Ethylene glycol energetically disfavours oligomerization of pseudoisocyanine dyestuffs at crowded concentrations.

The intriguing role of the intracellular crowded environment in regulating protein aggregation remains elusive. The convolution of several factors such as the protein sequence-dependence, crowder's shape and size and diverse intermolecular interactions makes it complex to identify systematic trends. One of the ways to simplify the problem is to study a synthetic model for self-assembling proteins. In this study, we examine the aggregation behaviour of the cationic pseudoisocyanine chloride (PIC) dyestuff which is known to self-assemble and form fibril-like J-aggregates in aqueous solutions, similar to those formed by amyloid-forming proteins. Prior experimental studies have shown that polyethylene glycol impedes and Ficoll-400 promotes the self-assembly of PIC dyes. To achieve molecular insights, we examine the effect of crowding by ethylene glycol on the solvation thermodynamics of oligomerization of dyes into H-type and J-type oligomers using extensive molecular dynamics simulations. The binding free energy calculations show that the formation of J-oligomers is more favourable than that of H-oligomers in water. The stability of H- and J- tetramers and pentamers decreases in crowded solutions. The formation of oligomers is supported by the favourable change in dye-solvent interaction energy in both pure water and aqueous ethylene glycol solution although it is opposed by the reduced dye-solvent entropy. Ethylene glycol, as a molecular crowder, disfavours the H- as well as J-oligomerization via preferential binding to the dye oligomers. An unfavourable change in dye-crowder and dye-dye interaction energy on dye association makes the H-oligomer formation less favourable in crowded solution than in pure water solution. In the case of J-oligomers, however, the unfavourable change in dye-crowder interaction energy primarily contributes to making total dye-solvent energy unfavourable. The results are supported by isothermal titration calorimetry measurements where the binding of ethylene glycol to PIC molecules is found to be endothermic. The results provide an emerging view that a crowded environment can disfavour self-assembly of PIC dyes by interactions with the oligomeric states. The findings have implications in understanding the role of a crowded environment in shaping the free energy landscapes of proteins.

Identification of Potential Antitubulin Agents with Anticancer Assets from a Series of Imidazo[1,2-a]quinoxaline Derivatives: In Silico and In Vitro Approaches.

Computer-aided drug design is a powerful and promising tool for drug design and development, with a reduced cost and time. In the current study, we rationally selected a library of 34 fused imidazo[1,2-a]quinoxaline derivatives and performed virtual screening, molecular docking, and molecular mechanics for a lead identification against tubulin as an anticancer molecule. The computational analysis and pharmacophoric features were represented as 1A2; this was a potential lead against tubulin, with a maximized affinity and binding score at the colchicine-binding site of tubulin. The efficiency of this lead molecule was further identified using an in vitro assay on a tubulin enzyme and the anticancer potential was established using an MTT assay. Compound 1A2 (IC50 = 4.33-6.11 µM against MCF-7, MDA-MB-231, HCT-116, and A549 cell lines) displayed encouraging results similar to the standard drug colchicine in these in vitro studies, which further confirmed the effectiveness of CADD in new drug developments. Thus, we successfully applied the utility of in silico techniques to identify the best plausible leads from the fused azaheterocycles.

Efficacy of Cicuta virosa medicinal preparations against pentylenetetrazole-induced seizures.

Epileptic seizures are characterized by imbalanced inhibition-excitation cycle that triggers biochemical alterations responsible for jeopardized neuronal integrity. Conventional antiepileptic drugs (AEDs) have been the mainstay option for treatment and control; however, symptomatic control and potential to exacerbate the seizure condition calls for viable alternative to these chemical agents. In this context, natural product-based therapies have accrued great interest in recent years due to competent disease management potential and lower associated adversities. Cicuta virosa (CV) is one such herbal remedy that is used in traditional system of medicine against myriad of disorders including epilepsy. Homeopathic medicinal preparations (HMPs) of CV were assessed for their efficacy in pentylenetetrazole (PTZ)-induced acute and kindling models of epilepsy. CV HMPs increased the latency and reduced the duration of tonic-clonic phase in acute model while lowering the kindling score in the kindling model that signified their role in modulating GABAergic neurotransmission and potassium conductance. Kindling-induced impairment of cognition, memory, and motor coordination was ameliorated by the CV HMPs that substantiated their efficacy in imparting sustained neuronal fortification. Furthermore, biochemical evaluation showed attenuated oxidative stress load through reduced lipid peroxidation and strengthened free radical scavenging mechanism. Taken together, CV HMPs exhibited promising results in acute and kindling models and must be further assessed through molecular and epigenomic studies.

