The complement system provides host defense against pathogens and environmental stress. C3, the central component of complement, is present in the blood and increases in the bronchoalveolar lavage fluid following injury. We recently discovered that C3 is taken up by certain cell types and cleaved intracellularly to C3a and C3b. C3a is required for CD4+T cell survival. These observations made us question if complement operates at environmental interfaces, particularly in the respiratory tract. We found that airway epithelial cells [AECs, represented by both primary human tracheobronchial cells (hTECs) and BEAS-2B (cell line)] cultured in C3-free media were unique from other cell types in that they contained large intracellular stores of de novo synthesized C3. A fraction of this protein reduced ("storage form") while the remainder did not, consistent with it being pro-C3 ("precursor form"). These two forms of intracellular C3 were absent in CRISPR knockout-induced C3-deficient AECs and decreased using C3 siRNA, indicating endogenous generation. Proinflammatory cytokine exposure increased both stored and secreted forms of C3. Further, AECs took up C3 from exogenous sources, which mitigated stress-associated cell death (e.g., oxidative stress, starvation). C3 stores were notably increased within AECs in lung tissues from individuals with different end-stage lung diseases. Thus, at-risk cells furnish C3 through biosynthesis and/or uptake to increase locally available C3 during inflammation, while intracellularly, these stores protect against certain inducers of cell death. These results establish the relevance of intracellular C3 to airway epithelial biology and suggest novel pathways for complement-mediated host protection in the airway.
Introduction:In malaria-stricken regions, malaria continues to be one of the primary causes of mortality for children. The number of malaria-related fatalities has drastically decreased because of artemisinin-based pharmacological regimens. Methods: Two independent researchers did a comprehensive literature search using PubMed/MEDLINE and Google Scholar from its inception to September 2022.Results: After evaluating RTS, S/AS01 for its safety, effectiveness, and feasibility, the European Medicines Agency (EMA) issued a favorable conclusion. It was suggested that the RTS, S malaria vaccine be used extensively by the World Health Organization on October 6, 2021. The successful pilot program testing the malaria vaccine in Ghana, Kenya, and Malawi served as the basis for this proposal. Conclusion: Several challenges need to be addressed to ensure the success of vaccination programs. From the acceptability perspective, issues such as inadequate community engagement, concerns about side effects, and issues with the delivery and quality of healthcare services can affect the acceptance of the vaccine. From the feasibility standpoint, factors such as lack of transportation or long distances to healthcare facilities and the perception of completion of the vaccination calendar can affect the feasibility of the vaccine. Lastly, the availability of the vaccine is also a major concern as it may not be readily available to meet the demands.
Vitiligo is a multifaceted autoimmune depigmenting disorder affecting around 0.5 to 2.0% of individuals globally. Standardizing diagnosis and therapy tracking can be arduous, as numerous clinical evaluation methods are subject to interobserver variability and may not be validated. Therefore, there is a need for diagnostic tools that are objective, dependable, and preferably non-invasive.AimsThis systematic review provides a comprehensive overview of the non-invasive objective skin measurement methods that are currently used to evaluate the diagnosis, severity, and progression of vitiligo, as well as the advantages and limitations of each technique.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was used for the systematic review. Scopus, Embase, Cochrane Library, and Web of Science databases were comprehensively searched for non-invasive imaging and biophysical skin measuring methods to diagnose, evaluate the severity of, or monitor the effects of vitiligo treatment. The risk of bias in included articles was assessed using the QUADAS-2 quality assessment scale.ResultsAn extensive literature search resulted in 64 studies for analysis, describing eight imaging techniques (reflectance confocal microscopy, computer-aided imaging analysis, optical coherence tomography, infrared photography, third-harmonic generation microscopy, multiphoton microscopy, ultraviolet light photography, and visible light/digital photograph), and three biophysical approaches (dermoscopy, colorimetry, spectrometry) used in diagnosing and assessing vitiligo. Pertinent information about functionality, mechanisms of action, sensitivity, and specificity was obtained for all studies, and insights into the strengths and limitations of each diagnostic technique were addressed. Methodological study quality was adequate; however, statistical analysis was not achievable because of the variety of methods evaluated and the non-standardized reporting of diagnostic accuracy results.ConclusionsThe results of this systematic review can enhance clinical practice and research by providing a comprehensive overview of the spectrum of non-invasive imaging and biophysical techniques in vitiligo assessment. Studies with larger sample sizes and sound methodology are required to develop verified methods for use in future practice and research.Systematic review registration(PROSPERO) database, (CRD42023395996).
Review question / Objective: To test the effectiveness of multimodality therapy using minoxidil and micmroneedling, in comparison to minoxodil alone for the treatment of alopecia. In terms of the PICO framework: Population: Includes patients with any form of clinically diagnosed alopecia. Intervention: Includes using combination therapy with microneedling and minoxidil in the treatment of alopecia. Comparison: Includes comparison to minoxidil alone as control group. Outcome: Primary outcome: Increased hair density. Secondary outcome: Increased hair diameter. Condition being studied: Alopecia (hair loss) is a condition that is frequently seen in dermatology. When a thorough examination is made, the root of the issue is frequently revealed, allowing for an explanation and the most suitable treatments. Nevertheless, hair loss can occasionally be the first indicator of a serious underlying medical problem, be observed in conjunction with other conditions, or be a side effect of treatment. Furthermore, alopecia may result in distressingly noticeable symptoms, cause significant patient distress, and cause alopecia with lifelong scars and irreversible hair loss. Therefore, with these illnesses, a precise diagnosis and quick therapy are essential for the most beneficial outcomes.
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