Zinc finger protein 263 upregulates interleukin 33 and suppresses autophagy to accelerate the malignant progression of non-small cell lung cancer / La proteína 263 con dedos de zinc regula positivamente la interleucina 33 y suprime la autofagia para acelerar la progresión maligna del cáncer de pulmón de células no pequeñas

Purpose: Non-small cell lung cancer (NSCLC) is a complex disease that remains a major public health concern worldwide. One promising avenue for NSCLC treatment is the targeting of transcription factors that regulate key pathways involved in cancer progression. In this study, we investigated the role of the transcription factor ZNF263 in NSCLC and its impact on the regulation of IL33, apoptosis, and autophagy. Methods: Levels of ZNF263 in tissues and cell lines were identified, after which the effects of its knockdown on cellular malignant behaviors, apoptosis and autophagy were assessed. Based on bioinformatics analysis, ZNF263 was found to bind to IL33 promoter, their mutual relationship was confirmed, as well as the role of IL33 in the regulation of ZNF263. The involvement of ZNF263 in the growth of xenograft tumors was assessed using tumor-bearing nude mouse models. Results: Experimental results revealed that ZNF263 was upregulated in NSCLC tissue samples and cell lines. Its expression level is positively correlated with cellular malignant behaviors. We further demonstrated that ZNF263 upregulated IL33 expression, which, in turn, promoted the proliferation and migration, inhibited apoptosis and autophagy in NSCLC cells. Furthermore, ZNF263 knockdown reduced the growth of xenograft tumors in nude mice. Conclusion: This finding suggests that the inhibition of ZNF263 or IL33 may represent a novel therapeutic strategy for NSCLC. Importantly, our results highlight the crucial role of transcription factors in NSCLC and their potential as therapeutic targets.(AU)

The role of CXCL10 as a biomarker for immunological response among patients with leprosy: a systematic literature review.

Introduction: Involvement of a chemokine known as C-X-C motif chemokine ligand 10 or CXCL10 in the immunopathology of leprosy has emerged as a possible immunological marker for leprosy diagnosis and needed to be investigate further. The purpose of this systematic review is to assess CXCL10's potential utility as a leprosy diagnostic tool and evaluation of therapy. Methods: This systematic review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. A thorough search was carried out to find relevant studies only in English and limited in humans published up until September 2023 using PubMed, Scopus, Science Direct, and Wiley Online Library database with keywords based on medical subject headings (MeSH) and no exclusion criteria. The Newcastle-Ottawa Scale (NOS) was utilized for quality assessment, while the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) was utilized for assessing the risk of bias. Additionally, a narrative synthesis was conducted to provide a comprehensive review of the results. Results: We collected a total of 115 studies using defined keywords and 82 studies were eliminated after titles and abstracts were screened. We assessed the eligibility of the remaining 26 reports in full text and excluded four studies due to inappropriate study design and two studies with incomplete outcome data. There were twenty included studies in total with total of 2.525 samples. The included studies received NOS quality evaluation scores ranging from 6 to 8. The majority of items in the risk bias assessment, using RoBANS, across all included studies yielded low scores. However, certain items related to the selection of participants and confounding variables showed variations. Most of studies indicate that CXCL10 may be a helpful immunological marker for leprosy diagnosis, particularly in leprosy reactions as stated in seven studies. The results are better when paired with other immunological markers. Its effectiveness in field-friendly diagnostic tools makes it one of the potential biomarkers used in diagnosing leprosy patients. Additionally, CXCL10 may be utilized to assess the efficacy of multidrug therapy (MDT) in leprosy patients as stated in three studies. Conclusion: The results presented in this systematic review supports the importance of CXCL10 in leprosy diagnosis, particularly in leprosy responses and in tracking the efficacy of MDT therapy. Using CXCL10 in clinical settings might help with leprosy early diagnosis. Yet the findings are heterogenous, thus more investigation is required to determine the roles of CXCL10 in leprosy while taking into account for additional confounding variables.

Target product profiles: leprosy diagnostics.

The World Health Organization (WHO) aims to reduce new leprosy cases by 70% by 2030, necessitating advancements in leprosy diagnostics. Here we discuss the development of two WHO's target product profiles for such diagnostics. These profiles define criteria for product use, design, performance, configuration and distribution, with a focus on accessibility and affordability. The first target product profile outlines requirements for tests to confirm diagnosis of leprosy in individuals with clinical signs and symptoms, to guide multidrug treatment initiation. The second target product profile outlines requirements for tests to detect Mycobacterium leprae or M. lepromatosis infection among asymptomatic contacts of leprosy patients, aiding prophylactic interventions and prevention. Statistical modelling was used to assess sensitivity and specificity requirements for these diagnostic tests. The paper highlights challenges in achieving high specificity, given the varying endemicity of M. leprae, and identifying target analytes with robust performance across leprosy phenotypes. We conclude that diagnostics with appropriate product design and performance characteristics are crucial for early detection and preventive intervention, advocating for the transition from leprosy management to prevention.

