Evaluation of time to sputum smear conversion and its association with treatment outcomes among drug-resistant tuberculosis patients: a retrospective record-reviewing study.

Background: This study examined the time to sputum smear and culture conversion and determinants of conversion, as well as variables associated with treatment outcomes among drug-resistant pulmonary tuberculosis (DR-PTB) cases. Methods: The electronic database and written medical records of patients were utilized to assess the sociodemographic, clinical, microbiological, and treatment characteristics and outcomes of study participants. Results: Among 736 patients with pulmonary tuberculosis (PTB), the mean age was 36.5 ± 16.5 years, with males comprising 53.4% and a mean weight of 47.76 ± 11.97 kg. The median time period for sputum smear conversion and sputum culture conversion was a month. The first-month culture conversion (p < 0.001, aOR = 5.817, and 95% CI = 3.703-9.138) was the determinant of sputum smear conversion and receiver operating curve analysis with AUC = 0.881, 95% CI = 0.855-0.907, and p < 0.001, which showed a high level of predictive ability for the regression model for the initial sputum smear conversion. However, the first-month sputum conversion (p < 0.001, aOR = 7.446, and 95% CI = 4.869-11.388) was attributed to sputum culture conversion, and the model has shown excellent predictive ability for regression with ROC curve analysis demonstrating AUC = 0.862, 95% CI = 0.835-0.889, and p < 0.001. A total of 63.2% of patients showed favorable treatment outcomes, with 63.1% of cases achieving treatment-cured status. The previous use of SLD, history of smoking, duration of illness ≤ 1 year, extensively drug-resistant tuberculosis, and first-month sputum conversion were the variables attributed to favorable treatment outcomes observed in drug-resistant pulmonary tuberculosis cases. ROC curve analysis with AUC = 0.902, 95% CI = 0.877-0.927, and p < 0.001) has shown outstanding ability for regression model prediction for the variables influencing treatment outcomes. Conclusions: Within 2 months of treatment, most patients had converted their sputum cultures and sputum smears. The determinants of early sputum smear and sputum culture conversion, as well as favorable treatment outcomes, were identified. These factors should be considered during the design and implementation of effective strategies for drug-resistant tuberculosis control programs.

Impact of allergic rhinitis on quality of life in patients with chronic rhinosinusitis.

OBJECTIVES: To evaluate the impact of allergic rhinitis (AR) on the quality of life (QoL) in patients with chronic rhinosinusitis (CRS). METHODS: Retrospective cross-sectional study of adult patients with CRS presenting to our clinic between August 2020 and February 2023 was performed. AR was diagnosed based on a positive skin or blood allergy test. Patients' characteristics, AR status, comorbidities, endoscopy scores, and SNOT-22 scores were collected. RESULTS: A total of 514 CRS patients were included, with 265 (51.6 %) patients with AR. CRS patients with AR were younger (p = 0.004), more likely to be female (p < 0.001), and more likely to have asthma (p < 0.001). Polyp status and endoscopy scores did not differ between patients with and without AR. Baseline SNOT-22 scores were slightly worse in the AR cohort (43.6 vs 38.7, p = 0.007), which was mainly secondary to rhinologic (p = 0.002), extrarhinologic (p = 0.007), and ear/facial (p = 0.007) subdomains. Worse rhinologic and extrarhinologic scores were associated with the presence of AR after adjusting for confounding variables (Coef = 1.55, p = 0.011; and Coef = 0.83, p = 0.021 respectively). CONCLUSION: The impact of allergic rhinitis on QoL is mainly on the nasal symptoms. Further studies should look at the role of AR on the QoL of different CRS endotypes; and at the role of AR-specific treatment, such as immunotherapy, on the QoL of patients with CRS.

Bis(dimethylpyrazolyl)-aniline-s-triazine derivatives as efficient corrosion inhibitors for C-steel and computational studies.

