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Vesicular systems endow large opportunities for the transdermal delivery of therapeutics. The present study was designed to investigate the potential of a novel class of vesicular system ‘proniosome’ as a carrier for transdermal delivery of bromocriptine (BCT). Proniosome formulations were prepared by the coacervation-phase separation method and the influence of factors like surfactant type and its amount, lipid concentration, cholesterol amount and drug content were studied. Span 60 was the most appropriate surfactant, and yielded vesicle size and percentage encapsulation efficiency of 1.3 µm and 98.9%, respectively. The developed system was characterised w.r.t. morphology, transition temperature, drug release, skin permeation and skin irritancy. Proniosomes exhibited a sustained release pattern of BCTin vitro. Skin permeation study revealed high penetration of proniosomes with sustained release of BCT through rat skin. The optimised proniosomal formulation showed enhanced transdermal flux of 16.15 μg/cm2/h as compared to 3.67 μg/cm2/h for drug dispersion. The developed formulations were observed as non-irritant to the rat skin and were found as quite stable at 4 and 25 °C for 90 days w.r.t. vesicle size and drug content. The dried proniosomal formulation could act as a promising alternative to niosomes and preferably for transdermal delivery of BCT. [ABSTRACT FROM AUTHOR]

The aim of the present research work was to investigate the potential of polyamidoamine (PAMAM) dendrimers as oral drug delivery carriers for quercetin, a Biopharmaceutical Classification System (BCS) class II molecule. The aqueous solubility of quercetin was investigated in different generations of dendrimers, i.e. G0, G1, G2 and G3, with varying concentrations (0.1, 0.5, 1, 2 and 4 µM). Then, it was successfully incorporated in PAMAM dendrimers and they were characterized for incorporation efficacy, nature of nanoformulations, size, size distribution, surface morphology and stability.In vitrorelease characteristics of quercetin from all quercetin-PAMAM complexes were studied at 37 °C in phosphate buffer saline (PBS; pH 7.4). Furthermore, the efficacy of quercetin-loaded PAMAM dendrimer was assessed by pharmacodynamic experiment, namely, a carrageenan-induced paw edema model to evaluate the acute activity of this nanocarrier in response to inflammation. It was observed that both generation and the respective concentrations of PAMAM dendrimers showed potential positive effects on solubility enhancement of quercetin. All the quercetin-PAMAM complexes were found to be in nanometeric range (<100 nm) with narrow polydispersity index.In vitrostudy revealed a biphasic release pattern of quercetin which was characterized by an initial faster release followed by sustained release phase and pharmacodynamic study provided the preliminary proof of concept about the potential of quercetin-PAMAM complexes. The study concludes that the dendrimer-based drug delivery system for quercetin has enormous potential to resolve the drug delivery issues associated with it. [ABSTRACT FROM AUTHOR]

Dendrimers are the emerging polymeric architectures that are known for their defined structures, versatility in drug delivery and high functionality whose properties resemble with biomolecules. These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach) respectively. Moreover, high ratio of surface groups to molecular volume has made them a promising synthetic vector for gene delivery. Owing to these properties dendrimers have fascinated the researchers in the development of new drug carriers and they have been implicated in many therapeutic and biomedical applications. Despite of their extensive applications, their use in biological systems is limited due to toxicity issues associated with them. Considering this, the present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity. [ABSTRACT FROM AUTHOR]