L'Organisation mondiale de la Santé (OMS) vise à réduire le nombre de nouveaux cas de lèpre de 70% d'ici 2030, ce qui nécessite un meilleur diagnostic de la maladie. Dans le présent document, nous évoquons le développement de deux profils de produit cible établis par l'OMS à cette fin. Ces profils définissent des critères en matière d'utilisation, de conception, de performances, de configuration et de distribution du produit, en accordant une attention particulière à l'accessibilité et à l'abordabilité. Le premier profil de produit cible décrit les exigences pour les tests servant à confirmer le diagnostic de la lèpre chez les individus qui présentent des signes cliniques et des symptômes, afin d'orienter l'instauration d'un traitement à base de plusieurs médicaments. Le second profil de produit cible décrit les exigences pour les tests servant à détecter une infection à Mycobacterium leprae ou M. lepromatosis parmi les contacts asymptomatiques de patients lépreux, ce qui contribue à l'adoption de mesures prophylactiques et à la prévention. Nous avons eu recours à une modélisation statistique pour évaluer les exigences de sensibilité et de spécificité de ces tests diagnostiques. Cet article met en évidence les obstacles à l'atteinte d'un niveau élevé de spécificité en raison de l'endémicité variable de M. leprae, et à l'identification d'analytes cibles offrant de bons résultats chez les phénotypes lépreux. Nous concluons qu'un diagnostic reposant sur des caractéristiques de performance et de conception appropriées est essentiel pour détecter rapidement la maladie et intervenir en amont, et nous plaidons pour une prévention plutôt qu'une gestion de la lèpre.

La Organización Mundial de la Salud (OMS) pretende reducir los nuevos casos de lepra en un 70% para 2030, lo que requiere avances en el diagnóstico de la lepra. Aquí se analiza el desarrollo de dos perfiles de productos objetivo de la OMS para este tipo de diagnósticos. Estos perfiles definen los criterios de uso, diseño, rendimiento, configuración y distribución de los productos, centrándose en su accesibilidad y asequibilidad. El primer perfil de producto objetivo describe los requisitos de las pruebas para confirmar el diagnóstico de la lepra en personas con signos y síntomas clínicos, con el fin de orientar el inicio del tratamiento con múltiples fármacos. El segundo perfil de producto objetivo describe los requisitos de las pruebas para detectar la infección por Mycobacterium leprae o M. lepromatosis entre los contactos asintomáticos de los pacientes con lepra, para facilitar las intervenciones profilácticas y la prevención. Se utilizaron modelos estadísticos para evaluar los requisitos de sensibilidad y especificidad de estas pruebas diagnósticas. El artículo destaca las dificultades para lograr una alta especificidad, dada la diferente endemicidad de M. leprae, y para identificar analitos diana con un rendimiento sólido en todos los fenotipos de lepra. Concluimos que los diagnósticos con un diseño de producto y unas características de rendimiento adecuados son fundamentales para la detección precoz y la intervención preventiva, lo que favorece la transición del manejo de la lepra a la prevención.

Statistical optimized production of Phytase from Hanseniaspora guilliermondii S1 and studies on purification, homology modelling and growth promotion effect.

This investigation was performed to obtain a promising phytase enzyme producing yeast. In this regard, the PSM was used to isolate the phytase-producing Hanseniaspora guilliermondii S1 (MG663578) from sugarcane juice. The SSF optimum conditions for phytase generation were optimized using (OVAT) one-variable-at-a-time strategy using both Box-Behnken design and shake flask method (g/100 ml: 0.05 yeast extract, 0.15 Peptone, 0.05 malt extract 0.50 dextrose, pH 5.8 and 28ᵒC). The protein model developed was shown to be adequate for phytase production (91% accuracy), with the greatest phytase productivity in shake flask with substrate jack fruit seed powder being 395 ± 0.43 U/ml compared to 365U/ml for the BBD projected value. Crude Phytase was partially purified with a protein recovery of 43%, revealing a molecular weight of 120 kDa. It had an enzyme kinetic value of Km 3.3 mM and a Vmax of 19.1 mol/min. The 3D structure of PhyS1 amino acid sequences (PhyS1. B99990002) was simulated using Modeler 9.23, and the validated result revealed that 86.7% were in the favored region by Ramachandran plot. The SAVES server verified the 3D PDB file as satisfactory, and the model (in.pdb format) was uploaded in the PMDB database with the accession number ID: PM0082974. At the lab level, Hanseniaspora guilliermondii S1 (MG663578) producing phytase exhibited successful plant growth promotion activity in Ragi - CO 19 (Eleusine coracana L.) and Rice -Navarai - IR 64 (Oryza sativa L.). As a result, a phytase-based formulation for sustainable agriculture must be developed and tested on a large scale in diverse geographical areas of agricultural lands to determine its effect and potential on plant development.