4,6-Bis(3,5-dimethyl-1H-pyrazol-1-yl)-N-phenyl-1,3,5-triazin-2-amine (PTA-1), N-(4-bromophenyl)-4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-amine (PTA-2) and 4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-N-(4-methoxyphenyl)-1,3,5-triazin-2-amine (PTA-3) were synthesized and characterized. Their corrosion inhibition of carbon C-steel in 0.25 M H2SO4 was studied by electrochemical impedance. The inhibition efficiency (IE%) of triazine was superior due to the cumulative inhibition of triazine core structure and pyrazole motif. Potentiodynamic polarizations suggested that s-triazine derivatives behave as mixed type inhibitors. The IE% values were 96.5% and 93.4% at 120 ppm for inhibitor PTA-2 and PTA-3 bearing -Br and -OCH3 groups on aniline, respectively. While PTA-1 without an electron donating group showed only 79.0% inhibition at 175 ppm. The adsorption of triazine derivatives followed Langmuir and Frumkin models. The values of adsorption equilibrium constant K°ads and free energy change ΔG°ads revealed that adsorption of inhibitor onto steel surface was favoured. A corrosion inhibition mechanism was proposed suggesting the presence of physical and chemical interactions. Density functional theory computational investigation corroborated nicely with the experimental results. Monte Carlo simulation revealed that the energy associated with the metal/adsorbate arrangement dE ads/dN i, for both forms of PTA-2 and PTA-3 with electron donating groups (-439.73 and -436.62 kcal mol-1) is higher than that of PTA-1 molecule (-428.73 kcal mol-1). This aligned with experimental inhibition efficiency results.

Green synthesized silver nanoparticles of Terminalia bellirica leaves extract: synthesis, characterization, in-silico studies, and antimalarial activity.

Malaria is a mosquito-borne infectious disease that is caused by the Plasmodium parasite. Most of the available medication are losing their efficacy. Therefore, it is crucial to create fresh leads to combat malaria. Green silver nanoparticles (AgNPs) have recently attracted a lot of attention in biomedical research. As a result, green mediated AgNPs from leaves of Terminalia bellirica, a medicinal plant with purported antimalarial effects, were used in this investigation. Initially, cysteine-rich proteins from Plasmodium species were studied in silico as potential therapeutic targets. With docking scores between -9.93 and -11.25 kcal/mol, four leaf constituents of Terminalia bellirica were identified. The green mediated silver nanoparticles were afterward produced using leaf extract and were further examined using UV-vis spectrophotometer, DLS, Zeta potential, FTIR, XRD, and FESEM. The size of synthesized TBL-AgNPs was validated by the FESEM results; the average size of TBL-AgNPs was around 44.05 nm. The zeta potential study also supported green mediated AgNPs stability. Additionally, Plasmodium falciparum (3D7) cultures were used to assess the antimalarial efficacy, and green mediated AgNPs could effectively inhibit the parasitized red blood cells (pRBCs). In conclusion, this novel class of AgNPs may be used as a potential therapeutic replacement for the treatment of malaria.

Unsolved Controversies in Management of Infective Endocarditis.

Infective endocarditis (IE) is defined as an infection in the cardiac endothelium. It is triggered by both bacteremia and endothelial dysfunction and poses many risks to the health of the patient. Many organisms can cause IE with Staphylococcus aureus being the major cause. Signs and symptoms may vary according to age and agent but almost all cases are presented with fever, fatigue, and a maculopapular rash. Although pediatric IE is very rare, risk factors such as congenital heart defects have been identified, with some of the cases remaining a mystery. We present a case of a 19-year-old patient, previously healthy and developing subacute IE with sepsis and septic embolic showers in multiple organs. IE cannot be taken for granted as mortality is high, hence a multidisciplinary approach is prompt and necessary for the survival of the patient.

Correlation of patient reported outcome measures with endoscopic findings in pediatric chronic adenoiditis and chronic rhinosinusitis.