Dendrimers are three dimensional polymers, nanoscopic in size, most widely explored in the field of drug delivery in recent times. In order to establish these polymers as controlled and targeted drug delivery systems, they should be non-toxic, biocompatible and biodegradable. The purpose of the present study is to investigate the toxicological profile of fifth generation poly (propyleneimine) dendrimers (PPI) and some of its surface engineered derivatives. Functionalized PPI dendrimers (TPPI, MPPI and TuPPI) were synthesized to mask the primary amino groups responsible for the positive charge and associated toxicity. Each polymer is administered in three different doses: 2.5 mg/kg, 25 mg/kg and 250 mg/kg (i.e., low, intermediate and high dose) to Wister rats, and blood as well as tissue samples were collected after 24 h and 15 days. Decrease in RBC count and hemoglobin content after 24 h, in case of animals administered with PPI suggests hemolytic activity of PPI. Significant increase in SGOT, SGPT and LDH indicates that PPI causes severe damage to the membranes of the various tissues of the body, especially that of the liver leading to the leakage of these marker enzymes in blood. Sections of liver of animals administered with PPI showed signs of tissue degeneration after 24 h. No signs of toxicity were observed in case of animals administered with functionalized PPI. Neither PPI nor its surface engineered derivatives showed any signs of immunogenicity. It can be concluded that functionalization of dendrimers leads to drastic reduction of toxicity and increases biocompatibility. [ABSTRACT FROM AUTHOR]

About 95% of head and neck cancer patients eventually develop radiation-induced dermatitis (RID) during or after treatment. Chronic RID develops in one out of three patients and can appear up to 10 years after the completion of Radiotherapy (RT). Due to their poor transcutaneous permeation and associated side effects, conventional formulations do not display optimum efficacy, requiring the development of novel nano-preparations exhibiting improved efficacy and effectively managing skin damage. Melatonin based nanoemulgel was prepared by using probe sonicator method containing carbopol®934 as gelling agent. By using pseudo-ternary phase diagrams during preformulation development by varying concentration of oil (olive oil), surfactant (tween 80) and co-surfactant (transcutol HP), thus screening best suitable combination which is effective for radiation dermatitis. The optimized formulation was assessed by in vitro characterization namely, FTIR, droplet size, polydispersity index (PDI), viscosity, zeta potential. Further, in vitro drug release profile was analysed by UV-spectrophotometer method and release kinetics was evaluated. Mean droplet size of developed formulation was found 178.8nm, whereas Polydispersity index (PDI) showed 0.175. The formulation was thermodynamically stable, compatible to pH of skin and viscosity was found to be in the range of 9100cps. We measured globule size by the zeta potential and found it to be 23.47mv, signify stability of nanoemulsion. Further, in vitro release studies showed 98.71±0.99% cumulative release of melatonin (MLT) from nanoemulgel over a period of 24 h. Moreover, drug release profile demonstrated that developed formulation follows Higuchi and Korsmeyer-Peppas model, which indicates non-Fickian drug release from matrix system. An optimized melatonin nanoemulgel preparation was evaluated, with all properties indicating that it would be effective and safe for treating damaged skin following radiotherapy. [ABSTRACT FROM AUTHOR]

Objective:  This study aimed to bridge the educational gap in clinical informatics (CI) at the residency level and stimulate interest in CI as a rewarding career path., Methods:  We developed an innovative CI and quality improvement (QI) resident rotation. This rotation replaced traditional QI blocks for Internal Medicine and several other residency programs, offering comprehensive exposure to core informatics and QI principles. The curriculum featured prerecorded didactics, hands-on projects, department meetings, and an optional EPIC SmartUser program. Resident participation and feedback were evaluated through postrotation surveys., Results:  Since its inception on July 1, 2022, 57 residents have completed the rotation, with a majority rating their experience favorably. Residents also valued the educational course content and expressed an increased likelihood of integrating informatics into their future careers., Conclusion:  The rotation has successfully integrated into existing multiple residency programs, demonstrating an effective model for delivering informatics education. Initial outcomes show enhanced resident engagement and competency in CI, promising a progressive impact on the future physician workforce. Continued expansion and evaluation of this rotation are expected to further encourage formal CI training and career interest., Competing Interests: None declared., (Thieme. All rights reserved.)

