Heterocyclic Compounds as Dipeptidyl Peptidase-IV Inhibitors with Special Emphasis on Oxadiazoles as Potent Anti-Diabetic Agents.

Dipeptidyl peptidase-IV (DPP-IV) inhibitors, often known as gliptins, have been used to treat type 2 diabetes mellitus (T2DM). They may be combined with other medications as an additional treatment or used alone as a monotherapy. In addition to insulin, sulfonylureas, thiazolidinediones, and metformin, these molecules appear as possible therapeutic options. Oxadiazole rings have been employed in numerous different ways during drug development efforts. It has been shown that including them in the pharmacophore increases the amount of ligand that may be bound. The exceptional hydrogen bond acceptor properties of oxadiazoles and the distinct hydrocarbon bonding potential of their regioisomers have been established. Beside their anti-diabetic effects, oxadiazoles display a wide range of pharmacological properties. In this study, we made the assumption that molecules containing oxadiazole rings may afford a different approach to the treatment of diabetes, not only for controlling glycemic levels but also for preventing atherosclerosis progression and other complications associated with diabetes. It was observed that oxadiazole fusion with benzothiazole, 5-(2,5,2-trifluoroethoxy) phenyl, ß-homophenylalanine, 2-methyl-2-{5-(4-chlorophenyl), diamine-bridged bis-coumarinyl, 5-aryl-2-(6'-nitrobenzofuran-2'-yl), nitrobenzofuran, and/or oxindole leads to potential anti-diabetic activity.

Involvement of Resveratrol against Brain Cancer: A Combination Strategy with a Pharmaceutical Approach.

A brain tumor (BT) is a condition in which there is growth or uncontrolled development of the brain cells, which usually goes unrecognized or is diagnosed at the later stages. Since the mechanism behind BT is not clear, and the various physiological conditions are difficult to diagnose, the success rate of BT is not very high. This is the central issue faced during drug development and clinical trials with almost all types of neurodegenerative disorders. In the first part of this review, we focus on the concept of brain tumors, their barriers, and the types of delivery possible to target the brain cells. Although various treatment methods are available, they all have side effects or toxic effects. Hence, in the second part, a correlation was made between the use of resveratrol, a potent antioxidant, and its advantages for brain diseases. The relationship between brain disease and the blood-brain barrier, multi-drug resistance, and the use of nanomedicine for treating brain disorders is also mentioned. In short, a hypothetical concept is given with a background investigation into the use of combination therapy with resveratrol as an active ingredient, the possible drug delivery, and its formulation-based approach.

Anti-ribosomal P antibody: a multicenter study in childhood-onset systemic lupus erythematosus patients.

Objectives Anti-ribosomal P protein (anti-P) autoantibodies are highly specific for systemic lupus erythematosus (SLE). However, the evaluation of this autoantibody in childhood-onset SLE (cSLE) populations has been limited to a few small series, hampering the interpretation of the clinical and laboratorial associations. Therefore, the objective of this multicenter cohort study was to evaluate demographic, clinical/laboratorial features, and disease damage score in cSLE patients with and without the presence of anti-P antibody. Methods This was a retrospective multicenter study performed in 10 pediatric rheumatology services of São Paulo state, Brazil. Anti-P antibodies were measured by ELISA in 228 cSLE patients. Results Anti-P antibodies were observed in 61/228 (27%) cSLE patients. Frequencies of cumulative lymphadenopathy (29% vs. 15%, p = 0.014), acute confusional state (13% vs. 5%, p = 0.041), mood disorder (18% vs. 8%, p = 0.041), autoimmune hemolytic anemia (34% vs. 15%, p = 0.001), as well as presence of anti-Sm (67% vs. 40%, p = 0.001), anti-RNP (39% vs. 21%, p = 0.012) and anti-Ro/SSA antibodies (43% vs. 25%, p = 0.016) were significantly higher in cSLE patients with anti-P antibodies compared to those without these autoantibodies. A multiple regression model revealed that anti-P antibodies were associated with autoimmune hemolytic anemia (odds ratio (OR) = 2.758, 95% confidence interval (CI): 1.304-5.833, p = 0.008) and anti-Sm antibody (OR = 2.719, 95% CI: 1.365-5.418, p = 0.004). The SLICC/ACR damage index was comparable in patients with and without anti-P antibodies ( p = 0.780). Conclusions The novel association of anti-P antibodies and autoimmune hemolytic anemia was evidenced in cSLE patients and further studies are necessary to determine if anti-P titers may vary with this hematological manifestation.