BACKGROUND: Studies in adult chronic rhinosinusitis (CRS) showed poor correlation between patient reported outcome measures (PROMs) and objective findings. Our goal is to study the correlation between the sinus and nasal quality of life (SN-5) and the 22-items sinonasal outcome test (SNOT-22) surveys with endoscopy findings in children with chronic adenoiditis (CA) and CRS. METHODS: Cross-sectional study of all pediatric patients (age 2-18) presenting for CA or CRS was performed. Patients and caregivers were asked to fill the SN-5 and SNOT-22 questionnaires at initial and follow up visits. Demographics and comorbidities were collected. Objective findings included endoscopy Modified Lund-Kennedy (MLK) scores and adenoid tissue size. RESULTS: 124 children were included, with mean age of 9.9 years (SD = 4.8) and 46.8% female. 36.3% had allergic rhinitis, 23.4% had asthma, and 4% had obstructive sleep apnea. Moderate correlation was found between the rhinologic domain of SNOT-22 and MLK scores (r = 0.36, p = 0.001) and between SN5 scores and adenoid size in all patients (r = 0.39, p < 0.001). SNOT-22 scores showed moderate correlation with adenoid size (r = 0.42, p < 0.001) more specifically in CA patients (r = 0.54, p < 0.001). The correlation of SN5 and MLK scores were higher in children with allergic rhinitis or asthma. The correlation between SN5 and adenoid size was lower in children with allergic rhinitis or asthma. CONCLUSION: There is discrepancy between the subjective measures and the objective findings in children with CA or CRS. The physical exam findings may not reflect the effect of CRS on the quality of life of children.

Green hydrogen generation in alkaline solution using electrodeposited Ni-Co-nano-graphene thin film cathode.

Green hydrogen generation technologies are currently the most pressing worldwide issues, offering promising alternatives to existing fossil fuels that endanger the globe with growing global warming. The current research focuses on the creation of green hydrogen in alkaline electrolytes utilizing a Ni-Co-nano-graphene thin film cathode with a low overvoltage. The recommended conditions for creating the target cathode were studied by electrodepositing a thin Ni-Co-nano-graphene film in a glycinate bath over an iron surface coated with a thin copper interlayer. Using a scanning electron microscope (SEM) and energy-dispersive X-ray (EDX) mapping analysis, the obtained electrode is physically and chemically characterized. These tests confirm that Ni, Co, and nano-graphene are homogeneously dispersed, resulting in a lower electrolysis voltage in green hydrogen generation. Tafel plots obtained to analyze electrode stability revealed that the Ni-Co-nano-graphene cathode was directed to the noble direction, with the lowest corrosion rate. The Ni-Co-nano-graphene generated was used to generate green hydrogen in a 25% KOH solution. For the production of 1 kg of green hydrogen utilizing Ni-Co-nano-graphene electrode, the electrolysis efficiency was 95.6% with a power consumption of 52 kwt h-1, whereas it was 56.212. kwt h-1 for pure nickel thin film cathode and 54. kwt h-1 for nickel cobalt thin film cathode, respectively.

Quantifying the activity profile of ASO and siRNA conjugates in glioblastoma xenograft tumors in vivo.

Glioblastoma multiforme is a universally lethal brain tumor that largely resists current surgical and drug interventions. Despite important advancements in understanding GBM biology, the invasiveness and heterogeneity of these tumors has made it challenging to develop effective therapies. Therapeutic oligonucleotides-antisense oligonucleotides and small-interfering RNAs-are chemically modified nucleic acids that can silence gene expression in the brain. However, activity of these oligonucleotides in brain tumors remains inadequately characterized. In this study, we developed a quantitative method to differentiate oligonucleotide-induced gene silencing in orthotopic GBM xenografts from gene silencing in normal brain tissue, and used this method to test the differential silencing activity of a chemically diverse panel of oligonucleotides. We show that oligonucleotides chemically optimized for pharmacological activity in normal brain tissue do not show consistent activity in GBM xenografts. We then survey multiple advanced oligonucleotide chemistries for their activity in GBM xenografts. Attaching lipid conjugates to oligonucleotides improves silencing in GBM cells across several different lipid classes. Highly hydrophobic lipid conjugates cholesterol and docosanoic acid enhance silencing but at the cost of higher neurotoxicity. Moderately hydrophobic, unsaturated fatty acid and amphiphilic lipid conjugates still improve activity without compromising safety. These oligonucleotide conjugates show promise for treating glioblastoma.

