A document by Divya Sharma. Click on the document to view its contents.

Vemurafenib, one of the selective BRAF inhibitor, is less effective in BRAF-mutant thyroid cancer, including anaplastic thyroid cancer (ATC), the mechanisms of which are still lacking. Pseudopodium-enriched atypical kinase 1 (PEAK1) has been demonstrated to be upregulated in human malignancies. Enhanced PEAK1 expression facilitates tumor cell survival and chemoresistance. Here we investigated the role and mechanisms of targeting PEAK1 in reversing vemurafenib resistance in ATC 8505C cells. PEAK1 depletion alone promotes cell cycle arrest, but not affect cell apoptosis.PEAK1 depletion sensitized 8505C cells to vemurafenib by promoting cell cycle arrest and inducing cell apoptosis. Vemurafenib could quickly inhibit ERK phosphorylation (pERK1/2), but quickly reactivate pERK1/2 in 8505C cells. Vemurafenib could only quickly activate AKT phosphorylation (pAKT) and slightly activate phosphorylation JNK1/2(pJNK1/2). However, vemurafenib in combination with PEAK1 deletion inhibited reactivation of pERK1/2 and pAKT activation, and promoted pJNK1/2. Vemurafenib transiently and slightly upregulated pro-apoptotic PUMA and Bim expression, which was quickly disappeared with long time vemurafenib treatment. Combined PEAK1 depletion and Vemurafenib treatment upregulated JNK1/2-dependant Bim and AKT-dependant PUMA expression. PUMA and Bim upregulation is critical for vemurafenib induced apoptosis in presence of PEAK1 deletion. Vemurafenib resistance in 8505C cells is associated with PEAK1 activation, pERK1/2 re-activation, pJNK1/2 inactivation and AKT activation, resulting in the inhibition of AKT-dependent PUMA and pERK1/2-pJNK1/2-dependent Bim expression. PEAK1 depletion could inhibited both ERK1/2 and AKT signal and released PUMA and Bim from vemurafenib-treated cells, resulting in the enhancing cell apoptosis. Therefore, targeting PEAK1 may be an effective strategy to sensitize BRAF-mutant ATC to vemurafenib.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology. Clinical manifestations include dyspnea and nonproductive cough. Lung transplantation is the only cure, while Pirfenidone and Nintedanib are FDA-approved drugs for slowing disease progression. However, Saracatinib shows greater efficacy. This literature review assesses the safety and efficacy of IPF treatments, focusing on Pirfenidone and Nintedanib, which preserve lung function and reduce fibrosis and inflammation. We also evaluate emerging treatments such as saracatinib, pamrevlumab, pentraxin-2, BI 1015550, ziritaxestat, PBI-4050, bexotegrast, BMS-986020, TD 139, dasatinib, quercetin, and etanercept. Additional research is needed to explore the therapeutic potential and address gaps in IPF management, including exacerbation and associated pulmonary hypertension (PH). Immunosuppressive agents are used to manage IPF exacerbations, while PH is a recognized comorbidity. Clinical trials, PULSAR and SPECTRA, investigate Sotatercept as a potential PH treatment for IPF patients, showing promising results.

Malaxis ybytui is proposed as a new species from the wetlands of the Campos de Altitude of the Atlantic Rainforest of South Brazil. It is described, illustrated, and compared with other similar species. The new species is recognised by its flat to slightly conduplicate leaves, densely congested inflorescence with small flowers bearing free lateral sepals and four cavities in the lip. It is similar to Malaxis cipoensis and Malaxis sertulifera, being distinguished by its vegetative and floral morphology. The species is found in the mountain’s hillside about 1500m elevation in the Serra do Araçatuba\Papanduva mountain chain. Due to the high degree of endemism in this environment, the few collection records and the anthropic pressure in the region, we infer that the species is Critically Endangered (CR).

Objective To identify the biomarkers of papillary thyroid carcinoma and explore the possible pathogenic mechanism. Methods The cancer tissues of 5 patients with papillary thyroid carcinoma and adjacent normal thyroid tissues were analyzed for protein expression by TMT proteomics technology. Differentially expressed proteins were screened and identified, and functional annotation of differentially expressed proteins was carried out by bioinformatics and pathway enrichment analysis. Results A total of 639 differential proteins were identified, including 278 up-regulated proteins and 361 down-regulated proteins. Among them, six up-regulated proteins are expected to become specific markers of PTC. Conclusion Based on the above research results, differential proteins may become new molecular markers of papillary thyroid carcinoma, and these differential proteins and their enrichment pathways can provide new insights into its pathogenic mechanism ideas and directions.

