Effect of 1,25 dihydroxy vitamin D3 supplementation on pain relief in early rheumatoid arthritis.

BACKGROUND: To assess effect of 1,25 dihydroxy vitamin D3 supplementation on pain relief in early rheumatoid arthritis (RA). MATERIALS AND METHODS: An open-labeled randomized trial was conducted comparing 60,000 IU 1,25 dihydroxy vitamin D3 + calcium (1000 mg/day) combination [Group A] versus calcium (1000 mg/day) only [Group B], as supplement to existing treatment regimen in early RA. Primary outcome included (i) minimum time required for onset of pain relief (Tm) assessed through patients' visual analog scale (VAS); (ii) % change in VAS score from onset of pain relief to end of 8 weeks. Secondary outcome included change in disease activity score (DAS-28). RESULTS: At the end of 8-weeks, Group A reported 50% higher median pain relief scores (80% vs. 30%; P < 0.001) and DAS-28 scores (2.9 ± 0.6 vs. 3.1 ± 0.4; P = 0.012) compared to Group B; however, Tm remained comparable (19 ± 2 vs. 20 ± 2 days; P = 0.419). Occurrence of hypovitaminosis-D was lower (23.3%) compared to Indian prevalence rates and was a risk factor for developing active disease (Odds Ratio (OR) = 7.52 [95% Confidence Interval (CI) 2.67-21.16], P < 0.0001). Vitamin D deficiency was significantly (P < 0.001) more common in female gender, active disease, and shorter mean disease duration. Vitamin D levels were inversely correlated to disease activity as assessed by DAS-28 (r = -0.604; P < 0.001). CONCLUSIONS: Vitamin-D deficiency is a risk factor for developing active disease in RA. Weekly supplementation of 60,000 IU of 1,25 dihydroxy vitamin D3 in early RA results in greater pain relief. The number needed to treat for this additional pain relief was 2. IDENTIFIER: CTRI/2018/01/011532 (www.ctri.nic.in).

Andrographolide binds to ATP-binding pocket of VEGFR2 to impede VEGFA-mediated tumor-angiogenesis.

Vasculogenesis and angiogenesis are process of formation of blood vessels. Blood vessels are evolved to distribute nutrients and oxygen to distant organs. These vessels are crucial for growth and repair of wounded tissue. During tumor condition there occurs imbalance in the growth of blood vessels which leads to neo-angiogenesis. Neo-angiogenesis is major perpetrator behind the establishment of tumor. Tumor cells secrete pro-angiogenic factor VEGFA which binds to VEGFR2 present over surface of endothelial cells and triggers formation of new blood vessels. To inhibit tumor-angiogenesis, a physiologically-safe small molecule inhibitor was screened which can potentially interact with kinase domain of VEGFR2 and inhibit its activity. Molecular-docking module and biochemical analysis identified andrographolide as one of the best docking molecules that binds to ATP-binding pocket of VEGFR2 and inhibits its kinase activity. Thus, for a more radical approach towards safe VEGFR2 inhibitor, andrographolide was repurposed to inhibit tumor-angiogenesis and reduce tumor burden.

New insights into therapeutic activity and anticancer properties of curcumin.

Natural compounds obtained from plants are capable of garnering considerable attention from the scientific community, primarily due to their ability to check and prevent the onset and progress of cancer. These natural compounds are primarily used due to their nontoxic nature and the fewer side effects they cause compared to chemotherapeutic drugs. Furthermore, such natural products perform even better when given as an adjuvant along with traditional chemotherapeutic drugs, thereby enhancing the potential of chemotherapeutics and simultaneously reducing their undesired side effects. Curcumin, a naturally occurring polyphenol compound found in the plant Curcuma longa, is used as an Indian spice. It regulates not only the various pathways of the immune system, cell cycle checkpoints, apoptosis, and antioxidant response but also numerous intracellular targets, including pathways and protein molecules controlling tumor progression. Many recent studies conducted by major research groups around the globe suggest the use of curcumin as a chemopreventive adjuvant molecule to maximize and minimize the desired effects and side effects of chemotherapeutic drugs. However, low bioavailability of a curcumin molecule is the primary challenge encountered in adjuvant therapy. This review explores different therapeutic interactions of curcumin along with its targeted pathways and molecules that are involved in the regulation of onset and progression of different types of cancers, cancer treatment, and the strategies to overcome bioavailability issues and new targets of curcumin in the ever-growing field of cancer.