Phylogeny and Taxonomic Revision of the Genus Melanosciadium (Apiaceae), Based on Plastid Genomes and Morphological Evidence.

Melanosciadium is considered a monotypic genus and is also endemic to the southwest of China. No detailed phylogenetic studies or plastid genomes have been identified in Melanosciadium. In this study, the plastid genome sequence and nrDNA sequence were used for the phylogenetic analysis of Melanosciadium and its related groups. Angelica tsinlingensis was previously considered a synonym of Hansenia forbesii. Similarly, Ligusticum angelicifolium was previously thought to be the genus Angelica or Ligusticopsis. Through field observations and morphological evidence, we believe that the two species are more similar to M. pimpinelloideum in leaves, umbel rays, and fruits. Meanwhile, we found a new species from Anhui Province (eastern China) that is similar to M. pimpinelloideum and have named it M. Jinzhaiensis. We sequenced and assembled the complete plastid genomes of these species and another three Angelica species. The genome comparison results show that M. pimpinelloideum, A. tsinlingensis, Ligusticum angelicifolium, and M. jinzhaiensis have similarities to each other in the plastid genome size, gene number, and length of the LSC and IR regions; the plastid genomes of these species are distinct from those of the Angelica species. In addition, we reconstruct the phylogenetic relationships using both plastid genome sequences and nrDNA sequences. The phylogenetic analysis revealed that A. tsinlingensis, M. pimpinelloideum, L. angelicifolium, and M. jinzhaiensis are closely related to each other and form a monophyletic group with strong support within the Selineae clade. Consequently, A. tsinlingensis and L. angelicifolium should be classified as members of the genus Melanosciadium, and suitable taxonomical treatments have been proposed. Meanwhile, a comprehensive description of the new species, M. jinzhaiensis, is presented, encompassing its habitat environment and detailed morphological traits.

Improving the Monophenolic Yield of Lignin Depolymerization in Dualistic Aprotic Solvent System by Organic Solvent Fractionation.

Converting lignin into aromatic chemicals is a promising strategy for the high-value utilization of lignocellulosic feedstock. However, the inherent heterogeneity of lignin poses a significant obstacle to achieving efficient conversion and optimal product yields within bio-refinery systems. Herein, we employed a one-step fractionation method to enhance lignin homogeneity and utilized the THF/DMSO-EtONa (tetrahydrofuran/dimethyl sulfoxide-sodium ethoxide) system to depolymerize the fractionated lignin. Three protic and three aprotic solvents were used for fractionation. The impact of the solvent properties on the structure and the depolymerization efficiency of the fractionated lignin was investigated. Methanol-fractionated lignin generated the benzoic acid compounds with a yield of 30 wt%, 50 % higher than that of the unfractionated lignin. The polarities (δP), hydrogen bonding abilities (δH), and viscosities (η) of selected protic solvents showed strong linear correlation with molecular weight (Mw), polymer dispersity index (PDI), and syringyl/guaiacyl ratio (S/G ratio) of the fractionated lignin, as well as the total yield of benzoic acid compounds derived from the ß-O-4 bond cleavage. This study elucidates the relationship between solvent properties and lignin structure and proposes a promising approach for refining lignin to enhance utilization efficiency, thereby presenting a potential strategy for value-added application of complex lignin polymers.

Evaluating Stromal Vascular Fraction As a Treatment for Peripheral Nerve Regeneration: A Scoping Review.

PURPOSE: This study aims to investigate the potential of stromal vascular fraction (SVF) for peripheral nerve regeneration. METHODS: A scoping review of Scopus and PubMed databases was conducted. Inclusion criteria were human or animal studies exploring the use of SVF for peripheral nerve regeneration. Studies were categorized by assessed outcomes: pain assessment, neural integrity, muscle recovery, and functional recovery. Level of evidence and study quality were assessed. RESULTS: Nine studies met the inclusion criteria. SVF injection in humans with trigeminal neuropathic pain reduced pain scores from 7.5 ± 1.58 to 4.3 ± 3.28. SVF injection improved sensation in humans with leprosy neuropathy. Repairing transected rat sciatic nerves with SVF-coated nerve autografts improved wet muscle weight ratios (0.65 ± 0.11 vs 0.55 ± 0.06) and sciatic functional index (SFI) scores (-68.2 ± 9.2 vs -72.5 ± 8.9). Repairing transected rat sciatic nerves with SVF-coated conduits increased the ratio of gastrocnemius muscle weights (RGMW) (7-10% improvement), myelinated fibers (1,605 ± 806.2 vs 543.6 ± 478.66), and myelin thickness (5-20% increase). Repairing transected rat facial nerves with SVF-coated conduits improved whisker motion (9.22° ± 0.65° vs 1.90° ± 0.84°) and myelin thickness (0.57 µm ± 0.17 vs 0.45 µm ± 0.14 µm). Repairing transected rat sciatic nerves with SVF-coated nerve allografts improved RGMW (85 vs 50%), SFI scores (-20 to -10 vs -40 to -30), and Basso, Beatie, and Bresnahan locomotor scores (18 vs 15). All metrics mentioned above were statistically significant. The human studies were level 4 evidence due to being case series, while animal studies were the lowest level of evidence. CONCLUSION: Despite initial promising results, the low-level evidence from the included studies warrants further investigation.

