Diseases Research Articles

Ideal animal models according to multifaceted mechanisms and peculiarities in neurological disorders: present and challenges.

Neurological disorders, encompassing conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), pose a significant global health challenge, affecting millions worldwide. With an aging population and increased life expectancy, the prevalence of these disorders is escalating rapidly, leading to substantial economic burdens exceeding trillions of dollars annually. Animal models play a crucial role in understanding the underlying mechanisms of these disorders and developing effective treatments. Various species, including rodents, non-human primates, and fruit flies, are utilized to replicate specific aspects of human neurological conditions. However, selecting the ideal animal model requires careful consideration of its proximity to human disease conditions and its ability to mimic disease pathobiology and pharmacological responses. An Animal Model Quality Assessment (AMQA) tool has been developed to facilitate this selection process, focusing on assessing models based on their similarity to human conditions and disease pathobiology. Therefore, integrating intrinsic and extrinsic factors linked to the disease into the study's objectives aids in constructing a biological information matrix for comparing disease progression between the animal model and human disease. Ultimately, selecting an ideal animal disease model depends on its predictive, face, and construct validity, ensuring relevance and reliability in translational research efforts.

Prevalence of non-tuberculous mycobacteria among people with acid-fast positive presumptive tuberculosis in Mali.

Non-tuberculous mycobacteria (NTM) are environmental agents that can cause opportunistic pulmonary disease in humans and animals, often misdiagnosed as tuberculosis (TB). In this study, we describe the cases of NTM identified during the first national anti-TB drug resistance survey conducted in Mali and explore associated risk factors. Sputum was collected from people presenting for pulmonary TB diagnosis from April to December 2019, regardless of age. Microscopy-positive patients were enrolled and tested using the Xpert MTB/RIF assay. A patient who tested negative for the Mycobacterium tuberculosis complex (MTBC) was tested for the presence of mycobacteria by amplification of the IS6110 and 16SrRNA (16S) genes through double quantitative real-time PCR, followed by nested PCR and Sanger sequencing of the IS6110-negative samples for NTM species identification. 1,418 sputum smear-positive patients were enrolled, including 1,199 new cases, 211 previously treated cases, and 8 whose previous treatment history was unknown. Based on the results of Xpert MTB/RIF assay and in-house PCR methods, 1,331 (93.9%) patients were positive for MTBC, 48 (3.4%) for NTM, and no species identification was possible for 39 (2.7%). Advanced age of 65 and over with an OR 8.8 (95% CI 2.3-33.2 and p = 0.001) and previous TB treatment with an OR 3.4 (95% CI 1.2-9.6 and p = 0.016) were the risk factors statistically associated with NTM detection. M. avium complex (MAC) was the predominant NTM species, detected in 20 cases. Detection of NTM in people presumed to have TB is an ongoing challenge, confounding correct TB diagnosis. Concomitant use of microscopy and GeneXpert testing among at-risk individuals could improve patient management.

A Randomized, Blinded, Vehicle-Controlled Dose-Ranging Study to Evaluate and Characterize Remdesivir Efficacy Against Ebola Virus in Rhesus Macaques

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure. Thirty rhesus macaques underwent surgical implantation of telemetry devices for the fine-scale monitoring of body temperature and activity, as well as central venous catheters, to enable treatment administration and blood collection. Treatment, consisting of a loading dose of RDV followed by once-daily maintenance doses for 11 days, was initiated 4 days after virus exposure when all animals were exhibiting disease signs consistent with incipient EBOV disease as well as quantifiable levels of EBOV RNA in plasma. In the RDV treatment groups receiving loading/maintenance doses of 5/2.5 mg/kg, 10/5 mg/kg, and 20/10 mg/kg, a total of 6 of 8 (75%), 7 of 8 (87.5%), and 5 of 7 (71.4%) animals survived, respectively. In the vehicle control group, one of seven animals (14.3%) survived. The improved survival rate compared to the control group was statistically significant only for the 10/5 mg/kg RDV treatment group. This treatment regimen also resulted in a significantly lower systemic viral load compared to the vehicle control after a single RDV treatment. All three RDV regimens produced a significantly lower systemic viral load after two treatments. For most animals, RDV treatment, regardless of dose, resulted in the amelioration of many of the clinical–pathological changes associated with EBOV disease in this model.