Preliminary performance study of synthetic Alumina nanoparticles for retention of cobalt and cesium cations.

In the present study, a facile nano-sized gamma alumina was synthesized and then examined for immobilization of cobalt and cesium ions individually from aqueous solutions. The comprehensive analysis of functional groups, phase composition, surface morphology and sorption characteristics of the synthesized nano-sized ϒ alumina was executed. It was deduced that acquired material was low-crystalline with a high elimination efficacy towards the concerned cations under slightly alkali and acidic conditions. Time-transient elimination scrutiny was executed and cobalt elimination rate was found relatively faster than cesium cations. Equilibrium sorption examinations confirmed that the sorption is proceeding via two diverse sites on the scavenger surface. Cobalt and cesium elimination is a spontaneous endothermic reaction of increased chaos. The attained results proved the high proficiency of the synthesized scavenger in the cations immobilization.

Role of Sinonasal Anatomic Variants in Recurrent Acute Rhinosinusitis.

OBJECTIVES: Prior studies evaluating the role of sinonasal anatomic variants with recurrent acute rhinosinusitis (RARS) are limited by inconsistent results. The goal of this study is to evaluate the association between sinonasal anatomic variants and RARS. METHODS: A 1:2 retrospective case-control study was conducted using patients presenting to the rhinology clinic from August 2020 to January 2023. A total of 60 patients with RARS were compared to 120 control patients. RARS was diagnosed based on the International Consensus Statement on Allergy and Rhinology criteria of four or more independent episodes of acute rhinosinusitis per year with at least one episode documented by objective findings, with complete resolution of the infection in-between episodes. Sinonasal anatomic variants included nasal septal deviation (NSD), concha bullosa (CB), infraorbital (Haller) cells, nasal septal spur in the middle meatus, and frontal sinus cells (supra-agger, supra-agger frontal, and suprabullar frontal cells). RESULTS: Age was similar in RARS and control patients (47.4 ± 16.5 vs. 49.3 ± 14.5, p = 0.432). Both the RARS group and control group were more likely to be female (78.3% vs. 77.5%, p = 0.899). There was no significant association between NSD and RARS compared to the control group (OR = 0.97, p = 0.916), and no significant association between any of the anatomic variants and RARS [infraorbital cells (OR = 0.64, p = 0.167), CB (OR = 0.84, p = 0.596), spur in the middle meatus (OR = 1.28, p = 0.514), supra-agger (OR = 0.88, p = 0.708), supra-agger frontal cells (OR = 0.97, p = 0.939), or suprabullar frontal cells (OR = 1.13, p = 0.766)]. CONCLUSION: Our findings suggest no association between nasal septal deviation or any of the anatomic variants studied and RARS. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Petrographical and petrophysical rock typing for flow unit identification and permeability prediction in lower cretaceous reservoir AEB_IIIG, Western Desert, Egypt.

The primary objective of this study is to identify and analyze the petrophysical properties of the newly investigated AEB_IIIG member reservoir in Meleiha West Deep (MWD) Field and to classify it into different rock types. Additionally, this research intends to develop mathematical equations that may be utilized to estimate permeability in uncored sections of the same well or in other wells where core samples are unavailable. The analysis focused on the pore hole records of ten wells that were drilled in MWD Field. The reservoir levels were identified, and their petrophysical parameters were evaluated using well logs and core data. We were able to recognize seven different types of rocks (petrophysical static rock type 1 (PSRT1) to PSRT7) using petrography data, the reservoir quality index (RQI), the flow zone index (FZI), R35, hydraulic flow units (HFUs), and stratigraphy modified Lorenz (SML) plots. The analysis of the petrophysical data shows that AEB_IIIG has unsteady net pay thicknesses over the area. It has a range of 8-25% shale volume, 12-17% effective porosity, and 72-92% hydrocarbon saturation. The RQI results show that psrt1, psrt2 and psrt3 have a good reservoir quality as indicated by high R35 and helium porosity, respectively. They contribute with more than 75% of the reservoir production. The equation derived for each rock type of AEB_IIIG reservoir can be employed to forecast the permeability value distribution inside the reservoir.