Novel nano-insulin formulation modulates cytokine secretion and remodeling to accelerate diabetic wound healing.

Little is known about insulin's wound healing capability in normal as well as diabetic conditions. We here report specific interaction of silver nanoparticles (AgNPs) with insulin by making a ~2 nm thick coat around the AgNPs and its potent wound healing efficacy. Characterization of the interaction of human insulin with silver nanoparticles showed confirmed alteration of amide-I in insulin whereas amide-II and III remained unaltered. Further, nanoparticles protein interaction kinetics showed spontaneous interaction at physiological temperature with ΔG, ΔS, Ea and Ka values -7.48, 0.076, 3.84 kcal mol-1 and 6 × 105 s-1 respectively. Insulin loaded AgNPs (IAgNPs) showed significant improvement in healing activity in vitro (HEKa cells) and in vivo (Wister Rats) in comparison with the control in both normal and diabetic conditions. The underlying mechanism was attributed to a regulation of the balance between pro (IL-6, TNFα) and anti-inflammatory cytokines (IL-10) at the wound site to promote faster wound remodeling.

Pulmonary hypertension: Molecular aspects of current therapeutic intervention and future direction.

Pulmonary hypertension (PH) is a life-threatening lung disorder with towering prevalence and risk for future has been gradually rising worldwide. Even, no specific medications are available for pulmonary hypertension; various classes of treatment based upon the origin and magnitude of hypertension are still used for the treatment of PH. Consideration of molecular or signaling modulation is the imperative approach that can offer a new notion for prevalent pharmacotherapeutic agents. Instead of concurrent targets, including endothelin receptor antagonists (ETA/ETB), phosphodiesterase 5 inhibitor (PDF-5), calcium channel blockers, anticoagulants, diuretics, and long acting prostacyclin analog, recent scientific reports revealed the numerous potential alternative therapeutic approaches that can significantly target the pathological signaling alteration associated with PH. Understanding precise molecular cascade involved in PH can be useful for designing preclinical animal experiments and human clinical trials to evaluate target specific novel therapeutic interventions for the treatment of PH. In this review, we discussed the possible molecular signaling involved in the pathogenesis of PH and detailed account of the current status of medications employed for the treatment of PH. Moreover, the newly identified potential target sites and alternative approaches for treating the PH have been discussed.

Exercise preconditioning and low dose copper nanoparticles exhibits cardioprotection through targeting GSK-3ß phosphorylation in ischemia/reperfusion induced myocardial infarction.

BACKGROUND: Drinking water from copper vessels and aerobic exercise have been the known facts for cardioprotection. Our previous report explored the significant cardioprotective potential of copper and exercise training by increasing phosphorylation of GSK-3ß and anti-oxidant potential. OBJECTIVE: Present study focuses the therapeutic potential of CuNP and exercise training through their molecular interaction with GSK-3ß, inflammatory cytokinin, oxidative stress and necrosis. METHODS: The Myocardial damage was assessed by estimating the serum nitrite/nitrate concentration, increased CKMB, LDH, cTnI level, oxidative stress, inflammatory cytokinin and structural abnormalities in I/R insulted rats. Expression of Akt/pAkt and GSK-3ß/pGSK-3ß was measured by western blotting. RESULT: Treatment with CuNP (1 mg/kg/day, p.o., 4 weeks) and exercise training (swimming, 90 min/4 weeks) either alone or in combination markedly reduced I/R induced myocardial damage by attenuating biochemical and structural alteration. A significant reduction in oxidative stress and inflammatory mediators were observed in CuNP and exercise training treatment against I/R insulted rats. Moreover, improved serum NO bioavailability was observed in CuNP and exercise treated rats. Wortmannin associated blockage of cardioprotection induced by CuNP and exercise training and up-regulation of pAkt and pGSK-3ß in I/R insulted heart confirmed the GSK-3ß phosphorylation potential of CuNP and exercise training and -associated cardioprotection. CONCLUSION: Treatment with CuNP and exercise training either alone or in combination favourably phosphorylate GSK-3ß kinase pathways and further diminish oxidative stress, inflammatory cytokines, apoptosis and increase serum bioavailability of NO in the I/R insulted rats which tends to protect myocardial damage.