Complete physical mapping of IL6 reveals a new marker associated with chronic periodontitis.

BACKGROUND AND OBJECTIVE: Interleukin-6 (IL-6) is a powerful stimulator of osteoclast differentiation and bone resorption. Production of IL-6 is modulated by polymorphisms, and higher levels of this cytokine are found locally in patients with chronic periodontitis. In this study we performed a modern approach - Complete physical mapping of the IL6 gene - to identify the polymorphisms associated with chronic periodontitis in a southern Brazilian population sample. MATERIAL AND METHODS: One-hundred and nine individuals of both genders (mean age: 41.5 ± 8.5 years) were divided into a study group (56 participants with periodontitis) and a control group (53 individuals without periodontitis). After collection and purification of DNA, nine tag single nucleotide polymorphisms (SNPs; rs1524107, rs2069835, rs2069837, rs2069838, rs2069840, rs2069842, rs2069843, rs2069845 and rs2069849) covering the entire gene were selected according to the information available on the International HapMap Project website and evaluated using real-time PCR. RESULTS: Differences in the distribution of the following parameters were statistically significant between study and control groups: number of teeth (p = 0.030); probing depth (p < 0.001); clinical attachment level (p < 0.001); gingival index (p < 0.001); plaque index (p = 0.003); calculus index (p < 0.001); and dental mobility (p < 0.001). It was found that marker rs2069837 (located in intron 2 of IL6) under G dominant was associated with protection against chronic periodontitis in a Brazilian population in the presence of clinical variables, such as visible plaque, dentist visit frequency and dental floss use, and was suggested for the first time as a marker of susceptibility to chronic periodontitis. CONCLUSION: Complete physical mapping of IL6 (using tag SNPs) was carried out for the first time, unveiling allele G of polymorphism rs2069837 (located in the second intron of IL6) as a suggestive marker of protection against chronic periodontitis in a Brazilian population.

[MODen: Psychoeducationnal therapeutic group program for schizophrenic patients, based on nutritional balance and pleasure, using cognitive functions: A pilot study]. / MODen : programme d'éducation thérapeutique dans la schizophrénie centré sur l'équilibre alimentaire et le plaisir, sollicitant les fonctions cognitives : étude pilote.

INTRODUCTION: Schizophrenia causes psychological difficulties (with positive and/or negative symptoms) as well as cognitive disabilities (attention, memory, executive functions and social cognition). Moreover, 40 to 60% of patients suffer from an excess of weight or obesity (due to bad eating habits, eating disorders or medication). All these difficulties impair their autonomy and their insertion into the society. In this context, setting-up a therapeutic tool, which may have cognitive benefits seems relevant. Thus, MODen is a therapeutic educational tool whose aim is to improve cognitive functions and the symptoms by using "nutritional balance" as an aid. METHOD: In this treatment program, two therapists lead a group of 5 to 8 patients which group meets once a week during two to four hours for 16 weeks, divided in 4 cycles. The first three weeks of each cycle consists of theoretical instruction: patients talk about their eating habits, information is given about nutritional balance and preparation of meals. In the different cycles, flexibility, planning, memory and attention are trained. For instance, the work on categorisation of foods and nutritional balance allow enhancing flexibility abilities. Writing down the lists of different ingredients needed for one week's meals and preparation of meals train planning abilities. MODen also takes into account ecological issues such as the limited budget of patients to do their shopping (this budget is around 4 euros per meal in France). The budget is also linked to planning abilities and reasoning. Finally, during the last session of each cycle the group prepares a meal (from the shopping to cooking). This last session is all about sharing and social cognition abilities. By the end of the program, patients will have prepared four meals together. Also "homework" has to be done each week in order to facilitate memorisation of what has been learned during the last session and to prepare the beginning of the next session. RESULTS: In a pilot study with 8 patients with schizophrenia (DSM-IV), improvements in PANSS negative symptoms and disorganization (respectively P<0.02; P<0.02) were observed. An underlying improvement at BECS scores was also observed (P<0.08). Regarding those preliminary results as well as the ecological qualities of this program, this therapeutic tool could be relevant in the treatment of patients with schizophrenia.

