical role in regulation of D1 protein stability of PSII.

Introduction: Photosystem II (PSII) protein complex plays an essential role in the entire photosynthesis process. Various known and unknown protein factors are involved in the dynamics of the PSII complex that need to be characterized in crop plants for enhancing photosynthesis efficiency and productivity. Objectives: The experiments were conducted to decipher the regulatory proteins involved in PSII dynamics of rice crop. Methods: A novel rice regulatory protein PAP90 (PSII auxiliary protein ~90 kDa) was characterized by generating a loss-of-function mutant pap90. The mutation was characterized at molecular level followed by various experiments to analyze the morphological, physiological and biochemical processes of mutant under control and abiotic stresses. Results: The pap90 mutant showed reduced photosynthesis due to D1 protein instability that subsequently causes inadequate accumulation of thylakoid membrane complexes, especially PSII and decreases PSII functional efficiency. Expression of OsFtsH family genes and proteins were induced in the mutant, which are known to play a key role in D1 protein degradation and turnover. The reduced D1 protein accumulation in the mutant increased the production of reactive oxygen species (ROS). The accumulation of ROS along with the increased activity of antioxidant enzymes and induced expression of stress-associated genes and proteins in pap90 mutant contributed to its water-limited stress tolerance ability. Conclusion: We propose that PAP90 is a key auxiliary protein that interacts with D1 protein and maintains its stability, thereby promoting subsequent assembly of the PSII and associated membrane complexes.