Breast cancer ranks as the most widespread malignant condition in women, emerging as a primary contributor to mortality. The primary challenges in cancer treatments involve undesirable side effects. Therefore, exploring natural compounds as additional therapy could provide valuable insights. Isoliquiritigenin (ILN), an isoflavonoid featuring a chalcone moiety primarily sourced from Glycyrrhiza species, has garnered increasing interest in breast cancer research. This review aims to provide a comprehensive understanding of ILN's mechanisms of action in breast cancer, drawing from a range of in vitro and in vivo studies. ILN primarily acts by inhibiting angiogenesis, aromatase, inflammation, and cell proliferation, and preventing invasion and metastasis. Mechanistically, it downregulates miR-374a, phosphoinositide-3-kinase-protein kinase B/Akt, maternal embryonic leucine zipper kinase, vascular endothelial growth factor, and estrogen receptor protein levels, and causes enhancement of Wnt inhibitory factor-1, and Unc-51-like kinase 1 expression to treat breast cancer. ILN emerges as a promising natural option, offering therapeutic advantages with minimal side effects. However, it is important to note that current research on ILN is primarily limited to preclinical models, underscoring the need for further investigation to validate its potential efficacy., Competing Interests: Declarations. Ethical approval: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Disclosures: All relevant financial relationships have been mitigated. Disclosure forms are available with this article online.

Internal medicine physicians are increasingly interacting with systems that implement artificial intelligence (AI) and machine learning (ML) technologies. Some physicians and health care systems are even developing their own AI models, both within and outside of electronic health record (EHR) systems. These technologies have various applications throughout the provision of health care, such as clinical documentation, diagnostic image processing, and clinical decision support. With the growing availability of vast amounts of patient data and unprecedented levels of clinician burnout, the proliferation of these technologies is cautiously welcomed by some physicians. Others think it presents challenges to the patient-physician relationship and the professional integrity of physicians. These dispositions are understandable, given the "black box" nature of some AI models, for which specifications and development methods can be closely guarded or proprietary, along with the relative lagging or absence of appropriate regulatory scrutiny and validation. This American College of Physicians (ACP) position paper describes the College's foundational positions and recommendations regarding the use of AI- and ML-enabled tools and systems in the provision of health care. Many of the College's positions and recommendations, such as those related to patient-centeredness, privacy, and transparency, are founded on principles in the ACP Ethics Manual. They are also derived from considerations for the clinical safety and effectiveness of the tools as well as their potential consequences regarding health disparities. The College calls for more research on the clinical and ethical implications of these technologies and their effects on patient health and well-being., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0146.

Various substances possessing radiation scavenging properties, known as radioprotectors, play a crucial role in shielding organisms from the harmful effects of ionizing radiation (IR) by preventing cellular damage caused by free radicals. Initially, synthetic radioprotectors were developed using thiol synthetic compounds. However, among these, only amifostine (WR-2721) underwent clinical testing as a radioprotector. Various composites with different chemical structures other than thiol compounds were also investigated. However, synthetic radioprotectors are known to be associated with severe side effects, which lead to an inclination towards natural substances. Plants and natural products have emerged as promising sources of radioprotectors, renowned for their non-toxic nature across a broad range of doses and their cost-effectiveness. Radioprotectors are employed in diverse pharmaceutical approaches to mitigate the toxicities induced by radiation. The present review encompasses a detailed account of various synthetic and naturally occurring compounds possessing radioprotective properties, and different investigations related to their radioprotective action, ranging from free radicals scavenging to gene therapy, have also been precisely covered. Numerous