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is characterized by chronic gastrointestinal inflammation. A high unmet need exists for non-invasive biomarkers in IBD to detect mucosal inflammation to monitor changes in disease severity and guide treatment decisions. Fecal proteomics has the potential to allow frequent, non-invasive monitoring of biomarkers in stool of IBD patients, however the fecal proteome remains under explored. Here a data-independent acquisition LC-MS/MS approach was used to profile the human fecal proteome in two independent cohorts of IBD patients and healthy controls (HC) to identify non-invasive biomarkers reflective of disease activity. 688 human proteins were quantified, with 523 measured in both cohorts. In UC stool 96 proteins were differentially abundant and in CD stool 126 proteins were differentially abundant compared to HC stool (absolute log2 fold change >1, p-value <0.05). Many of these fecal proteins are associated with infiltrating immune cells and ulceration/rectal bleeding, which are hallmarks of IBD pathobiology. Mapping of the identified fecal proteins to a whole blood single-cell RNA sequencing data set revealed the involvement of various immune cell subsets to the IBD fecal proteome. Findings from this study not only confirmed the presence of established fecal biomarkers for IBD, such as calprotectin and lactoferrin, but also revealed new fecal proteins from multiple pathways known to be dysregulated in IBD. These novel proteins could serve as potential non-invasive biomarkers to monitor specific aspects of IBD disease activity which could expedite clinical development of novel therapeutic targets.

Aim: Assessment of the effects of moderate exercise on lipopolysaccharide (LPS)-triggered lung injury. Method: Thirty-two male Wistar rats were divided into four groups of eight as follows: (1) control; (2) LPS; (3) exercise (EX); and (4) exercise+ LPS (EX+LPS). Exercise groups were submitted to exercise (15 m/min for 30 min, 6 days/week, for a period of 8 weeks). LPS (1 mg/kg) was intraperitoneally injected on a daily basis for 5 successive days during the last week of the experiment. Ultimately, the levels of stress oxidative markers in the bronchoalveolar lavage fluid (BALF) and in lung tissues, total white blood cells (WBC) counts in the BALF, inflammatory markers in lung tissue, tracheal responsiveness to methacholine, and lung histopathological changes were assessed. Results: LPS injection increased the number of total WBC, neutrophils, eosinophils, monocytes, and lymphocytes as well as malondialdehyde (MDA) levels in the BALF, tumor necrosis factor-α (TNF-α), interleukin (IL)- 1β, and MDA in lung tissues, and tracheal responsiveness to methacholine, and caused lung pathological damages (P<0.05-P<0.001). Moderate exercise preconditioning decreased total WBC, neutrophils, eosinophils, monocytes, and lymphocytes counts in the BALF, diminished levels of TNF-α, IL-1β, and MDA in the lung, but increased thiol levels in lung tissues (P<0.05-P<0.01). Furthermore, moderate exercise alleviated tracheal hyper-responsiveness (P<0.01). Conclusion: Moderate training improved LPS-induced lung injury by attenuating lung inflammatory cytokine levels, oxidative damage, and pathological changes and tracheal hyper-responsiveness.

Background: Timely detection and appropriate treatment of Acute antibody mediated rejection (AMR) would affect long-term survival of allograft. This study was designed to discover non-invasive biomarkers in prediction of response to therapy in AMR patients. Material and methods: in this case- control study, urine samples of 21 biopsy proven AMR patients were were subjected to proteomics with label free quantification. Patients were allocated into two groups of responders and non- responders to treatment. Urine proteins were identified and their expressions were compared in two groups in order to discover potential candidate biomarkers. Results: From 1020 identified proteins, 257 proteins were differentially expressed between groups among them 153 and 104 proteins increased and decreased in non- responder patients respectively. Complement pathway was more active in non-responders than responders and, extracellular matrix proteins were mainly reduced in non-responders. IGFBP-6 were determined as the most sensitive and specific biomarker in prediction of non-responder patients. Conclusion: According to the role of IGFBP-6 in apoptosis induction and tubular damage, up-regulation of this protein could be a good predictor of response to treatment in AMR patients and treatment approach could be determined based on IGFBP_6 changes. Further studies are needed to confirm these findings.

