Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival.

It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME.

A Brief Discussion of Multi-Component Organic Solids: Key Emphasis on Co-Crystallization

Co-crystallization (CCs) is a less studied phenomenon related to its applicability and reliability as it is directly related to the generation of newer multicomponent solids like co-crystals (CS), eutectic, salts or solid solutions etc. having improved physicochemical properties compared to their pure components. Further, the design and structural aspects of these multicomponent systems remain hindered compared to other techniques such as nanotechnology or solid dispersion. CC is a newer technique to modify the physicochemical as well as pharmaceutical characteristics of various drugs having issues like solubility, stability, etc. without altering or hindering their pharmacological activities. For drug delivery purpose, CC process has numerous advantages over nanotechnology and solid dispersion drug delivery techniques. CCs can modify the physicochemical properties of active pharmaceutical ingredients (API) have issues like sensitivity toward environmental hazards like temperature, moisture, or photostability issues. The availability of large numbers of conformers makes this technique favorable for the researchers in designing CS of newer and older. Although, solid dispersion and nanotechnology techniques are being utilized to a larger extent still there are some drawbacks of these techniques like stability, toxicological factors and protection from environmental factors need to be considered, while the CCs process drastically modifies the various pharmaceutical parameters without altering the pharmacological properties of API's. Salts, design of CS, their methods of preparation, and their application in various fields with special emphasis on their applicability in the pharmaceutical industry.

Role of Bioactive Phytoconstituents as Modulators of Hepatic Carbohydrates Metabolising Enzymes: A Target Specific Approach to Treat Diabetes Mellitus.

Diabetes mellitus is the most prevalent malady, becoming a leading public health concern around the world. It is a chronic endocrine metabolic disturbance that is accompanied by the commencement of a sequence of complications. The liver primarily serves as the body's glucose or fuel reserve and also maintains standard blood sugar concentration. Hepatic gluconeogenesis, glycolysis and glycogenesis are the key contributors to fasting or post-prandial hyperglycaemia in type 2 diabetes mellitus subjects. So, regulating these channels could be a viable approach for mitigating hyperglycaemia in type 2 diabetes mellitus. Few potential synthetic drugs that precisely target hepatic glucose-producing metabolic pathways are presently available, but they have some serious negative effects like hypoglycaemia, hepatosteatosis and lactic acidosis. Therefore, scientists have veered to herbal products because of their edible nature, costeffectiveness and fewer side effects. Natural products and their isolated phytochemicals are progressively being employed to manage hyperglycaemia by modulating the enzyme's activity and regulating transcription factors concerned with hepatic glucose synthesis. We reviewed the potential effects of isolated bioactive phytochemicals on interesting targets that affect hepatic glucose homeostasis in diabetes. This study illustrates the benefit and feasibility of developing liver-specific drugs through secondary metabolites to restore hyperglycaemia.

Review on people's trust on home use medical devices during Covid-19 pandemic in India.

With the rapid development of the medical device against COVID-19 is an excellent achievement. There are numerous obstacles effectively facing the worldwide population, from manufacture to distribution, deployment and, acceptance. Many manufacturers have entered the market rivalry as people's knowledge and demand for home-use medical equipment has increased. India represents a compelling market opportunity for global medical device manufacturers. Substantial growth for the Indian medical device industry is expected to be driven by the current low per-person spending rate for medical devices. The growth of the medical devices industry in India raises competition law issues (anti-trust) and therefore maintaining public trust in home-use medical devices during COVID-19 will be as essential. The review article aims to create awareness among people about commonly used medical devices during the COVID-19 pandemic and to survey people's trust in home usable medical devices in India. In a worldwide pandemic, manufacturers of medical devices face insufficient storage and the impossibility of meeting the requirements of the health centre. The sale of some of the most significant medical devices has increased, making it more difficult for the medical device industry to satisfy demand with high-quality goods since the quality of COVID-19 items plays a vital part in the present scenario. Despite the difficulty in providing enough medical equipment during a pandemic, they are striving to adapt to the circumstance. After recognizing the need to promote awareness and grasp the selling, and production, handling of medical instruments during COVID-19 at home was conducted. In addition, medical equipment manufacturers and distributors look at this scenario as an opportunity to profit more. This review article would enable researchers during COVID-19 to build more knowledge and widespread trust in medical technologies respectively.

Ethnopharmacological perspectives of glucokinase activators in the treatment of diabetes mellitus.

Traditional medicinal plants have wide-reaching utilisation in the treatment of diabetes especially in developing countries where medical resources are meagre. Traditionally used anti-diabetic plants act by numerous mechanisms, however, only a few of them act through activation of the glucokinase enzyme. Glucokinase is a key regulatory enzyme in glucose metabolism thereby controls glucose homeostasis and insulin secretion. The present review significantly analyses the knowledge about various plant-based glucokinase activators including numerous phytochemicals which modulate the activity and gene expression of glucokinase and would provide data support and perspective regarding future research in the discovery and development of different plant-derived glucokinase activators.

