Association of 24 bp Duplication of Human CHIT1 Gene with Asthma in a Heterozygous Population of North India: A Case–Control Study

Purpose

CHIT1 is expressed by pulmonary macrophages, which is typically the site of entry for many environmental fungi that may increase the risk of pulmonary fungal infection and lead to hypersensitivity. The conserved expression of this gene in humans suggests its physiological importance in the mammalian lung.

Methods

The present study was conducted with a total of 964 subjects, including 483 healthy controls and 481 asthma patients. DNA samples were extracted from blood, and the genotyping was done using polymerase chain reaction method.

Results

Statistical analysis revealed that the 24 bp duplication in CHIT1 gene polymorphism shows highly significant association in heterozygous (wild/dup) genotype with OR 1.74, 95 % CI (1.29–2.36), and p = 0.000. However, the homozygous mutant genotype (dup/dup) was found to be non-significant with OR 1.06, 95 % CI (0.69–1.63), and p = 0.786. The combination of both wild/dup and dup/dup was also found to be highly significant with OR 1.57, 95 % CI (1.18–2.11), and p = 0.002.

Conclusions

This is the first study conducted in India which reports a significant association between 24 bp duplication in CHIT1 gene polymorphism and asthma in the studied North Indian population.     

Smoldering multiple myeloma: present position and potential promises

Since smoldering multiple myeloma (SMM) was first described over three decades ago based on a case series of six patients, its definition and our understanding of the entity have evolved considerably. The risk of progression to symptomatic myeloma (MM) varies greatly among individuals diagnosed with myeloma precursor disease. Epidemiologic, molecular, flow cytometric and radiological techniques have demonstrated that this transformation to MM from precursor states is not sudden but rather a continuous overlapping series of events with evidence of end‐organ damage that could manifest in the earliest stages of disease. Contemporary antimyeloma therapies can yield rapid, deep, and durable responses with manageable toxicities, and molecular‐cell‐based measures are now available to rule out minimal residual disease. With this information, clinical studies with correlative measures can now be developed to test the fundamental hypothesis that intervention in early myeloma may provide a measurable clinical benefit to patients by either delaying progression or eradicating plasma cell clones.     

Novel analogs of sulfasalazine as system xc− antiporter inhibitors: Insights from the molecular modeling studies

System x_c⁻ (Sx_c⁻), a cystine-glutamate antiporter, is established as an interesting target for the treatment of several pathologies including epileptic seizures, glioma, neurodegenerative diseases, and multiple sclerosis. Erastin, sorafenib, and sulfasalazine (SSZ) are a few of the established inhibitors of Sx_c⁻. However, its pharmacological inhibition with novel and potent agents is still very much required due to potential issues, for example, potency, bioavailability, and blood–brain barrier (BBB) permeability, with the current lead molecules such as SSZ. Therefore, in this study, we report the synthesis and structure–activity relationships (SAR) of SSZ derivatives along with molecular docking and dynamics simulations using the developed homology model of xCT chain of Sx_c⁻ antiporter. The generated homology model attempted to address the limitations of previously reported comparative protein models, thereby increasing the confidence in the computational modeling studies. The main objective of the present study was to derive a suitable lead structure from SSZ eliminating its potential issues for the treatment of glioblastoma multiforme (GBM), a deadly and malignant grade IV astrocytoma. The designed compounds with favorable Sx_c⁻ inhibitory activity following in vitro Sx_c⁻ inhibition studies, showed moderately potent cytotoxicity in patient-derived human glioblastoma cells, thereby generating potential interest in these compounds. The xCT-ligand model can be further optimized in search of potent lead molecules for novel drug discovery and development studies.     