FTO in health and disease

Fat mass and obesity-associated (FTO) protein, a key enzyme integral to the dynamic regulation of epitranscriptomic modifications in RNAs, significantly influences crucial RNA lifecycle processes, including splicing, export, decay, and translation. The role of FTO in altering the epitranscriptome manifests across a spectrum of physiological and pathological conditions. This review aims to consolidate current understanding regarding the implications of FTO in health and disease, with a special emphasis on its involvement in obesity and non-communicable diseases associated with obesity, such as diabetes, cardiovascular disease, and cancer. It also summarizes the established molecules with FTO-inhibiting activity. Given the extensive impact of FTO on both physiology and pathophysiology, this overview provides illustrative insights into its roles, rather than an exhaustive account. A proper understanding of FTO function in human diseases could lead to new treatment approaches, potentially unlocking novel avenues for addressing both metabolic disorders and malignancies. The evolving insights into FTO’s regulatory mechanisms hold great promise for future advancements in disease treatment and prevention.

Amoebae: beyond pathogens- exploring their benefits and future potential

Amoebae, fascinatingly diverse protists, showcase a dual nature that positions them as both friends and foes in our world. These organisms, defined by their distinctive pseudopodia, span a spectrum from harmful to helpful. On the darker side, species like Entamoeba histolytica pose serious health risks, causing intestinal and liver diseases, while the infamous “brain-eating” Naegleria fowleri leads to fatal primary amoebic meningoencephalitis (PAM), with a daunting 97% mortality rate. Other free-living amoebae, including Acanthamoeba castellanii and Balamuthia mandrillaris, also threaten the human central nervous system. Yet, beyond these dangers, amoebae play critical ecological roles. They function as nature’s recyclers, decomposing organic material and nourishing aquatic ecosystems, while also serving as food for various organisms. Moreover, certain amoebae help control plant pathogens and offer insight into human disease, proving valuable as model organisms in biomedical research. This review sheds light on the complex, multifaceted world of amoebae, highlighting their dual role as pathogens and as key contributors to vital ecological processes, as well as their significant impact on research and their promising potential for enhancing human well-being.

Gingival crevicular fluid Bax, Bcl-xl, interleukin-22, and transforming growth factor beta 1 levels in stage III periodontitis.