radioprotectors have different mechanisms of action, and have proven benefits of naturally occurring compounds over chemically synthesized ones., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: The number of surgeries performed in the United States has increased over the past two decades, with a shift to the ambulatory setting. Perioperative complications and mortality pose significant health care burdens. Inadequate preoperative assessment and documentation contribute to communication failure and poor patient outcomes. The aim of this quality improvement project was to design and implement a preoperative evaluation documentation template that not only improved communication during the perioperative pathway but also enhanced the overall user experience., Methods: We implemented a revamped evidence-based documentation template in the electronic medical records of a health care organization across three internal medicine clinics on the downtown campus and seven satellite family medicine clinics. A pre- and postintervention design was used to assess the template utilization rate and clinician satisfaction., Results: The preoperative template utilization rate increased from 51.2% at baseline to 66.5% after the revamped template "went live" ( p  < 0.001). Clinician satisfaction with the preoperative documentation template also significantly increased (30.6 vs. 80.0%, p  < 0.001)., Conclusion: Adopting a user-friendly, evidence-based documentation template can enhance the standardization of preoperative evaluation documentation and reduce the documentation burden., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: In 2011, the American Board of Medical Specialties established clinical informatics (CI) as a subspecialty in medicine, jointly administered by the American Board of Pathology and the American Board of Preventive Medicine. Subsequently, many institutions created CI fellowship training programs to meet the growing need for informaticists. Although many programs share similar features, there is considerable variation in program funding and administrative structures., Objectives: The aim of our study was to characterize CI fellowship program features, including governance structures, funding sources, and expenses., Methods: We created a cross-sectional online REDCap survey with 44 items requesting information on program administration, fellows, administrative support, funding sources, and expenses. We surveyed program directors of programs accredited by the Accreditation Council for Graduate Medical Education between 2014 and 2021., Results: We invited 54 program directors, of which 41 (76%) completed the survey. The average administrative support received was $27,732/year. Most programs (85.4%) were accredited to have two or more fellows per year. Programs were administratively housed under six departments: Internal Medicine (17; 41.5%), Pediatrics (7; 17.1%), Pathology (6; 14.6%), Family Medicine (6; 14.6%), Emergency Medicine (4; 9.8%), and Anesthesiology (1; 2.4%). Funding sources for CI fellowship program directors included: hospital or health systems (28.3%), clinical departments (28.3%), graduate medical education office (13.2%), biomedical informatics department (9.4%), hospital information technology (9.4%), research and grants (7.5%), and other sources (3.8%) that included philanthropy and external entities., Conclusion: CI fellowships have been established in leading academic and community health care systems across the country. Due to their unique training requirements, these programs require significant resources for education, administration, and recruitment. There continues to be considerable heterogeneity in funding models between programs. Our survey findings reinforce the need for reformed federal funding models for informatics practice and training., Competing Interests: None declared., (Thieme. All rights reserved.)

New targeted therapy for triple negative breast cancer (TNBC) is an urgent need, as advanced disease responds poorly to conventional chemotherapy. Genomic and proteomic studies are currently investigating new genes and proteins as promising therapeutic targets. One of such therapeutic targets is a cell cycle regulatory kinase; Maternal Embryonic Leucine Zipper Kinase (MELK), overexpressed in TNBC and correlated with cancer development. We performed molecular docking for virtual screening of chemical libraries (phytochemicals/synthetic drugs) against MELK protein structure and identified 8 phytoconstituents (isoxanthorin, emodin, gamma-coniceine, quercetin, tenuazonic acid, isoliquiritigenin, kaempferol, and Nobiletin) and 8 synthetic drugs (tetrahydrofolic acid, alfuzosin, lansoprazole, ketorolac, ketoprofen, variolin