Sakuranetin ameliorates streptozotocin-induced diabetes in rodents by inhibiting caspase-3 activity, modulating hematological parameters, and suppressing inflammatory cytokines: a molecular docking and dynamics study.

Diabetes affects people of all ages, regardless of gender and background. To date, there is no evidence for the effect of sakuranetin against the streptozotocin (STZ)-induced diabetes paradigm. The research was directed to evaluate the antidiabetic activity of sakuranetin in the STZ model invoking the diabetes-induced disease paradigm. STZ (I.P. 60 mg/kg) is directed to induce type 2 diabetes in experimental rats. Recent research pursued to regulate the anti-diabetic ability of sakuranetin at both 10 and 20 mg/kg in STZ-induced rats. Furthermore, molecular docking research was implemented to evaluate sakuranetin requisite attraction to inflammatory indicators. Various anti-diabetic [(glucose, hemoglobin A1c (HbA1c), and insulin)], lipid profile [triglycerides (TG), total cholesterol (TC), and high-density lipoproteins (HDL)], hematological parameters [Hemoglobin (HGB), packed cell volume (PCV), red blood cells (RBC), mean corpuscular volume (MCV), platelet (PLT), and white blood cells (WBC), pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)], antioxidant level [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH)], lipid oxidation, and caspase-3 were evaluated. Furthermore, molecular docking and dynamics were performed for TNF-α (2AZ5), IL-6 (1ALU), IL-1ß (6Y8M), Caspase-3 (1NME) and serum insulin (4IBM) target ligands. Sakuranetin treatment at both doses restored the biochemical parameters i.e. blood glucose, insulin, HbA1c, lipid profile, hematological parameters, pro-inflammatory markers, antioxidant levels, lipid oxidation, and caspase-3 in the context of diabetic rats. It also showed favorable binding affinity on inflammatory markers. Sakuranetin binds to proteins 2AZ5, 1ALU, 6Y8M, 1NME, and 4IBM at -7.489, -6.381, -6.742, -7.202, and -8.166 Kcal/mol, respectively. All of the findings from the molecular dynamics simulations points toward a considerable change in the conformational dynamics of protein upon binding with sakuranetin. The potential use of sakuranetin as an alternative diabetes medication will aid future research as a potent anti-diabetic agent.Communicated by Ramaswamy H. Sarma.

New record of Philometra species from the marine edible fish Terapon jarbua collected from the Sindh, Arabian Sea, Pakistan.

Diseases in fish due to helminth parasites, especially Philometra species, are the primary worry in aquaculture. Philometra are responsible for health problem in fishes they directly affect fish growth and population parameters. A comprehensive survey was conducted involving the examination of the marine fish species Terapon jarbua, gathered from the coastal waters of Sindh, Pakistan In this research different Philometra species from marine fish Terapon jarbua during 2021 and 2022. Philometra nematodes, belonging to the family Philometridae, are common parasitic organisms inhabiting both marine and freshwater environments. Their prevalence, particularly when existing in high numbers within host organisms, can lead to severe and potentially lethal consequences. Employing light microscopy techniques, diverse species of Philometra were identified, including Philometra teraponi, P. jarbuai, P. arabiai, P. karachii, and P. awarii, localized primarily within the ovaries of the host fish. A total of 140 fish samples were examined and 76 were infected. The intensity of infected fish was 54.28%. The identification process encompassed meticulous analysis of crucial parameters, such as body size, esophagus length, positioning of the nerve ring, dimensions of the ventriculus, and ligament size. Intriguingly, the parasites were found in varying contexts; while some were free within the ovaries, others were embedded within tissues, inducing severe muscular dystrophy. This research presents novel findings of Philometra nematodes in the marine waters of Pakistan, extending their host and geographical distribution records. Future studies are needed to better evaluate and describe the dynamics and the epidemiology of Philometra infection in wild and cultured fish species.

Harnessing the supremacy of MEG3 LncRNA to defeat gastrointestinal malignancies.