Intrinsic apoptosis plays a critical role in immune defense and inflammation. Its dysregulation is involved in various chronic diseases. The B-cell lymphoma 2 (Bcl-2) family primarily mediates this mitochondrial pathway. This study aimed to investigate the proapoptotic Bcl-2-associated X protein (Bax) and antiapoptotic B-cell lymphoma-extra large (Bcl-xl) levels and their association with interleukin-22 (IL-22) and transforming growth factor beta 1 (TGF-β1) in the gingival crevicular fluid (GCF) of patients with periodontitis. A total of 75 systemically healthy nonsmokers were enrolled, of whom 23 had stage III periodontitis, 26 had gingivitis, and 26 were periodontally healthy. Whole-mouth clinical periodontal measurements were recorded. Bax, Bcl-xl, IL-22, and TGF-β1 levels in the GCF were determined by enzyme-linked immunosorbent assay (ELISA). Data were analyzed using nonparametric statistical tests. The periodontitis group had significantly lower GCF Bax levels than the gingivitis group (p<0.05). The periodontitis and gingivitis groups had higher GCF Bcl-xl levels than the periodontally healthy group (p<0.05). GCF IL-22 levels were similar in all groups (p>0.05). The periodontitis group had lower GCF TGF-β1 levels than the gingivitis and periodontally healthy groups (p<0.05). The diseased groups had a lower GCF Bax/Bcl-xl ratio than the healthy controls (p<0.05). IL-22 was positively correlated with Bax (p<0.05). This is the first study investigating GCF Bax and Bcl-xl levels in periodontal health and disease. Increased GCF Bcl-xl levels and a decreased Bax/Bcl-xl ratio in stage III periodontitis implicate that those apoptotic proteins may be involved in the pathogenesis of periodontal disease. Further studies are needed to enlighten the possible role of Bax and Bcl-xl and their association with IL-22 and TGF-β1 in periodontal diseases. A type of cell death called intrinsic apoptosis plays an important role in the body's defense system, and its dysregulation is linked to different human diseases. The B-cell lymphoma 2-associated X protein (Bax) and B-cell lymphoma-extra large (Bcl-xl) are apoptosis-related proteins, which promote and inhibit cell death, respectively. This study aimed to investigate Bax and Bcl-xl levels and their association with the signaling proteins interleukin-22 (IL-22) and transforming growth factor beta 1 (TGF-β1) in the gingival crevicular fluid (GCF), which accumulates around the necks of the teeth of patients suffering from gum diseases such as gingivitis and periodontitis. Clinical parameters were recorded and GCF was collected. Bax, Bcl-xl, IL-22, and TGF-β1 levels were measured by biochemical assay in periodontally healthy individuals who had healthy gums (n=26) and patients with periodontitis (n=23) and gingivitis (n=26). Periodontitis patients had lower Bax levels than gingivitis patients. Periodontitis and gingivitis patients had higher Bcl-xl levels and a lower Bax/Bcl-xl ratio than periodontally healthy individuals. IL-22 was positively correlated with Bax. The present findings suggest that the apoptotic regulatory molecules may be involved in the development of gum diseases, highlighting the need for further research in this area.

Bacterial attachment and junctional transport function in induced apical-out polarized and differentiated canine intestinal organoids

Dogs are increasingly recognized as valuable large animal models for understanding human intestinal diseases, as they naturally develop conditions similar to those in humans, such as Enterohemorrhagic E. coli, Clostridium difficile infection, inflammatory bowel disease, and ulcerative colitis. Given the similarity in gut flora between dogs and humans, canine in vitro intestinal models are ideal for translational research. However, conventional extracellular matrix-embedded organoids present challenges in accessing the lumen, which is critical for gut function. This study aimed to investigate the feasibility of inducing polarity reversal and differentiation in canine apical-out colonic organoids (colonoids), evaluate their barrier integrity, and visualize host-pathogen interactions. Our results demonstrated successful polarity reversal and differentiation induction while maintaining barrier integrity. Polarity reversal allowed for enhanced observation of host-pathogen interactions, facilitating visual assessments and membrane integrity evaluations using both pathogenic and nonpathogenic E. coli. This process led to the downregulation of stem cell marker LGR5 and upregulation of intestinal epithelial cell marker ALPI, indicating differentiation. Further differentiation was observed with the use of a differentiation culture medium, resulting in significant upregulation of ALPI and goblet cell marker MUC2. The findings suggest that apical-out canine colonoids can serve as physiologic and valuable models for studying the pathogenic mechanisms and clinical significance of intestinal diseases in dogs. This model has the potential to advance both canine and human gastrointestinal research, enhancing our understanding of gastrointestinal physiology and pathology and aiding in the development of novel therapeutics.

PCAT19: the role in cancer pathogenesis and beyond

PCAT19, a long non-coding RNA, has attracted considerable attention due to its diverse roles in various malignancies. This work compiles current research on PCAT19’s involvement in cancer pathogenesis and progression. Abnormal expression of PCAT19 has been observed in various cancers, and its correlation with clinical features and prognosis positions it as a promising prognostic biomarker. Additionally, its ability to effectively differentiate between tumor and normal tissues suggests significant diagnostic value. PCAT19 exhibits a dual nature, functioning either as an oncogene or a tumor suppressor, depending on the cancer type. It is implicated in a range of tumor-related activities, including cell proliferation, apoptosis, invasion, migration, metabolism, as well as tumor growth and metastasis. PCAT19 acts as a competing endogenous RNA (ceRNA) or interacts with proteins to regulate critical cancer-related pathways, such as MELK signaling, p53 signaling, and cell cycle pathways. Furthermore, emerging evidence suggests that PCAT19 plays a role in the modulation of neuropathic pain, adding complexity to its functional repertoire. By exploring the molecular mechanisms and pathways associated with PCAT19, we aim to provide a comprehensive understanding of its multifaceted roles in human health and disease, highlighting its potential as a therapeutic target for cancer and pain management.