Effects of Polymer Architecture and Charged Molecular Crowders on Hydrophobic Polymer Collapse.

Accounting for the crowding effects inside a living cell is crucial to obtain a comprehensive view of the biomolecular processes and designing responsive polymer-based materials for biomedical applications. These effects have long been synonymous with the entropic volume exclusion effects. The role of soft, attractive intermolecular interactions remains elusive. Here, we investigate the effects of model cationic and anionic hydrophobic molecular crowders on the collapse equilibrium of uncharged model polymers using molecular dynamics simulations. Particularly, the effect of polymer architecture is explored where a 50-bead linear polymer model (Poly-I) and a branched polymer model (Poly-II) with nonpolar side chains are examined. The collapse of Poly-I is found to be highly favorable than in Poly-II in neat water. Addition of anionic crowders strengthens hydrophobic collapse in Poly-I, whereas collapse of Poly-II is only slightly favored over that in neat water. The thermodynamic driving forces are quite distinct in water. Collapse of Poly-I is driven by the favorable polymer-solvent entropy change (due to loss of waters to bulk on collapse), whereas collapse of Poly-II is driven by the favorable polymer-solvent energy change (due to favorable intrapolymer energy). The anionic crowders support the entropic mechanism for Poly-I by acting like surfactants, redirecting water dipoles toward themselves, and preferentially adsorbing on the Poly-I surface. In the case of Poly-II, the anionic crowders are loosely bound to polymer side chains, and loss of crowders and waters to the bulk on polymer collapse reduces the entropic penalty, thereby making collapse free energy slightly more favorable than in neat water. The results indicate the discriminating behavior of anionic crowders to strengthen the hydrophobic collapse. It is related to the structuring of water molecules around the termini and the central region of the two polymers. The results address the modulation of hydrophobic hydration by weakly hydrated ionic hydrophobes at crowded concentrations.

In Silico View of Crowding: Biomolecular Processes to Nanomaterial Design.

It is widely accepted that deciphering biomolecular structure and function requires going beyond the single-molecule or single-complex paradigm. The densely packed macromolecules, cosolutes, and metabolites in the living cell impose crowding effects on the biomolecular structure and dynamics that need to be accounted for. Molecular simulations have proven to be a powerful tool to advance the current molecular-level understanding of such a highly concentrated, complex milieu. This Mini-Review focuses on summarizing the understanding achieved so far for the effects of crowding on biomolecular processes using computational methods, along with highlighting a new direction in employing crowding as a tool for tunable nanomaterial design. The two schools of thought that form the pillars of the current understanding of crowding effects are discussed. The investigation of crowded solutions using physics-based models that encompass different time and length scales to mimic the intracellular environment are described. The limitations and challenges faced by the current models and simulation methods are addressed, highlighting the gaps to be filled for better agreement with experiments. Crowding can also act as an effective tool to modulate the structure-property-function relationships of nanomaterials, leading to the development of novel functional materials. A few recent studies, mostly experimental, have been summarized in this direction. The Mini-Review concludes with an outlook for future developments in this field in order to enable accurate mimicking of the intracellular environment using simulations and to bridge the gap between biological processes and nanomaterial design.

Antidiabetic Evaluation of Kigelia pinnata Root Bark Extract in Streptozotocin-Induced Type-2 Diabetes Model of Rats.

Diabetes mellitus (DM) is the most common endocrine disorder characterized by increased blood glucose levels resulting from defective insulin secretion, resistance to insulin action, or both. DM is often associated with severe complications, and there is an increasing appreciation that cognitive function declines in DM. The aim of this research work was to evaluate Kigelia pinnata root bark extract in Streptozotocin (STZ)-induced type-2 diabetes. Experimental diabetes was induced by a single administration of STZ (60 mg/kg, intraperitoneal [i.p.]), immediately after the STZ administration, and all animals were fed with normal food and water. Nicotinamide was administered (120 mg/kg, i.p.) 15 min before STZ. The development of hyperglycemia was confirmed by the elevated blood glucose levels determined at fixed intervals, which was confirmed by measuring fasting blood glucose levels in rats' blood taken from the tail vein. Supplementation with ethanolic extract of K. pinnata root bark (EEKP) significantly reduced the elevated blood glucose in STZ-induced hyperglycemia in rats. EEKP significantly restored the biochemical and antioxidant defense system. On the final day of the protocol, the extract also reduced inflammatory cytokines in the blood serum.