Ten steps for proper peripheral nerve handling during inguinal hernia surgery.

INTRODUCTION: Post-inguinal pain after a hernia surgery is prevalent and can be quite frustrating for the surgeon and patient alike. There are several sources for possible post-operative inguinal pain after a successful hernia repair; however, in the setting where a recurrent inguinal hernia is not present, it is likely related to the nerves in the inguinal canal or pelvis. Chronic inguinal groin pain after hernia repairs have been reported in a high percentage of patients following inguinal hernia surgery despite being one of the most common procedures performed annually in the USA and worldwide. MATERIALS AND METHODS: We present ten of the basic concepts utilized by peripheral nerve surgeons to limit nerve injury, which can easily be applied to open inguinal hernia surgery with or without mesh, starting with the firm understanding of the inguinal anatomy to addressing the nerves, meticulous placement of the mesh and the active revision of the surrounding structures and nerve position before closure. CONCLUSIONS: Understanding the proper handling of the inguinal nerves during hernia surgery can decrease the incidence of post-operative chronic pain by employing microsurgical concepts to day-to-day surgical procedures and prevent complications in an extensive set of patients.

Angiogenic footprints in diabetic retinopathy: opportunities for drug development.

Diabetic retinopathy is one of the withering disorders that has been making the lives of patients miserable. Arising as a result of chronic high blood sugar levels in diabetes patients, retinopathy has become a major reason causing permanent blindness, retinal detachment, vitreous humor, rage, or glaucoma among patients. Angiogenesis being the major culprit behind the development of this condition is the growth of new blood vessels from the earlier ones existing. The abnormal growth and poor development of blood vessels also lead to aggravation of the conditions, with vascular endothelial growth factor (VEGF) playing a major role in the process. Various anti-angiogenic therapies or anti-VEGF therapies are being explored for the treatment of this condition. 4 widely explored drugs being-Bevacizumab, pegaptanib sodium, ranibizumab, and aflibercept. The review article tries to summarize studies illustrating the efficacy of these drugs in the treatment of diabetic retinopathy along with some of the herbal therapeutic paradigms displaying anti-angiogenic action that is being used to treat this condition.

Atmospheric pollution: influence on hospital admissions in paediatric rheumatic diseases.

OBJECTIVE: To investigate the lag structure effects from exposure to atmospheric pollution in acute outbursts in hospital admissions of paediatric rheumatic diseases (PRDs). METHODS: Morbidity data were obtained from the Brazilian Hospital Information System in seven consecutive years, including admissions due to seven PRDs (juvenile idiopathic arthritis, systemic lupus erythematosus, dermatomyositis, Henoch-Schönlein purpura, polyarteritis nodosa, systemic sclerosis and ankylosing spondylitis). Cases with secondary diagnosis of respiratory diseases were excluded. Daily concentrations of inhaled particulate matter (PM(10)), sulphur dioxide (SO(2)) nitrogen dioxide (NO(2)), ozone (O(3)) and carbon monoxide (CO) were evaluated. Generalized linear Poisson regression models controlling for short-term trend, seasonality, holidays, temperature and humidity were used. Lag structures and magnitude of air pollutants' effects were adopted to estimate restricted polynomial distributed lag models. RESULTS: The total number of admissions due to acute outbursts PRD was 1,821. The SO(2) interquartile range (7.79 µg/m(3)) was associated with an increase of 1.98% (confidence interval 0.25-3.69) in the number of hospital admissions due to outcome studied after 14 days of exposure. This effect was maintained until day 17. Of note, the other pollutants, with the exception of O(3), showed an increase in the number of hospital admissions from the second week. CONCLUSION: This study is the first to demonstrate a delayed association between SO(2) and PRD outburst, suggesting that oxidative stress reaction could trigger the inflammation of these diseases.