Diet shapes and maintains the personalized native gut microbiomes in mice.

The gut microbiome plays a critical role in human health and disease. Different dietary backgrounds play an important role in the uniqueness and diversity of the gut microbiota in different individuals, which promotes heterogeneity in disease phenotypes and treatment responses. Here, we explored how diet affects the composition and function of the native gut microbiome of model mice, based on the shotgun metagenomic and metabolomic, by analyzing the gut microbiome of C57B/6J mice in different dietary backgrounds. The gut microbiomes of mice receiving different diets consistently exhibit distinct compositions across bacterial species, strains, fungi and phages. This implies that native microbial communities cannot 'homogenize' rapidly becaise of priority effects and unchanging diets. Notably, hotspot bacteria such as Limosilactobacillus reuteri, Parabacteroides distasonis and Akkermansia muciniphila were significantly different among the groups. These species harbor diverse adaptive mutations, reflecting genomic evolutionary diversity. The functional profiles of the gut microbiota also exhibit selective differences, involving the capacity for carbohydrate, branched-chain amino acid and fatty acid synthesis, as well as virulence factors, carbohydrate-active enzymes and antibiotic resistance. Furthermore, the differences in the gut microbiota also propagate to the host's serum, where structural and specific metabolite differences were observed. Metabolites that directly impact host health, such as d-glucosamine 6-phosphate and testolic acid, also show significant differences between the different dietary groups. Our findings underscore the profound influence of different dietary the composition and functionality of the gut microbiome, offering valuable insights into optimizing health outcomes through personalized nutritional interventions. © 2024 Society of Chemical Industry.

In-Depth Phenotyping of PIGW-Related Disease and Its Role in 17q12 Genomic Disorder

Glycosylphosphatidylinositol (GPI) biosynthesis defect 11 (GPIBD11), part of the heterogeneous group of congenital disorders of glycosylation, is caused by biallelic pathogenic variants in PIGW. This rare disorder has previously been described in only 12 patients. We report four novel patients: two sib fetuses with congenital anomalies affecting several organs, including the heart; a living girl with tetralogy of Fallot, global developmental delay, behavioral abnormalities, and atypic electroencephalography (EEG) without epilepsy; a girl with early-onset, treatment-resistant seizures, developmental regression, and recurrent infections, that ultimately passed away prematurely due to pneumonia. We also illustrate evolving facial appearance and biochemical abnormalities. We identify two novel genotypes and the first frameshift variant, supporting a loss-of-function pathogenic mechanism. By merging our cohort with patients documented in the literature, we deeply analyzed the clinical and genetic features of 16 patients with PIGW-related disorder, revealing a severe multisystemic condition deserving complex management and with uncertain long-term prognosis. We consider the role of PIGW within the critical 17q12 region, which is already associated with genomic disorders caused by deletion or duplication and characterized by variable expressivity. Finally, we discuss PIGW dosage effects and a second hit hypothesis in human development and disease.