Incredible Combination of Lifestyle Modification and Herbal Remedies for Polycystic Ovarian Syndrome Management.

A relatively frequent endocrine-metabolic illness called polycystic ovarian syndrome (PCOS) is characterized by polycystic ovaries, persistent anovulation, and hyperandrogenism, which cause symptoms such as irregular menstruation, infertility, and hirsutism. PCOS is linked to obesity, insulin resistance, and increased amounts of androgens, or male hormones. The sedentary lifestyle, dietary fluctuations, inactivity, and stress are other contributing variables. According to estimates from India in 2021, around 22.5% of women, or one in five Indian women, suffer from PCOS. Evidence-based medical care for PCOS places a strong focus on a multidisciplinary approach, as standard pharmacological treatment frequently targets a single symptom, may be contraindicated, has adverse effects, and is ineffective in certain circumstances. However, long-term treatments have drawbacks and are likely to be ineffective, making complementary and alternative therapies a worthwhile choice. Yoga science is a thorough treatment plan for a healthy body and mind that may eradicate PCOS's primary causes, stress and obesity. Some common herbal remedies, including Foeniculum vulgare, Tinospora cordifolia, Asparagus racemosus, Ocimum tenuiflorum, Areca catechu, and Lepidium meyenii, have been highly regarded sources that have the benefits of lowering PCOS as well as having hypoglycemic and antiobesity effects. In light of existing literature, women with PCOS experienced symptomatic relief, improvement in hormonal balance, and the quality of life by utilizing yoga practices as well as herbal remedies. In conclusion, combining lifestyle modifications with herbal remedies can be used in the management of PCOS as a holistic approach. Therefore, this review opens a new window for researchers all across the world to validate such findings.

Single and repeated dose (28 days) intravenous toxicity assessment of bartogenic acid (an active pentacyclic triterpenoid) isolated from Barringtonia racemosa (L.) fruits in mice.

Bartogenic acid (BA), an active pentacyclic triterpenoid, has been reported for anti-diabetic, anti-inflammatory, anti-arthritic, anti-cancer, and anti-tumor activity. However, toxicity profiling of BA has not been reported till date. Hence, this study is designed to evaluate the single dose (12.5, 25, 50 and 100 mg/kg) and repeated dose (1.5, 6, and 24 mg/kg) intravenous toxicity of BA in BALB/c mice. Control group received vehicle. In single dose toxicity study, two mortalities were observed at 100 mg/kg of BA whereas lower doses were well tolerated. In repeated dose toxicity study, no mortality was observed. 1.5 mg/kg of BA was well tolerated in mice of both sexes. At 6 mg/kg of BA, female mice showed significant reduction in the body weight as compared to the control group however no significant change was observed in male mice. 24 mg/kg of BA showed significant reduction in the body weight in mice of both sexes. Further, these mice showed significant change in the relative organ weight. However, no toxicologically relevant changes were observed in hematology, biochemistry, and histopathology. Based on the findings, No-Observed-Adverse-Effect-Level (NOAEL) for BA were found to be<24 mg/kg for male mice and<6 mg/kg for female mice.

Effect of pantoprazole on I-R-induced myocardial injury in diabetic rats targeting inflammatory cytokine release and oxidative stress.