[Chronic communicable and non-communicable pathology and skin pathology of the migrant patient]. / Enfermedad crónica transmisible y no transmisible, y enfermedad cutánea del paciente migrante.

The care of migrant patients includes initial screening and lifelong monitoring, highlighting the importance of preventing and tracking chronic, communicable and non-communicable diseases. The prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity varies by ethnicity, influenced by genetic factors, lifestyle, and socio-economic status. Preventive measures, health promotion, and risk factor identification are crucial. Chronic communicable diseases may manifest years after transmission, underscoring the necessity of primary care screening, especially for populations from endemic or high-risk areas. Imported skin lesions are a common reason for consultation among migrant and traveller patients. Their ethiology is varied, ranging from common conditions such as scabies, mycoses, and urticaria to tropical dermatoses like filariasis and leprosy.

Serodiagnosis of paucibacillary and multibacillary leprosy using a recombinant chimeric protein composed of specific B-cell epitopes derived from Mycobacterium leprae proteins.

Leprosy diagnosis is difficult due to the clinical similarity with other infectious diseases, and laboratory tests presents problems related to sensitivity and/or specificity. In this study, we used bioinformatics to assess Mycobacterium leprae proteins and formulated a chimeric protein that was tested as a diagnostic marker for the disease. The amino acid sequences from ML0008, ML0126, ML0308, ML1057, ML2028, ML2038, ML2498 proteins were evaluated, and the B-cell epitopes QASVAYPATSYADFRAHNHWWNGP, SLQRSISPNSYNTARVDP and QLLGQTADVAGAAKSGPVQPMGDRGSVSPVGQ were considered M. leprae-specific and used to construct the gene encoding the recombinant antigen. The gene was constructed, the recombinant protein was expressed, purified and tested in ELISA using 252 sera, which contained samples from multibacillary (MB) or paucibacillary (PB) leprosy patients, from their household contacts and healthy individuals, as well as from patients with Chagas disease, visceral and tegumentary leishmaniases (VL/TL), malaria, tuberculosis, and HIV. Sensitivity (Se) and specificity (Sp) for MB and PB samples compared to sera from both healthy subjects and individuals with cross-reactive diseases were 100%. The Se value for MB and PB samples compared to sera from household contacts was 100%, but Sp was 64%. In conclusion, data suggest that this protein could be considered in future studies for leprosy diagnosis.

Genetic diversity of Mycobacterium leprae: Need to move towards genome-wide approaches.

ABSTRACT: Leprosy, an ancient disease, continues to be a public health concern as it remains endemic in several countries. After reaching the elimination target (1/10,000) as a public health problem in 2005 in India, around 1.2 lakh cases have been detected every year over the last decade indicating active transmission of leprosy bacillus (Mycobacterium leprae). Single-nucleotide polymorphisms (SNPs), genomic insertions/deletions and variable-number tandem repeats (VNTRs) have been identified as genetic markers for tracking M. leprae transmission. As the leprosy bacilli cannot be cultured in vitro, molecular testing of M. leprae genotypes is done by polymerase chain reaction-based sequencing which provides a practical alternative for the identification of strains as well as drug resistance-associated mutations. Whole-genome sequencing (WGS) of M. leprae directly from clinical samples has also proven to be an effective tool for identifying genetic variations which can further help refine the molecular epidemiological schemes based on SNPs and VNTRs. However, the WGS data of M. leprae strains from India are scarce, being responsible for a gross under-representation of the genetic diversity of M. leprae strains present in India and need to be addressed suitably. Molecular studies of leprosy can provide better insight into phylogeographic markers to monitor the transmission dynamics and emergence of antimicrobial resistance. An improved understanding of M. leprae transmission is essential to guide efficient leprosy control strategies. Therefore, this review compiles and discusses the current status of molecular epidemiology, genotyping and the potential of genome-wide analysis of M. leprae strains in the Indian context.