To determine distinct phenotype groups in patients with idiopathic inflammatory myopathy (IIM), and to identify the differences of clinical characteristics, laboratory findings, and the long-term outcomes in patients with antisynthetase syndrome (ASS) of different anti-aminoacyl-tRNA synthetase (ARS) antibodies. Methods: We enrolled retrospectively 280 patients with IIM, and the clinical characteristics and laboratory findings were collected. Additionally, multivariate COX regression analysis was performed to identify indicators of poor prognosis in patients with ASS. Results: 119 ASS and 161 non-ASS patients were identified in 280 patients with IIM, the occurrence rates of ILD, RP-ILD, pulmonary symptoms, arthritis, triad and mechanic’s hands with ASS group were more prevalent than non-ASS group ( p＜0.05). Among 119 patients with ASS, the highest incidence of RP-ILD occurred in the PL12 group (36.4%). There was clinical significance of statistical differences in arthritis, myositis, mechanic’s hands, triad, shawl sign, v sign, and Raynaud’s phenomenon among the 4 subgroups ( p＜0.05). At the same time, the individuals in the positive anti-Jo1 antibody group were more likely to exhibit arthritis, myositis, mechanic’s hands, triad and, v sign than the negative anti-Jo1 antibody group in patients with ASS, furthermore, statistically more prevalent ( p＜0.05). According to the multivariate COX regression analysis, mechanic’s hands, ANA, and ILD were independent risk factors for poor prognosis in patients with ASS ( p<0.001, p=0.026, and p<0.001, respectively). V sign was an independent protective factor for good prognosis in patients with ASS ( p=0.026). Conclusions: When clinical characteristics including pulmonary symptoms, arthritis, mechanic’s hands, ANA, along with ILD appear, clinicians should be on the alert for the occurrence of ASS in patients with IIM

THE ASSESMENT OF ANGIOSPERM FLORISTIC DIVERSITY IN PACHAMALAI HILLS OF EASTERN GHATS TOWARDS THE EX SITU CONSERVATION OF BIODIVERSITY

Viola pendulipedunculata (Violaceae), a new species from Baiwan Nature Reserve of Guangdong Province in China, is described and illustrated. The new species is most similar to V. nanlingensis morphologically, but it can be easily distinguished by its narrowly oblong anterior petals (vs. spatulate anterior petals), curved and drooping peduncles (vs. erect peduncles), and seed with obvious elaiosome (vs. inconspicuous elaiosomes) and the whole plant. Our phylogenetic analysis, based on ITS sequences, confirms that the new species belongs to V. sect. Diffusae, and mostly related to V. yunnanensis in the phylogeny.

OBJECTIVE To investigate how tubeimoside III inhibits lipopolysaccharide(LPS)-induced inflammatory responses by reprogramming glucose metabolism. METHOD A mouse model of LPS-induced acute inflammation was constructed, and the protective effect of tubeimoside III against LPS-induced injury was investigated using histochemistry and real-time quantitative PCR. Western blotting, Seahorse extracellular flux analyser assays, and pyruvate content assays were used in LPS-induced RAW264.7 cells to explore how tubeimoside III exerts its anti-inflammatory effects. The potential mechanism was also validated using inhibitors. RESULTS Tubeimoside III significantly attenuated the expression of inflammatory cytokines IL-6, IL-1β, and iNOS in lung and liver tissue homogenates and RAW264.7 cells. This agent inhibited inflammatory cell infiltration in alveoli and prevented necrosis in liver lesions in LPS-treated mice. Extracellular flux analyser assays revealed that tubeimoside III regulated glucose metabolism in RAW264.7 cells. Real-time quantitative PCR and western blot revealed that tubeimoside III had similar effects on the downstream effector molecule of itaconic acid. An inhibitor weakened the inhibitory effect of tubeimoside III on the expression of inflammatory factors. CONCLUSIONS Tubeimoside III protects against LPS-induced lung and liver injury by attenuating inflammatory factor secretion and inflammatory cell infiltration, and its mechanism of action involves reprogramming macrophage glucose metabolism and increasing itaconic acid levels.

Our goal was to explore the potential continuity between motor activity observed in early social situations and communication development. Thirteen infants between 4 and 6 months of age were observed in daycare centers, either on their own or in dyads, and in two postural conditions: lying on a playmat or seated in bouncers. Infants were found to modify their posture, movements and gaze behavior in dyadic situations compared to situations alone. Moreover, the bouncers facilitated visual interactions while the playmat favored the production of hand movements. This work highlights the need to analyze multimodal characteristics of interactions and to add posture variations as a key variable to better understand how infants develop communicative intention toward their peers.