OBJECTIVES: To evaluate the pleiotropic potential and underlying mechanism of pantoprazole (PPZ) (common Proton Pump Inhibitors, PPIs) in type 2 diabetes mellitus (T2DM) -associated ischemia/reperfusion (I-R)-induced myocardial infarction which is still uncharted. Whereas some other PPIs have demonstrated their anti-diabetic, antioxidant, and anti-inflammatory potential. MATERIALS AND METHODS: We evaluated the potential of coinciding treatment of PPZ (4 mg/kg/po/day for 8 weeks) in Wistar albino rats against STZ (50 mg/kg/IP) induced T2DM model and I-R provoked cardiac infarction model in diabetic and non-diabetic condition. RESULTS: PPZ significantly inhibited the perturbed deviations in blood glucose concentration, HbA1c, C-peptide, plasma insulin, and ameliorated the lipid profile (dyslipidemia). PPZ protected myocardial tissue against lipid peroxidation by restoring the levels of serum TBARS and reduced NBT. The significant protective effects of PPZ were evident by ameliorating CKMB, LDH, cTnI, and myocardial oxidative stress in PPZ treated animals. Additionally, PPZ prominently reduced various proinflammatory cytokines release including TGF-ß1, TNF-α, and IL-6. PPZ upsurges the bioavailability of nitrite/nitrate concentration which may pacify the impact of myocardial infarction in diabetic I-R injury. CONCLUSION: The consequences indicate that PPZ possesses a potent protective effect against diabetic I-R-induced myocardial infarction via suppressing oxidative stress, inflammation, and dyslipidemia-associated tissue damage.

Cognition and memory impairment attenuation via reduction of oxidative stress in acute and chronic mice models of epilepsy using antiepileptogenic Nux vomica.

Ethnopharmacological relevance Processed Nux vomica seed extracts and homeopathic medicinal preparations (HMPs) are widely used in traditional Indian and Chinese medicine for respiratory, digestive, neurological and behavioral disorders. Antioxidant property of Nux vomica is well known and recent investigation has highlighted the anticonvulsant potential of its homeopathic formulation. AIM OF THE STUDY: To explore the anticonvulsant and antiepileptogenic potential of Nux vomica HMPs (6CH, 12CH and 30CH potency) in pentylenetetrazole (PTZ) induced acute and chronic experimental seizure models in mice and investigate their effects on cognition, memory, motor activity and oxidative stress markers in kindled animals. MATERIALS AND METHODS: Acute seizures were induced in the animals through 70 mg/kg (i.p.) administration of PTZ followed by the evaluation of latency and duration of Generalized tonic-clonic seizures (GTCS). Subconvulsive PTZ doses (35 mg/kg, i.p.) induced kindling in 29 days, which was followed by assessment of cognition, memory and motor impairment through validated behavioral techniques. The status of oxidative stress was estimated through measurement of MDA, GSH and SOD. RESULTS: HMPs delayed the latency and reduced the duration of GTCS in acute model signifying possible regulation of GABAergic neurotransmission. Kindling was significantly hindered by the HMPs that justified the ameliorated cognition, memory and motor activity impairment. The HMPs attenuated lipid peroxidation by reducing MDA level and strengthened the antioxidant mechanism by enhancing the GSH and SOD levels in the kindled animals. CONCLUSIONS: Nux vomica HMPs showed anticonvulsant and antiepileptogenic potency in acute and chronic models of epilepsy. The test drugs attenuated behavioral impairment and reduced the oxidative stress against PTZ induced kindling owing to which they can be further explored for their cellular and molecular mechanism(s).

Tumor-suppressing effect of bartogenic acid in ovarian (SKOV-3) xenograft mouse model.

Bartogenic acid (BA), a natural pentacyclic triterpenoid, proved to have chemomodulatory, anticancer, antidiabetic, anti-arthritic, and anti-inflammatory activity. Based on structure-activity relationship (SAR) approaches, BA has close structural resemblance to oleanolic acid and ursolic acid. These two pentacyclic triterpenoids are well accepted with respect to their therapeutic value in various ailments including anti-cancer activity. The aim of this study is to evaluate the efficacy of BA as a possible antitumor agent, along with its safety in SKOV-3 ovarian cancer. In vitro cytotoxicity of BA and paclitaxel on human ovarian cancer cells (SKOV-3) was assessed using MTT assay. Antitumor potential of BA alone, standard anticancer drug (paclitaxel) alone, and BA in combination with paclitaxel were evaluated in SKOV-3 xenografted SCID mice. Immunohistochemical analysis of NF-κB was performed and analyzed in SKOV-3 tumors. BA alone and BA in combination with paclitaxel significantly inhibited the tumor growth. IC50 of BA was found to be 15.72 µM. Similarly, paclitaxel showed significant antitumor effect with IC50 of 3.234 µM. Treatments of paclitaxel, BA, and combination of BA with paclitaxel were well tolerated during treatment period. Immunohistochemical analysis of NF-κB in SKOV-3 tumors treated with BA in combination with paclitaxel revealed antitumor effect in terms of inhibition of NF-κB. Our results suggested that BA exhibits promising antitumor effect in the restriction of SKOV-3 cells and tumors with considerable safety.