A Background Search on the Potential Role of Scutellaria and Its Essential Oils.

Scutellaria (Lamiaceae), which contains over 350 species, usually known as skullcaps, is found throughout Europe, the United States, and East Asia. In traditional Chinese medicine, several species are used to wipe out heat-evil and remove surface ills (TCM). The current study examines the ethnopharmacology, biological activity, and chemical substances associated with Scutellaria species. More than 295 chemicals, including flavonoids and diterpenes, have been identified. Scutellaria and its active principles have been shown in studies to have a wide range of pharmacological activities, including antioxidant, antimicrobial, antifeedant, phytotoxic, acaricidal toxicity, antibacterial, anti-inflammatory, and antianalgesic activities. Currently, effective monomeric compounds or active components from Scutellaria have been evaluated for pharmacological action in vivo and in vitro. More data facilitates applications and exploitation of novel medication development.

Locally Applied Repositioned Hormones for Oral Bone and Periodontal Tissue Engineering: A Narrative Review.

Bone and periodontium are tissues that have a unique capacity to repair from harm. However, replacing or regrowing missing tissues is not always effective, and it becomes more difficult as the defect grows larger. Because of aging and the increased prevalence of debilitating disorders such as diabetes, there is a considerable increase in demand for orthopedic and periodontal surgical operations, and successful techniques for tissue regeneration are still required. Even with significant limitations, such as quantity and the need for a donor area, autogenous bone grafts remain the best solution. Topical administration methods integrate osteoconductive biomaterial and osteoinductive chemicals as hormones as alternative options. This is a promising method for removing the need for autogenous bone transplantation. Furthermore, despite enormous investigation, there is currently no single approach that can reproduce all the physiologic activities of autogenous bone transplants. The localized bioengineering technique uses biomaterials to administer different hormones to capitalize on the host's regeneration capacity and capability, as well as resemble intrinsic therapy. The current study adds to the comprehension of the principle of hormone redirection and its local administration in both bone and periodontal tissue engineering.

Multidrug Resistance of Cancer Cells and the Vital Role of P-Glycoprotein.

P-glycoprotein (P-gp) is a major factor in the multidrug resistance phenotype in cancer cells. P-gp is a protein that regulates the ATP-dependent efflux of a wide range of anticancer medicines and confers resistance. Due to its wide specificity, several attempts have been made to block the action of P-gp to restore the efficacy of anticancer drugs. The major goal has been to create molecules that either compete with anticancer medicines for transport or function as a direct P-gp inhibitor. Despite significant in vitro success, there are presently no drugs available in the clinic that can "block" P-gp-mediated resistance. Toxicity, unfavourable pharmacological interactions, and a variety of pharmacokinetic difficulties might all be the reason for the failure. On the other hand, P-gp has a significant effect in the body. It protects the vital organs from the entry of foreign bodies and other toxic chemicals. Hence, the inhibitors of P-gp should not hinder its action in the normal cells. To develop an effective inhibitor of P-gp, thorough background knowledge is needed in this field. The main aim of this review article was to set forth the merits and demerits of the action of P-gp on cancer cells as well as on normal cells. The influence of P-gp on cancer drug delivery and the contribution of P-gp to activating drug resistance were also mentioned.

Recent Advances in Adsorptive Nanocomposite Membranes for Heavy Metals Ion Removal from Contaminated Water: A Comprehensive Review.