Evidence suggests that long non-coding RNAs (lncRNAs) play a pivotal role in the carcinogenesis and progression of various human malignancies including gastrointestinal malignancies. This comprehensive review reports the functions and mechanisms of the lncRNA maternally expressed gene 3 (MEG3) involved in gastrointestinal malignancies. It summarizes its roles in mediating the regulation of cellular proliferation, apoptosis, migration, invasiveness, epithelial-to-mesenchymal transition, and drug resistance in several gastrointestinal cancers such as colorectal cancer, gall bladder cancer, pancreatic cancer, gastric cancer, esophageal cancer, cholangiocarcinoma, gastrointestinal stromal tumors and most importantly, hepatocellular carcinoma. In addition, the authors briefly highlight its implicated mechanistic role and interactions with different non-coding RNAs and oncogenic signaling cascades. This review presents the rationale for developing non coding RNA-based anticancer therapy via harnessing the power of MEG3 in gastrointestinal malignancies.

Structure-based multitargeted docking screening, pharmacokinetics, DFT, and dynamics simulation studies reveal mitoglitazone as a potent inhibitor of cellular survival and stress response proteins of lung cancer.

Lung cancer is a disease in which lung cells grow abnormally and uncontrollably, and the cause of it is direct smoking, secondhand smoke, radon, asbestos, and certain chemicals. The worldwide leading cause of death is lung cancer, which is responsible for more than 1.8 million deaths yearly and is expected to rise to 2.2 million by 2030. The most common type of lung cancer is non-small cell lung cancer (NSCLC), which accounts for about 80% and small cell lung cancer (SCLC), which is more aggressive than NSCLC and is often diagnosed later and accounts for 20% of cases. The global concern for lung cancer demands efficient drugs with the slightest chance of developing resistance, and the idea of multitargeted drug designing came up with the solution. In this study, we have performed multitargeted molecular docking studies of Drug Bank compounds with HTVS, SP and XP algorithms followed by MM\GBSA against the four proteins of lung cancer cellular survival and stress responses, which revealed Mitoglitazone as a multitargeted inhibitor with a docking and MM\GBSA score ranging from - 5.784 to - 7.739 kcal/mol and - 25.81 to - 47.65kcal/mol, respectively. Moreover, we performed pharmacokinetics studies and QM-based DFT analysis, showing suitable candidate and interaction pattern analysis revealed the most count of interacting residues was 4GLY, 5PHE, 6ASP, 6GLU, 6LYS, and 6THR. Further, the results were validated with SPC water model-based MD simulation for 100ns in neutralised condition, showing the cumulative deviation and fluctuation < 2Å with many intermolecular interactions. The whole analysis has suggested that Mitoglitazone can be used as a multitargeted inhibitor against lung cancer-however, experimental studies are needed before human use.

Nucleic Acid Therapeutics: Successes, Milestones, and Upcoming Innovation.

Nucleic acid-based therapies have become the third major drug class after small molecules and antibodies. The role of nucleic acid-based therapies has been strengthened by recent regulatory approvals and tremendous clinical success. In this review, we look at the major obstacles that have hindered the field, the historical milestones that have been achieved, and what is yet to be resolved and anticipated soon. This review provides a view of the key innovations that are expanding nucleic acid capabilities, setting the stage for the future of nucleic acid therapeutics.

A review on mechanistic insights into structure and function of dystrophin protein in pathophysiology and therapeutic targeting of Duchenne muscular dystrophy.

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive genetic disorder characterized by progressive and severe muscle weakening and degeneration. Among the various forms of muscular dystrophy, it stands out as one of the most common and impactful, predominantly affecting boys. The condition arises due to mutations in the dystrophin gene, a key player in maintaining the structure and function of muscle fibers. The manuscript explores the structural features of dystrophin protein and their pivotal roles in DMD. We present an in-depth analysis of promising therapeutic approaches targeting dystrophin and their implications for the therapeutic management of DMD. Several therapies aiming to restore dystrophin protein or address secondary pathology have obtained regulatory approval, and many others are ongoing clinical development. Notably, recent advancements in genetic approaches have demonstrated the potential to restore partially functional dystrophin forms. The review also provides a comprehensive overview of the status of clinical trials for major therapeutic genetic approaches for DMD. In addition, we have summarized the ongoing therapeutic approaches and advanced mechanisms of action for dystrophin restoration and the challenges associated with DMD therapeutics.