B, orantinib, and firestein) as potential hits interacting with the active site residues of MELK based on bound poses, hydrogen bond, hydrophobic interactions and MM/GBSA binding free energies. ADME and drug-likeness prediction further identified few hits with high drug-likeness properties and were further tested for anti-tumorigenic potential. Two phytochemicals isoliquiritigenin and emodin demonstrated growth inhibitory effects on TNBC MDA-MB-231 cells while much lower effect was observed on non-tumorigenic MCF-10A mammary epithelial cells. Treatment with both molecules downregulated MELK expression, induced cell cycle arrest, accumulated DNA damage and enhanced apoptosis. The study identified isoliquiritigenin and emodin as potential MELK inhibitors and provides a basis for subsequent experimental validation and drug development against cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: J.A. is a member of the Platform for AI Ethics, Netherlands Institute for Standardization (NEN), member of the NEN 7542 workgroup on standardization of medication process data and contract reviewer for the European Commission. S.A.-A. has received consulting fees from AstraZeneca, Agilent Biotechnologies, and Diazyme. A.D.B. has received grants or contracts from NIH and NSF, payment or honoraria from Adelphi University, and travel support from Microsoft. A.J.B. is a cofounder of and consultant to Personalis and NuMedii; consultant to Mango Tree Corporation, and in the recent past, Samsung, 10x Genomics, Helix, Pathway Genomics, and Verinata (Illumina); has served on paid advisory panels or boards for Geisinger Health, Regenstrief Institute, Gerson Lehman Group, AlphaSights, Covance, Novartis, Genentech, and Merck, and Roche; is a shareholder in Personalis and NuMedii; is a minor shareholder in Apple, Meta (Facebook), Alphabet (Google), Microsoft, Amazon, Snap, 10x Genomics, Illumina, Regeneron, Sanofi, Pfizer, Royalty Pharma, Moderna, Sutro, Doximity, BioNtech, Invitae, Pacific Biosciences, Editas Medicine, Nuna Health, Assay Depot, and Vet24seven, and several other non–health-related companies and mutual funds; and has received honoraria and travel reimbursement for invited talks from Johnson and Johnson, Roche, Genentech, Pfizer, Merck, Lilly, Takeda, Varian, Mars, Siemens, Optum, Abbott, Celgene, AstraZeneca, AbbVie, Westat, and many academic institutions, medical or disease specific foundations and associations, and health systems. A.J.B. receives royalty payments through Stanford University, for several patents and other disclosures licensed to NuMedii and Personalis. A.J.B.'s research has been funded by NIH, Peraton (as the prime on an NIH contract), Genentech, Johnson and Johnson, FDA, Robert Wood Johnson Foundation, Leon Lowenstein Foundation, Intervalien Foundation, Priscilla Chan and Mark Zuckerberg, the Barbara and Gerson Bakar Foundation, and in the recent past, the March of Dimes, Juvenile Diabetes Research Foundation, California Governor's Office of Planning and Research, California Institute for Regenerative Medicine, L'Oreal, and Progenity. A.B.C. has received consulting fees from Invitae Corporation. J.K.C. has received grants or contracts from the Office of Rural Health and Office of Healthcare and Equity, VHA. P.L.E. has received grants or contracts from NLM, NIAAA, and NCATS. Oluseyi Fayanju has received grants or contracts from GetSmarter. L.J.F. serves as a consultant to the American Psychiatric Association, has received travel support in relation to that role, and has also received grant support from NIMH. B.R.J. has received stock or stock options from Consent Vault, LLC. V.N.-J. occupies leadership or fiduciary roles with the Academy of Breastfeeding Medicine and West Central Illinois Breastfeeding Task Force. Ross Koppel has received consulting fees from advisors who contemplate investment in EHR companies, payment or honoraria from University at Buffalo, payment for expert testimony from the U.S. Department of Justice, stock or stock options from TrekIT, and occupies editor roles with the Journal of Applied Clinical Informatics and the International Journal of Medical Informatics. B.K. has received payment or honoraria from the Fall DeVos Medical Ethics Colloquy, and travel support to attend CSHI and AMIA conferences. C.U.L. has received royalties or licenses from Springer, has participated in a Data Safety monitoring board conducted by Lipika Samal at Harvard, and has received stock or stock options from Markel and Celanese. Z.C.L. has received consulting fees from Atrius Health, travel support from the University of Washington, Atrius Health, and Jackson Health System. R.J.M. has