Medicinal plants with potential anti-arthritic activity.

ETHNO PHARMACOLOGICAL RELEVANCE: Traditional medicinal plants are practiced worldwide for treatment of arthritis especially in developing countries where resources are meager. This review presents the plants profiles inhabiting throughout the world regarding their traditional usage by various tribes/ethnic groups for treatment of arthritis. MATERIALS AND METHODS: Bibliographic investigation was carried out by analyzing classical text books and peer reviewed papers, consulting worldwide accepted scientific databases from the last six decades. Plants/their parts/extracts/polyherbal formulations, toxicity studies for arthritis have been included in the review article. The profiles presented also include information about the scientific name, family, dose, methodology along with mechanism of action and toxicity profile. Research status of 20 potential plant species has been discussed. Further, geographical distribution of research, plants distribution according to families has been given in graphical form. RESULTS: 485 plant species belonging to 100 families, traditionally used in arthritis are used. Among 100 plant families, malvaceae constitute 16, leguminasae 7, fabaceae 13, euphorbiaceae 7, compositae 20, araceae 7, solanaceae 12, liliaceae 9, apocynaceae, lauraceae, and rubiaceae 10, and remaining in lesser proportion. It was observed in our study that majority of researches are carried mainly in developing countries like India, China, Korea and Nigeria. CONCLUSION: This review clearly indicates that list of medicinal plants presented in this review might be useful to researchers as well as practioners. This review can be useful for preliminary screening of potential anti-arthritis plants. Further toxicity profile given in the review can be useful for the researchers for finding the safe dose.

Investigation of antiarthritic potential of Plumeria alba L. leaves in acute and chronic models of arthritis.

AIM: The present investigation was designed to evaluate antiarthritic potential of fractions of hydroalcoholic extract from leaves of P. alba. MATERIALS AND METHODS: Plumeria alba L. leaves were extracted with hydroalcohol (30 : 70) to obtain hydroalcoholic extract of P. alba. This extract was further fractionated with solvents ethyl acetate and n-butanol to obtain EAPA and BPA, respectively. These fractions were tested against formaldehyde and Freund's complete adjuvant (FCA) induced arthritis. Arthritis assessment, paw volume, body weight, motor incoordination, and nociceptive threshold were measured. On day 21, the animals were sacrificed and histopathology was done. RESULTS: The 100 and 200 mg/kg doses of EAPA and BPA caused a significant (P ≤ 0.05-0.01) reduction in paw swelling in both models. Erythrocyte sedimentation rate (ESR) and spleen weight decreased significantly (P < 0.01) in arthritic rats treated with extracts. There was significant (P < 0.05) improvement in thymus weight in EAPA treated rats whereas significant (P < 0.01) improvement was also seen in haemoglobin level (Hb) in diclofenac treated group. Motor incoordination and nociceptive threshold were also significantly (P ≤ 0.05-0.01) improved. CONCLUSION: The present study suggests that Plumeria alba L. has protective activity against arthritis and supports the traditional use of P. alba for rheumatism and other inflammatory diseases.

Gastric antisecretory and cytoprotective effects of hydroalcoholic extracts of Plumeria alba Linn. leaves in rats.

OBJECTIVE: This study was conducted to evaluate the antiulcerogenic property of hydroalcoholic extract obtained from the leaves of Plumeria alba Linn. METHODS: Antiulcer assays were performed using the protocols of ulcer induced by non-steroidal anti-inflammatory drugs, ethanol and pylorus ligation. The hydroalcoholic extract (HAPA), and various fractions of HAPA like, n-hexane extract (HPA), ethyl acetate extract (EAPA) and n-butanol extract (BPA) were administered at doses of 200 and 400 mg/kg for HAPA and 100 and 200 mg/kg for fractions of extracts. Parameters of gastric secretion (volume, pH, total protein, and free and total acidity) were determined by the pylorus ligation model. Parameters like aspartate aminotransferase and alanine aminotransferase were also determined in ethanol-induced ulcer model. To determine the mechanism of action, role of nitric oxide was also evaluated. RESULTS: EAPA and BPA (100 and 200 mg/kg, p.o.) showed gastric ulcer-healing effect in indomethacin-induced ulcer model, while HAPA (200 mg/kg) and HPA showed no significant antiulcer effect. Both EAPA and BPA showed gastric cytoprotective effect in ethanol-induced gastric ulcer and inhibited gastric secretion in pylorus-ligated rats. CONCLUSION: The results of the present study show that some hydroalcoholic extract of Plumeria alba L. displays antiulcer activity, as demonstrated by the significant inhibition of ulcer formation induced by different models, which is consistent with the literature report in folk medicine.