Unlocking the pharmacological potential of Brennnesselwurzel (Urtica dioica L.): an in-depth study on multifaceted biological activities

Brennnesselwurzel (Urtica dioica L.) is recognized for its diverse pharmacological properties. With a range of chemical constituents, such as vitamins, minerals, phenolic compounds, fibers, and amino acids, Brennnesselwurzel (BWE) has a long history of traditional medicinal use in Europe and Asia. The correlation between a plant's metabolite composition and its activity can vary depending on considerations such as geographic location, environmental conditions, and genetic variations. In the present study, we explore the phytochemical profile and biological activity of the 70% acetone extract of the BWE plant. The chemical profile of the BWE extract was explored using several techniques, including amino acid analyzer, HPLC, GC–MS, and other colorimetric analysis. The antioxidant activity of the BWE extract was assessed by evaluating the total antioxidant, free radical scavenging activity (DPPH, ABTS, H2O2), and metal chelating scavenging activity (FRAP, CUPRAC, metal chelating). Furthermore, we assessed the antimicrobial and antiproliferation activities of the BWE extract against 29 microbial strains and 15 cell lines, respectively. Our phytochemical analyzes revealed that the BWE extract has a unique profile of metabolites including amino acids, flavonoids, phenolics, volatile oils, lipids, and vitamins. The BWE extract showed a total antioxidant capacity of 30.94 ± 1.58 mg GAE/g, together with potential free radical scavenging activity towards ABTS (IC50 = 153.51 ± 3.97 µg/ml), DPPH (IC50 = 195.75 ± 5.91 µg/ml), and H2O2 (IC50 = 230.67 ± 5.98 µg/ml). Although the BWE extract showed no significant antifungal activity, our findings revealed that the BWE extract possesses substantial antibacterial activity against Staphylococcus epidermidi, Streptococcus mutants, Enterococcus faecalis, Micrococcus sp., Klebsiella pneumonia and Porphyromonas gingivalis. Furthermore, the BWE extract demonstrated potential antiproliferative activity toward a panel of cancer cell lines with a high selectivity index. Among the cells examined, the BWE extract exhibited significant cytotoxic activity toward HCT-116, A-549, MDA-MB-231 cells with IC50 of 15.11, 15.32, 15.79 µg/mL, respectively, while it possessed no significant cytotoxic activity towards WI-38 cells (IC50 119.62 µg/mL). Taken together, our findings reveal that BWE extract possesses a wide spectrum of biological activities, including antioxidant, antibacterial, and antitumor activities, and could be considered for further research to explore its potential as a natural plant-based supplement for human diseases.

Three novel neoplasms in Nancy Ma's owl monkeys (Aotus nancymaae).

Neoplasms are only sporadically reported in New World primates and rarely in owl monkeys (Aotus spp.), specifically. Previous reports of neoplasms in owl monkeys are primarily restricted to lymphoma induced by Herpesvirus saimiri infection, although other tumors in the central nervous, genitourinary, gastrointestinal, and endocrine systems have been sporadically reported. Herein, we describe 3 previously unreported neoplasms in owl monkeys (Aotus nancymaae) including a pericardial mesothelioma in a 6-year-old male, a nephroblastoma in a 2-year-old male, and a cervical neoplasm with characteristics of an epithelioid trophoblastic tumor in a 4-year-old female, all occurring in the same closed breeding colony at a research facility in central Texas. Reporting of spontaneously occurring neoplasms in research colony populations is important for identifying potential animal models of human diseases and for improving colony management and species health.

INVOLVEMENT OF HLA-DRB1*11 AND HLA-DRB1*12 ALLELES IN THE OCCURRENCE OF DENGUE FEVER IN BURKINA FASO

Introduction: Dengue has become the world's most common arbovirosis. In some individuals, genetic factors can increase the risk of developing severe dengue fever. Human leukocyte antigen (HLA) genes are one of the most extensively studied gene groups in human disease. The present study investigated HLA DRB1*11 and HLA DRB1*12 polymorphisms in dengue cases and their susceptibilities in the development of dengue in a population in Ouagadougou, Burkina Faso. Methodology: This was a case-control study involving 56 patients with clinically and biologically confirmed dengue fever and 65 others who had never been in contact with DENV, for a total of 121 individuals. A blood sample was taken from each study participant. After extraction of genomic DNA using the salting-out technique, characterisation of carriage of the HLA-DRB1*11 and 1*12 alleles was carried out using multiplex polymerase chain reaction (PCR). The χ² test, odds ratio (OR), and confidence interval (CI) were calculated using SPSS software to estimate associations and assess the level of risk. Results: Allele frequencies in the general population were 64.4% and 62.8% for HLA DRB1*11 and HLA DRB1*12, respectively. The HLA-DRB1*12 allele was present in 28.9% of cases and 33.9% of controls. The HLA-DRB1*11 allele was present in 32.2% of both cases and controls. In this study, no direct association was found between the presence of the HLA-DRB1*11 and HLA-DRB1*12 alleles and the surveillance of dengue infection. Furthermore, the absence of the HLA-DRB1*11 allele was associated with protection against the development of severe disease (OR = 0.03; 95% CI [0.11 - 0.80]; and p = 0.01). Conclusion: No risk of developing severe dengue fever was found in individuals carrying the HLA-DRB1*11 and HLA-DRB 1*12 alleles. However, further study of other HLA alleles involved in the development of severe dengue may provide more information.