supported the present manuscript as a Texas Health Resources Clinical Scholar, has received grants or contracts from the Centers for Disease Control and Prevention, Sergey Brin Family Foundation, and Verily Life Sciences, payment or honoraria from Clinical Infectious Diseases, and occupies a leadership role with the Infectious Diseases Society of America. E.R.M. has received grants or contracts from the National Institute on Drug Abuse, the American Medical Association, and the Agency for Healthcare Research and Quality. A.B.N. has received grants or contracts from Royal Phillips and Eli Lilly, consulting fees from Intuity Medical, Roche, Eli Lilly, Sanofi, Greenberg Traurig, and Medtronic, payment or honoraria from The Doctors Company and TCOYD, and payment for expert testimony from AMFS. L.L.N. has received grants or contracts from GetPreCiSe, Florida State University, AHRQ, Baptist Memorial Healthcare Corporation, IBM Watson Health, and NIH/NIDDK. Deepti Pandita has received travel support from AMIA, has a patent pending with WellPulse app, and is a board member of AMIA. Raghuveer Puttagunta is a board member of Pennsylvania Medical Society. Angela Ryan is a member of AMIA and vice chair of the Australasian Institute of Digital Health. K.M.R. occupies a leadership role with the Society of Hospital Medicine Public Policy Committee. Neda Ratanawongsa occupies a leadership role with the San Francisco General Foundation. K.A.S. has received grants from Meds360 and Anonymous Foundation, honoraria from Stanford, travel support from the Society of Family Planning, and is a volunteer board member of the Society of Family Planning. Vignesh Subbian has received a grant from the National Science Foundation and occupies a leadership role with the AMIA ELSI Working Group. Ida Sim is a scientific advisor with Myovant Sciences. A.S. has received grants from NCATS Chicago Institute for Translational Medicine and PCORI Capricorn CRN, occupies leadership roles with the American Medical Informatics Association and IEEE Standards Association, and owns stock from Pfizer, Moderna, and J.B.S. holds leadership roles in AMIA and in the American College of Medical Informatics (ACMI), has received research funding from NIH and the Greenwall Foundation, and honoraria or consulting fees from the University of Kentucky, the University of Wisconsin, and the Icahn Mount Sinai School of Medicine. Peter Winkelstein has received a grant or contract from CTSA. J.X. has participated on a Data Safety Monitoring Board or Advisory Board with AfaSci, Inc. and Develo. C.Z. has received grants or contracts from CVS Foundation and Ariadne Labs, royalties, or licenses from UpToDate, consulting fees from Blue Cross Blue Shield of Massachusetts, and occupies leadership or fiduciary roles with the American Heart Association, Society for Maternal Fetal Medicine, and ACOG.

Background: Self-nanoemulsifying drug delivery system (SNEDDS) has immense potential in oral bioavailability enhancement of lipophilic drugs., Objective: This investigation involves the development of thermodynamically stable and dilutable SNEDDS for tolbutamide, for achieving higher water solubility and enhanced dissolution rate which in turn improves its oral bioavailability., Method: Preliminary solubility studies were carried out and pseudo-ternary phase diagrams were plotted for selection of best ratio of surfactant and co-surfactant. The drug loaded SNEDDS were prepared, characterized w.r.t. refractive index, viscocity, globule size, zeta potential, and TEM, and converted into solid self-nanoemulsifying granules (SSNEGs). These were further characterized and their antidiabetic efficacy in male Wistar rats was evaluated., Results: Solubility studies suggested the suitability of oleic acid as lipid phase; Tween 20 and PEG 400 as optimal surfactant and co-surfactant, respectively for formulation of SNEDDS formulations. The optimal SNEDDS formulation having mean globule diameter, viscosity, polydispersity 58.55 ± 0.2 nm, 26.18 ± 0.2 cps, 0.277 respectively, and infinite dilution capability displayed a highly significant increase in dissolution rate within 5 h compared to pure drug suspension. The SSNEGs showed 1.54 fold increase in drug dissolution rate compared to pure drug. Stability studies revealed no significant change in morphology and globule size. Anti-hyperglycemic activity of tolbutamide loaded SSNEGs in rats showed a significant reduction in elevated blood glucose level with absence of ketone and glucose in urine., Conclusion: The present study demonstrates a successful development of SNEDDS formulation with an overall potential of bioavailability enhancement for tolbutamide, a BCS-II