SIRT1 Promotes Neuronal Fortification in Neurodegenerative Diseases through Attenuation of Pathological Hallmarks and Enhancement of Cellular Lifespan.

Neurodegeneration is a complex neurological phenomenon characterized by disturbed coherence in neuronal efflux. Progressive neuronal loss and brain damage due to various age-related pathological hallmarks perturb the behavioral balance and quality of life. Sirtuins have been widely investigated for their neuroprotective role, with SIRT1 being the most contemplated member of the family. SIRT1 exhibits significant capabilities to enhance neurogenesis and cellular lifespan by regulating various pathways, which makes it an exciting therapeutic target to inhibit neurodegenerative disease progression. SIRT1 mediated neuronal fortification involves modulation of molecular co-factors and biochemical pathways responsible for the induction and sustenance of pro-inflammatory and pro-oxidative environment in the cellular milieu. In this review, we present the major role played by SIRT1 in maintaining cellular strength through the regulation of genomic stability, neuronal growth, energy metabolism, oxidative stress, inhibiting mechanisms and anti-inflammatory responses. The therapeutic significance of SIRT1 has been put into perspective through a comprehensive discussion about its ameliorating potential against neurodegenerative stimuli in a variety of diseases that characteristically impair cognition, memory and motor coordination. This review enhances the acquaintance concerned with the neuroprotective potential of SIRT1 and thus promotes the development of novel SIRT1 regulating therapeutic agents and strategies.

Dose and time-dependent toxicological impact of pantoprazole on vascular endothelium and renal tissue.

Proton pump inhibitors (PPIs) have wide pleiotropic action in addition to their therapeutic potential in gastroesophageal reflux diseases. Conversely, recent reports revealed a significant incidence of toxic events of PPIs including nephritis, osteoporosis, and cardiac damage. Thus, the study was designed to reconcile the deceptive contraindications. The present investigation targeted to reveal the toxic impact of sub-acute and sub-chronic administration of pantoprazole (PPZ) with different concentrations (low dose 4 mg/kg, medium-dose 8 mg/kg and high dose 16 mg/kg once a day) on normal vascular endothelium and renal tissue of rats. Vascular endothelial dysfunction (VED) was estimated by the contractility of an isolated aortic ring, nitrite/nitrate concentration, oxidative stress, and integrity of the endothelium layer. Moreover, the renal abnormalities were further confirmed by an increased level of serum creatinine, blood urea nitrogen (BUN), the incidence of microproteinuria, and structural alteration. Sub-acute administration of PPZ treatment did not produce any toxicological impact on endothelium and renal tissue. Whereas, sub-chronic administration of PPZ treatment causes moderate VED and renal dysfunction in a dose-dependent manner. Sub-chronic treatment of PPZ also influences the mitigation of NO and elevation of oxidative stress. Collecting all the evidence, it concludes that decreased nitric oxide availability and increased levels of oxidative stress may be a possible underlying mechanism of causing VED and renal abnormalities from high-dose PPZ treatment.

Perspective, perceptions, and promulgation of biosimilars: A questionnaire-based study to assess and understand the current challenges of biosimilars to the potential and intended users.

INTRODUCTION: Biosimiliar, a copy of reference biological product, is making a buzz across the globe for its upper edge therapeutic usage. According to the market research report published by P&S Intelligence, biosimilars market is expected to generate $26.7 billion revenue by 2024, advancing at a CAGR of 29.6% during the forecast period. The first biosimilar to medicine Omnitrope, was approved in Europe by EMA (European Medicines Agency) in year 2006. Till date countries like US, China, Japan, India and many more have generated regulatory guidelines for biosimilars. AIM: Current study addresses the issues and challenges faced by Industry and regulators with their potential solutions and recommendations. MATERIALS AND METHODS: The questionnaire having 21 important questions/comments was given to participants after explaining the purpose of the study. The response in terms of responders V/s non-responders, agree V/s disagree, yes V/s no was recorded and analyzed by descriptive statistics. RESULTS AND DISCUSSION: The study shows the limitation regarding the qualified personnel involved in biosimilars, as approx. 91% people believe that there is lack of expertise in this field. The same can be achieved through government initiatives for bridge courses which is also strongly felt by the major (83.6%) stakeholders participated in the study.