Multispecies-targeting siRNAs for the modulation of JAK1 in the skin.

Identifying therapeutic oligonucleotides that are cross-reactive to experimental animal species can dramatically accelerate the process of preclinical development and clinical translation. Here, we identify fully chemically-modified small interfering RNAs (siRNAs) that are cross-reactive to Janus kinase 1 (JAK1) in humans and a large variety of other species. We validated the identified siRNAs in silencing JAK1 in cell lines and skin tissues of multiple species. JAK1 is one of the four members of the JAK family of tyrosine kinases that mediate the signaling transduction of many inflammatory cytokine pathways. Dysregulation of these pathways is often involved in the pathogenesis of various immune disorders, and modulation of JAK family enzymes is an effective strategy in the clinic. Thus, this work may open up unprecedented opportunities for evaluating the modulation of JAK1 in many animal models of human inflammatory skin diseases. Further chemical engineering of the optimized JAK1 siRNAs may expand the utility of these compounds for treating immune disorders in additional tissues.

Exploring the promising potential of noscapine for cancer and neurodegenerative disease therapy through inhibition of integrin-linked kinase-1.

Integrin-linked kinase (ILK), a ß1-integrin cytoplasmic domain interacting protein, supports multi-protein complex formation. ILK-1 is involved in neurodegenerative diseases by promoting neuro-inflammation. On the other hand, its overexpression induces epithelial-mesenchymal transition (EMT), which is a major hallmark of cancer and activates various factors associated with a tumorigenic phenotype. Thus, ILK-1 is considered as an attractive therapeutic target. We investigated the binding affinity and ILK-1 inhibitory potential of noscapine (NP) using spectroscopic and docking approaches followed by enzyme inhibition activity. A strong binding affinity of NP was measured for the ILK-1 with estimated Ksv (M-1) values of 1.9 × 105, 3.6 × 105, and 4.0 × 105 and ∆G0 values (kcal/mol) -6.19554, -7.8557 and -8.51976 at 298 K, 303 K, and 305 K, respectively. NP binds to ILK-1 with a docking score of -6.6 kcal/mol and forms strong interactions with active-site pocket residues (Lys220, Arg323, and Asp339). The binding constant for the interaction of NP to ILK-1 was 1.04 × 105 M-1, suggesting strong affinity and excellent ILK-1 inhibitory potential (IC50 of ∼5.23µM). Conformational dynamics of ILK-1 were also studied in the presence of NP. We propose that NP presumably inhibits ILK-1-mediated phosphorylation of various downstream signalling pathways that are involved in cancer cell survival and neuroinflammation.

Gender Differences in Adults With Chronic Rhinosinusitis: A Scoping Review.

OBJECTIVE: Gender differences in chronic rhinosinusitis (CRS) have been demonstrated in many studies over the last 15 years. The purpose of this scoping review is to investigate the current knowledge on gender differences in CRS and to analyze the gaps in the literature. DATA SOURCES: A systematic search of PubMed, Cochrane Library, and Embase databases was performed. REVIEW METHODS: This scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Studies that evaluated gender differences in CRS were included in the review. RESULTS: Of the 523 abstracts reviewed, a total of 23 studies met the criteria for inclusion. Articles consisted of retrospective and prospective cohort studies. They were divided into 3 categories based on whether they evaluated gender differences in (1) presentation and baseline quality of life, (2) pathophysiology, and/or (3) outcomes of treatment. Eleven studies addressed differences in presentation, 5 addressed differences in pathophysiology, and 10 dealt with differences in outcomes after surgical or medical management. Most of the studies showed worse baseline QoL secondary to CRS in women, with outcome of treatment being similar in both genders. CONCLUSION: The experience of CRS appears to vary between genders, with women experiencing a greater subjective burden of disease than men, though with similar outcomes after treatment. Further research is indicated, particularly involving the pathophysiology of CRS, to fully understand the underlying causes of these discrepancies.