The Ontogeny of Masticatory Muscle Architecture in Microcebus murinus

The masticatory apparatus has been the focus of many studies in comparative anatomy—especially analyses of skulls and teeth, but also of the mandibular adductor muscles which are responsible for the production of bite force and the movements of the mandible during food processing and transport. The fiber architecture of these muscles has been correlated to specific diets (e.g., prey size in felids) and modes of foraging (e.g., tree gouging in marmosets). Despite the well-elucidated functional implications of this architecture, little is known about its ontogeny. To characterize age-related myological changes, we studied the masticatory muscles in a large (n = 33) intraspecific sample of a small, Malagasy primate, Microcebus murinus including neonatal through geriatric individuals. We removed each of the mandibular adductors and recorded its mass as well as other linear measurements. We then chemically dissected each muscle to study its architecture—fascicle length and physiological cross-sectional area (PCSA) which relate to stretch (gape) and force capabilities, respectively. We observed PCSA and muscle mass to increase rapidly and plateau in adulthood through senescence. Fascicle lengths remained relatively constant once maximal length was reached, which occurred early in life, suggesting that subsequent changes in PCSA are driven by changes in muscle mass. Quadratic curvilinear models of each of the architectural variables of all adductors combined as well as individual muscles regressed against age were all significant. Anat Rec, 303:1364–1373, 2020. © 2019 American Association for Anatomy     

The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium

Glucagon like peptide-1 (GLP-1) is an incretin hormone that is in the pipeline for type 2 diabetes mellitus (T2DM) therapy. However, oral administration of GLP-1 is hindered by the harsh conditions of the gastrointestinal tract and poor bioavailability. In this study, three nanosystems composed by three different biomaterials (poly(lactide-co-glycolide) polymer (PLGA), Witepsol E85 lipid (solid lipid nanoparticles, SLN) and porous silicon (PSi) were developed and loaded with GLP-1 to study their permeability in vitro. All the nanoparticles presented a size of approximately 200 nm. The nanoparticles' interaction with the mucus and the intestinal cells were enhanced after coating with chitosan (CS). PSi nanosystems presented the best association efficiency (AE) and loading degree (LD), even though a high AE was also observed for PLGA nanoparticles and SLN. Among all the nanosystems, PLGA and PSi were the only nanoparticles able to sustain the release of GLP-1 in biological fluids when coated with CS. This characteristic was also maintained when the nanosystems were in contact with the intestinal Caco-2 and HT29-MTX cell monolayers. The CS-coated PSi nanoparticles showed the highest GLP-1 permeation across the intestinal in vitro models. In conclusion, PLGA + CS and PSi + CS are promising nanocarriers for the oral delivery of GLP-1.     

Vitamin E Supplementation,Superoxide Dismutase Status,and Outcome of Scaling and Root Planing in Patients With Chronic Periodontitis: A Randomized Clinical Trial

Background: This study investigates the levels of superoxide dismutase (SOD) activity in serum and saliva of patients with chronic periodontitis (CP). In addition, the outcome of scaling and root planing (SRP) with and without vitamin E supplementation is evaluated in terms of changes in periodontal parameters and SOD activity in patients with CP. Methods: Serum and salivary SOD activity in 38 patients with CP were compared with those of 22 systemically and periodontally healthy individuals (control group). At periodontal examination, serum and saliva samples were obtained. Patients with CP were randomly divided into treatment groups 1 (TG‐1) and 2 (TG‐2). SRP was performed for both groups, and TG‐2 also received 200 mg (300 IU) vitamin E every other day. Periodontal parameters and SOD activity were evaluated after 3 months. SOD activity was determined using an SOD assay and enzyme‐linked immunosorbent assay reader at 450 nm. Results: SOD activity in both serum (P <0.05) and saliva (P <0.001) was lower in patients with CP compared with controls. After 3 months of follow‐up, SOD activity improved in both treatment groups; however, the improvement in TG‐2 was higher than in TG‐1, along with more improvement in periodontal parameters. Serum SOD levels in TG‐2 increased even above the level of the control group. Conclusions: Systemic and local SOD levels are lowered in CP. Adjunctive vitamin E supplementation improves periodontal healing as well as antioxidant defense.