The purpose of this study is to conduct validity and reliability tests of the Anatolian Preschool Mathematics (ANOMAT) Skills Scale, developed to measure the mathematical skills of children aged 36-85 months. In this context, the scale was individually administered to a total of 471 children selected through stratified sampling from families with low, middle, and high socio-economic status with normal development in the province of Eskisehir/Türkiye. The structural validity of the ANOMAT Skills Scale was tested with confirmatory factor analysis, and the McDonald’s Omega and Cronbach’s Alpha (Alpha ordinal) reliability coefficients of the factors were calculated. The results showed that the ANOMAT Skills Scale consisting of 156 items and four factors (numbers, operations, measurement, and geometry) is a valid and reliable tool for assessing the early mathematical skills of children aged 36-85 months.

The home environment is one of the most proximal and impactful settings for young children. Little research has examined the nature of variability in the home environment for children from low-income homes, even as more recent work suggests heterogeneity within economically disadvantaged households. Using a subsample from a larger, longitudinal study, we examined the extent to which differential profiles of the home environment of infants from low-income backgrounds could be identified. A latent profile analysis (LPA) suggested three profiles of the home environment: low home environment, average home environment, and high involvement. These three groups did not differ on family characteristics such as parental education, income, or marital status but did differ with respect to maternal stress and material support. Specifically, maternal stress and material support were lower in the group with high involvement.

Rheumatoid arthritis (RA) is a systemic autoimmune disease driven by highly active autoantibody producing B cells. These B cells can be supported within ectopic germinal centers found in afflicted joints. Fibroblast like synoviocytes (FLS) present in inflamed joints support B cell survival, activation and differentiation. CD27 + memory B cells and naïve B cells show very distinct reactions to activation, particularly by CD40 ligand (CD40L). We show that FLS dependent activation of human B cells is dependent on interleukin 6 (IL-6) and CD40L. FLS have been shown to activate naïve as well as memory B cells. If the activatory potential of FLS is different for naïve and memory B cells had not yet been investigated. Our results suggest that FLS-induced activation of B cells is dependent on IL-6 and CD40L. While FLS are capable of inducing differentiation, isotype switching and antibody production in memory B cells, FLS capability to activate naive B cells is significantly lower.

Introduction Alcohol withdrawal syndrome (AWS) is a serious illness that can occur when a person who is an alcoholic abruptly stops drinking. The symptoms can range from mild to severe and include physical symptoms such as tremors, anxiety, nausea, vomiting, headache, sweating, rapid heart rate, high blood pressure, and insomnia; psychological symptoms such as depression, irritability, restlessness, and concentration difficulties; and behavioural symptoms such as social withdrawal and aggression. In certain cases, symptoms may be mild and resolve on their own within a few days. The majority of previous research on alcohol withdrawal has focused on physical symptoms, such as tremors, perspiration, and anxiety. Case summary This is a one-of-a-kind case of a long-term alcoholic who voluntarily quit drinking. As a consequence of alcohol withdrawal, he developed AWS symptoms. Tragically, despite the struggles he faced, he did not seek appropriate medical care, ultimately leading to his decision to take his own life. Conclusion Suicide in AWS is a preventable complication if we provide adequate treatment for AWS and underlying alcoholism. This case report emphasizes the importance of recognizing and managing AWS under supervision either institutional or in home and the possible association with suicide risk in alcoholics if not managed expeditiously.

Collecting expeditions carried out in the Zamboanga Peninsula of western Mindanao led to the rediscovery of Thottea philippinensis, previously known only by a single collection made 93 years ago in the Philippines. Thus, in this paper, we provide descriptions, comments on the affinities among closely related species, an updated geographical distribution, habitat information, conservation assessment, and the first-ever published photos of living T. philippinensis in the wild. Additionally, we include notes on confirming the occurrence of T. tomentosa in the Philippine archipelago.

Lecythis zabucajo lectotype was proposed with a mistake regarding the number of the plate. To fulfill the code, this detail is here fixed.

Commelina badamica var. palakondensis ……….var. nov. (Commelinaceae), a remarkable new variety from Palkonda hills of Eastern Ghats of Peninsular India is described and illustrated. It is apparently similar to C. badamica in habitat ecology and general morphology, but strictly differs in features like presence of 2-3 nerved ligule, lower cincinnus with single bisexual flower, ovary glabrous, anthers-elliptic and seeds ovoid-oblong or trapezoidal. In addition to description, habitat ecology, details on population distribution and the conservation status are also provided for the new variety.