drug., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Diabetes mellitus occurrence has been associated to the modification of the physiological levels of glucose and is often accompanied by several long-term complications, namely neuropathy, nephropathy, retinopathy, cataract, and cardiovascular. Aldose reductase (AR) is an enzyme of aldoketo reductase super-family that catalyzes the conversion of glucose to sorbitol in the polyol pathway of glucose metabolism. In this context, aldose reductase inhibitors (ARIs) have received much attention worldwide. Decreased sorbitol flux through polyol pathway by ARIs could be an emerging target for the management of major complications of diabetes. The present review article describes a brief overview of the role of aldose reductase in the diabetic complications, advances achieved on ARIs and their potential use in the treatment and management of the major diabetic complications such as cataract, retinopathy, neuropathy, nephropathy and cardiovascular. The ARIs developed vary structurally, and representative structural classes of ARIs include i) carboxylic acid derivatives (such as Epalrestat, Alrestatin, Zopalrestat, Zenarestat, Ponalrestat, Lidorestat, and Tolrestat), ii) spirohydantoins and related cyclic amides (such as Sorbinil, Minalrestat, and Fidarestat), and iii) phenolic derivatives (related to Benzopyran-4-one and Chalcone). Among these inhibitors, Epalrestat is the only commercially available inhibitor till date. In addition, some other ARIs such as Sorbinil and Ranirestat had been advanced into late stage of clinical trials and found to be safe for human use. The role of various natural ARIs in management of diabetic complications will be discussed. Adapting ARIs could prevent sepsis complications, prevent angiogenesis, ameliorate mild or asymptomatic diabetic cardiovascular autonomic neuropathy and appear to be a promising strategy for the treatment of endotoxemia and other ROS-induced inflammatory diseases. The role of ARIs in non-diabetic diseases will also be discussed.

Metabolic syndrome is a disorder described by reduced insulin sensitivity, overweight, hyperlipidaemia, high blood pressure and myocardial disorders, mainly due to high fat diet and lack of physical activity. The peroxisome proliferator activated receptors (PPARs) are type II nuclear hormone receptors that regulate a number of processes in living systems, such as metabolism of carbohydrates and fatty acids, growth and differentiation of cell, and inflammatory reactions. Alpha, gamma and delta are the three distinct isoforms of PPAR. The stimulation of PPARδ alters body's energy fuel preference from glucose to fat. The PPARδ isoform is expressed ubiquitously in all tissues, especially in those tissues which involved in metabolism of lipids like adipose tissue, liver, kidney, and muscle. Currently, PPARδ is an emerging therapeutic target for the pharmacological therapy of disorders associated with metabolic syndrome. Several PPARδ selective agonists had been reported in last ten years, many of them had been advanced into the late phase of clinical trials such as Endurobol (GW501516). However, no PPARδ agonists are yet approved for human use. The present work had been planned to cover wide variety of PPARδ agonists reported till now along with their potential role to tackle various metabolic disorders. The present review has been planned to focus mainly the most popular PPARδ agonists.

Mesenchymal stem cells (MSCs) can be isolated from several tissues in the body, have the ability to self-renewal, show immune suppressive properties and are multipotent, being able to generate various cell types. At present, due to their intrinsic characteristics, MSCs are considered very promising in the area of tissue engineering and regenerative medicine. In this context, genetic modification can be a powerful tool to control the behavior and fate of these cells and be used in the design of new cellular therapies. Viral systems are very effective in the introduction of exogenous genes inside MSCs. However, the risks associated with their use are leading to an increasing search for non-viral approaches to attain the same purpose, even if MSCs have been shown to be more difficult to transfect in this way. In the past few years, progress was made in the development of chemical and physical methods for non-viral gene delivery. Herein, an overview of the application of those methods specifically to MSCs is given and their use in tissue engineering and regenerative medicine therapeutic strategies highlighted using the example of bone tissue. Key issues and future directions in non-viral gene delivery to MSCs are also critically addressed.