Terror of 10 MB, a cross-sectional study investigates the regulation to the prospective of medical device.

An instrument, apparatus, implement, machine, implant, in vitro reagent, a component part or accessory which Intended for use in diagnosis of disease or other condition, or in the cure, mitigation and treatment or prevention of disease is called medical devices. Medical devices under new rule classified as Class A (low risk), Class B (low moderate risk), Class C (moderate high risk), and Class D (high risk) commemorating the notification of January 31, 2017 of Ministry of Health and Family Welfare which is conformity with Global Harmonisation Task Force framework. As per make in India program, the industry of medical devices is USD 5.2 billion and is contributing 4%-5% to the USD 96.7 billion Indian health-care industry. A total of 750-800 medical device manufacturers in India, an average investment of Rs 170-200 million and an average turnover of Rs 450-500 million. An online licensing portal of the Central Drugs Standard Control Organization (CDSCO) called "Sugam portal" has been launched on November 14, 2015, to file application and grant permission of registration exclusively for Medical Device CDSCO MD Online portal. By making the document submission easier, there are lot of challenges also present in "Sugam-online Portal." One of the main challenges in Sugam Portal is that there is no provision to upload files greater than 10MB file size. The current study addresses the issues and challenges faced by medical device industry and regulators with their potential solutions and recommendations.

Acceleration of Wound Healing in Diabetic Rats through Poly Dimethylaminoethyl Acrylate-Hyaluronic Acid Polymeric Hydrogel Impregnated with a Didymocarpus pedicellatus Plant Extract.

Wound is the major health problem associated with skin damages and arises because of various types of topical injuries. Furthermore, wounds in patients with diabetes take a relatively long time to heal. Currently, herbal medicines have been extensively used for wound care and management. Here, we engineered polymeric hybrid hydrogel of dimethylaminoethyl acrylate and hyaluronic acid (pDMAEMA-HA), which was impregnated with a herbal extract of Didymocarpus pedicellatus. The developed polymeric hybrid hydrogel system can be used for effective therapy of incurable wounds. Therefore, the development of D. pedicellatus-impregnated pDMAEMA-HA (pDPi-DMAEMA-HA) hybrid hydrogel was accomplished by the synthesis of pDMAEMA-HA hydrogel via the optimization of various reaction parameters followed by impregnation of herbal drugs D. pedicellatus. The developed hydrogel composite was well characterized via various techniques, and swelling kinetics was performed to analyze the water uptake property. The swelling ratio was found to be 1600% in both types of hydrogels. To evaluate the wound healing of these polymeric hydrogels, the Wistar rats full-thickness excision wound model was utilized. The healing strength of hydrogels was determined using measurement of wound contraction and histopathological study. The results of wound healing by these polymeric hydrogels revealed that animals treated with the pDPi-DMAEMA-HA hybrid hydrogel group were found to have a higher level of wound closure as compared to marketed formulation as well as polymeric hybrid hydrogel. The histopathologic examinations implied that pDPi-DMAEMA-HA hybrid hydrogel and polymeric hybrid hydrogel-treated groups exhibited enhanced cutaneous wound repair as well as high level of cellular repair and maintenance compared to the standard group because of hyaluronic acid roles in various stages of wound repair.

Polymeric worm-like nanomicellar system for accelerated wound healing.

Self-assembly is an unparalleled step in designing macromolecular analogs of nature's simple amphiphiles. Tailoring hydrogel systems - a material with ample potential for wound healing applications - to simultaneously alleviate infection and prompt wound closure is vastly appealing. The poly (DEAEMA-co-AAc) (PDEA) is examined with a cutaneous excisional wound model alterations in wound size, and histological assessments revealed a higher wound healing rate, including dermis proliferation, re-epithelialization, reduced scar formation, and anti-inflammatory properties. Moreover, a mechanism for the formation of spherical and worm-like micelles (WLMs) is delineated using a suite of characterizations. The excellent porosity and ability to absorb exudates impart the PDEA with reliable wound healing. Altogether, this system demonstrates exceptional promise as an infection-mitigating, cell-stimulating, homeostasis-maintaining dressing for accelerated wound healing. The aim and objective of this study is to understand the mechanism of self-assembly in synthesized WLMs from PDEA and their application in wound healing.