Water contamination is one of the most urgent concerns confronting the world today. Heavy metal poisoning of aquatic systems has piqued the interest of various researchers due to the high toxicity and carcinogenic consequences it has on living organisms. Due to their exceptional attributes such as strong reactivity, huge surface area, and outstanding mechanical properties, nanomaterials are being produced and employed in water treatment. In this review, recent advances in the use of nanomaterials in nanoadsorptive membrane systems for wastewater treatment and heavy metal removal are extensively discussed. These materials include carbon-based nanostructures, metal nanoparticles, metal oxide nanoparticles, nanocomposites, and layered double hydroxide-based compounds. Furthermore, the relevant properties of the nanostructures and the implications on their performance for water treatment and contamination removal are highlighted. The hydrophilicity, pore size, skin thickness, porosity, and surface roughness of these nanostructures can help the water permeability of the nanoadsorptive membrane. Other properties such as surface charge modification and mechanical strength can improve the metal adsorption effectiveness of nanoadsorptive membranes during wastewater treatment. Various nanocomposite membrane fabrication techniques are also reviewed. This study is important because it gives important information on the roles of nanomaterials and nanostructures in heavy metal removal and wastewater treatment.

Drug-Loaded Chitosan Scaffolds for Periodontal Tissue Regeneration.

Chitosan is a natural anionic polysaccharide with a changeable architecture and an abundance of functional groups; in addition, it can be converted into various shapes and sizes, making it appropriate for a variety of applications. This article examined and summarized current developments in chitosan-based materials, with a focus on the modification of chitosan, and presented an abundance of information about the fabrication and use of chitosan-derived products in periodontal regeneration. Numerous preparation and modification techniques for enhancing chitosan performance, as well as the uses of chitosan and its metabolites, were reviewed critically and discussed in depth in this study. Chitosan-based products may be formed into different shapes and sizes, considering fibers, nanostructures, gels, membranes, and hydrogels. Various drug-loaded chitosan devices were discussed regarding periodontal regeneration.

Application of Nano-Inspired Scaffolds-Based Biopolymer Hydrogel for Bone and Periodontal Tissue Regeneration.

This review's objectives are to provide an overview of the various kinds of biopolymer hydrogels that are currently used for bone tissue and periodontal tissue regeneration, to list the advantages and disadvantages of using them, to assess how well they might be used for nanoscale fabrication and biofunctionalization, and to describe their production processes and processes for functionalization with active biomolecules. They are applied in conjunction with other materials (such as microparticles (MPs) and nanoparticles (NPs)) and other novel techniques to replicate physiological bone generation more faithfully. Enhancing the biocompatibility of hydrogels created from blends of natural and synthetic biopolymers can result in the creation of the best scaffold match to the extracellular matrix (ECM) for bone and periodontal tissue regeneration. Additionally, adding various nanoparticles can increase the scaffold hydrogel stability and provide a number of biological effects. In this review, the research study of polysaccharide hydrogel as a scaffold will be critical in creating valuable materials for effective bone tissue regeneration, with a future impact predicted in repairing bone defects.

Exploration of Site-Specific Drug Targeting-A Review on EPR-, Stimuli-, Chemical-, and Receptor-Based Approaches as Potential Drug Targeting Methods in Cancer Treatment.

Cancer has been one of the most dominant causes of mortality globally over the last few decades. In cancer treatment, the selective targeting of tumor cells is indispensable, making it a better replacement for conventional chemotherapies by diminishing their adverse side effects. While designing a drug to be delivered selectively in the target organ, the drug development scientists should focus on various factors such as the type of cancer they are dealing with according to which drug, targeting moieties, and pharmaceutical carriers should be targeted. All published articles have been collected regarding cancer and drug-targeting approaches from well reputed databases including MEDLINE, Embase, Cochrane Library, CENTRAL and ClinicalTrials.gov, Science Direct, PubMed, Scopus, Wiley, and Springer. The articles published between January 2010 and December 2020 were considered. Due to the existence of various mechanisms, it is challenging to choose which one is appropriate for a specific case. Moreover, a combination of more than one approach is often utilized to achieve optimal drug effects. In this review, we have summarized and highlighted central mechanisms of how the targeted drug delivery system works in the specific diseased microenvironment, along with the strategies to make an approach more effective. We have also included some pictorial illustrations to have a precise idea about different types of drug targeting. The core contribution of this work includes providing a cancer drug development scientist with a broad preliminary idea to choose the appropriate approach among the various targeted drug delivery mechanisms. Also, the study will contribute to improving anticancer treatment approaches by providing a pathway for lesser side effects observed in conventional chemotherapeutic techniques.