The emergence of 16S rRNA and metagenomic sequencing has gradually revealed the close relationship between dysbiosis and colorectal cancer (CRC). Recent studies have confirmed that intestinal dysbiosis plays various roles in the occurrence, development, and therapeutic response of CRC. Perturbation of host immunity is one of the key mechanisms. Intestinal flora, or specific bacterium and its metabolites can modulate the progression of CRC through Toll-like receptors signaling, or via the recruitment, polarization and activation of innate and adaptive immune cells to reshape the pro-/anti-tumor microenvironment. On this basis, administration of gut bacteria to enhance immune homeostasis represents new cues for the treatment of CRC. In this review, we will cover the recent studies on the role of gut bacteria in the progression and treatment of CRC through immune response orchestration, which potentially offers insights for subsequent transformative research.

Gynodioecy has been identified to occur in the herbaceous polycarpic Origanum vulgare ssp. gracile growing in Tajikistan and is here described in detail for the first time. The investigated populations of O. vulgare ssp. gracile form two types of flowers, perfect and pistillate, on different individuals. In pistillate flowers, stamens are represented by staminodes. The size of many parts of the corolla and androecium of perfect flowers is significantly larger than in pistillate flowers. Four criteria have been identified that make it possible to reliably distinguish flowers of different sexual forms: the size of the corolla and its parts, the difference between calyx tube length versus corolla tube length, the position of the anthers, and the rate of development of stamens. Perfect flowers are characterized by strictly pronounced protandry. According to the pollen/ovule ratio (from 825 to 953), O. vulgare ssp. gracile is facultatively xenogamous. Hermaphrodites predominated (from 58.9% to 76.2%) in five of the investigated populations. The frequency of females in O. vulgare ssp. gracile was shown to be most dependent on annual precipitation (Bio12). Finally, we discuss the presence and distribution of gynodioecy within the genus Origanum and its adaptive significance for the existence of populations of O. vulgare ssp. gracile.

Melastomataceae is one of the largest families of flowering plants, comprising approximately 5,858 species distributed across 173 genera worldwide. Brazil excels as the country with the highest diversity of Melastomataceae in the neotropical Americas, boasting 1,453 species with a significant number of endemisms. The Caatinga, a phytogeographic domain in Brazil, holds a prominent position as the core area of Seasonally Dry Tropical Forests and Shrubs and Woodlands (SDTFSW) in South America and exhibits remarkable environmental heterogeneity, featuring various phytophysiognomies associated with both crystalline and sedimentary terrains. Within this domain, rock outcrops support endemic and rare species, further enhancing the ecological value of this region. Although Melastomataceae has limited representation in the Caatinga, the colonization of xeric environments by select species of this family has attracted attention. Notably, the discovery of Pleroma caatingae stands out, an endangered species previously thought to be endemic to the state of Bahia, and recently collected outside the state. This paper presents the first record of the species outside Bahia. After acquiring further morphological data, an adapted description of this species is offered, incorporating information from these peripheral occurrence points. To enhance understanding of the potential distribution and conservation status of the species, a conducted predictive species distribution model (SDM) that provides an updated account of its geographical range is presented. Furthermore, comprehensive insights regarding phenology and conservation status are provided. Additionally, conclusions are drawn pertaining to the remaining knowledge gaps surrounding the distribution of neotropical species and their interrelationships with both their counterparts and their surroundings and provides innovative insights and outlooks regarding the preservation of arid habitats, which are typically overlooked but hold intriguing discoveries for biodiversity.

Organic crystals that can respond to external stimuli and exhibit fluorescence changes have drawn increasing attention recently as their potential applications in intelligent displays, optical data storage, anticounterfeiting, bioimaging, and sensors. Herein, we have synthesized two new organic compounds based on frameworks of anthracene and pyridine groups: 4-(anthracen-9-yl) pyridine (AN9P) and 4-(anthracen-2-yl) pyridine (AN2P). Both compounds, in solutions and solid states including polycrystals and single crystals, display reversible fluorescence transformations under alternative acid and base treatments. AN9P and AN2P solutions could be regulated to emit white light luminescence. The photoluminescence of AN9P and AN2P polycrystals showed fast fluorescence changes with wide ranges (>300 nm) upon alternative acid and base stimuli and still exhibited remarkable fluorescence emission with almost no attenuation after 15 cycles of the reversible process. Both experimental and computational calculation results suggested that the heteroatom nitrogen in the AN9P and AN2P molecules significantly influenced the intra- and intermolecular electronic interactions during the reversible protonation and deprotonation processes, resulting in changes in their frontier molecular orbitals and fluorescence emission characteristics. Our results provide a new facile approach to designing molecular structures to realize highly dynamic photoluminescence changes in both liquid solution and solid crystal.