Endoscopic submucosal dissection in a European setting. A multi-institutional report of a technique in development.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a technique for "en bloc" resection of superficial tumors of the gastrointestinal tract. In France, experience with this technique is still limited. We wanted to assess the development of ESD in France, with special attention to short term outcomes. PATIENTS AND METHODS: Members of the Société Française d'Endoscopie Digestive (SFED) who declared performing ESD reported their cases prospectively on a voluntary basis. Demographic, clinical, and technical data, and the results of immediate complications were collected. Case reports were completed prospectively by each investigator before pooled analysis. RESULTS: A total of 188 consecutive case reports were collected from 16 centers. The median case mix per center was 6 patients (range 1-43). The lesion sites treated by ESD were the stomach (n = 75), esophagus (n = 27), duodenum (n = 1), cecum (n = 2), right colon (n = 3), transverse colon (n = 5), sigmoid (n = 3), and rectum (n = 72). The median size of the lesions was 26 mm (range 2-150 mm). En bloc resection was achieved in 77.1% of cases, with complete R0 resection in 72.9%. Histopathology results showed high grade dysplasia or superficial cancer in 71.2%. The median duration of ESD was 105 minutes (range 20-450 minutes). The short term morbidity was 29.2% including 34 cases of perforation (18.1%), and 21 hemorrhages (11.2%) during the 24 hours following ESD, 89% of which were managed conservatively or endoscopically. CONCLUSION: In this early experience, the feasibility of ESD appeared to be good but R0 resection and complication rates did not match those reported by Japanese authors and must be improved by an extended practice.

[Chronic hydarthrosis of the knee in a Tunisian patient: tabetic arthropathy]. / Epanchement articulaire récidivant du genou chez un tunisien.

Tabetic arthropathy (TA) is a type of neuropathic arthropathy that has become rare. The purpose of this report is to describe a case of tabetic arthropathy involving the knee. A 53-year-old man was hospitalized for painless right knee arthropathy. Clinical examination demonstrated hydarthrosis of the right knee, peripheral neuropathic syndrome of the lower limbs, and paralysis of the IXth and Xth cranial pairs. Plain radiography showed the presence of lytic lesions in the internal femoral condyle and tibial plateau. Syphilitic serology tests were positive in the blood and cerebrospinal fluid.

Magnetic and magneto-optical properties of assembly of nanodots obtained from solid-state dewetting of ultrathin cobalt layer.

An assembly of randomly organized cobalt nanoparticles were obtained by solid-state dewetting of a 3 nm-thick cobalt layer. Vibrating sample magnetometry and Brillouin light scattering techniques were used to investigate both their static and dynamic behaviors with respect to the initial native cobalt layer. The measurements obtained from the assembly of the obtained nanodots were analyzed by means of shape anisotropy contribution. The Brillouin spectra revealed an unusual reversed Stokes/anti-Stokes line height asymmetry comparing to that observed on the native layer. The effective optical properties of the nanodots, combined with the relation between mean field and inside-dot field allowed explaining the observed reversed height asymmetry. The assembly of nanodots behave as an effective magnetic and optical medium where these properties can be tuned by the elaboration process.

Performance of carbon arc-discharge nanotubes to hydrogen energy storage.

Adsorption properties of gram-scale samples of different kind of arc discharge nanotubes were studied, namely: (A) raw collaret collected on the cathode, (B) raw soots collected on the lateral reactor wall, (C) thermally treated soot, and (D) thermally then chemically treated soot. The morphology, structure, and composition of these materials were characterized by SEM, TEM, TGA, and BET. In addition, hydrogen adsorption isotherms were recorded experimentally for A, B, and D samples over the pressure range of 0 to 55 bar at ambient temperature. Our experiments indicated a maximum-yet weak-hydrogen storage at room temperature of approximately 0.13 H2 wt% for the purified product (D).