Can a diet rich in Brassicaceae help control Helicobacter pylori infection? A systematic review

IntroductionHelicobacter pylori (Hp) infection is highly prevalent globally and poses a significant public health challenge due to its link with chronic gastritis, peptic ulcers, and gastric malignancies. Hp’s persistence within the gastric environment, particularly in case of infection with virulent strains, triggers chronic inflammatory responses and mucosal damage. Antibiotic therapy is the primary approach for Hp eradication, but antibiotic resistance and adverse effects hinder treatment efficacy. Emerging evidence suggests that Brassicaceae-derived metabolites could serve as adjunctive therapy for Hp infection, offering potential antimicrobial and anti-inflammatory benefits.MethodsA systematic literature review was conducted following PRISMA guidelines to assess the impact of Brassicaceae-rich diets on Hp infection control. Searches were performed in MEDLINE PubMed, Web of Science, and the Cochrane Library until 18 October 2023, without language or date restrictions. Eligible studies meeting PICOS criteria were included, encompassing populations infected with Hp or Hp-infected human cell cultures, interventions involving Brassicaceae consumption or its bioactive molecules, and outcomes related to Hp infection control, antibiotic therapy interactions, reduction of antibiotic side effects, and inflammation mitigation. Animal studies, cell line experiments, reviews unrelated to the research objectives, and studies on Hp-related gastric cancer were excluded.ResultsAvailable evidence indicates that Brassicaceae consumption exhibits the potential to reduce Hp colonization but achieving complete eradication of the pathogen remains challenging. Conflicting results regarding the efficacy of broccoli in Hp treatment emerge, with certain investigations suggesting limited effectiveness. Other studies point to a potential for heightened eradication rates when combined with standard triple therapy. Furthermore, promising outcomes are observed with broccoli extract supplements, indicating their role in mitigating Hp-induced gastric mucosal damage. In fact, it is noteworthy that sulforaphane and its derivatives manifest notable reductions in pro-inflammatory markers, indicative of their anti-inflammatory properties. Adverse events associated with antibiotic therapy seem unaffected by sulforaphane derivatives or probiotics. However, individual responses to these treatments vary, underscoring the unpredictability of their efficacy in ameliorating antibiotic therapy-related side effects.ConclusionOur systematic review highlights the potential of Brassicaceae-rich diets as adjunctive therapy for Hp infection, offering synergistic interactions with antibiotics and possibly mitigating antibiotic side effects and inflammation. Further research, particularly well-designed randomized trials, is warranted to elucidate the therapeutic efficacy and optimal utilization of Brassicaceae-derived metabolites in managing human Hp-related diseases.

Zebrafish navigating the metabolic maze: insights into human disease - assets, challenges and future implications.

Zebrafish (Danio rerio) have become indispensable models for advancing our understanding of multiple metabolic disorders such as obesity, diabetes mellitus, dyslipidemia, and metabolic syndrome. This review provides a comprehensive analysis of zebrafish as a powerful tool for dissecting the genetic and molecular mechanisms of these diseases, focusing on key genes, like pparγ, lepr, ins, and srebp. Zebrafish offer distinct advantages, including genetic tractability, optical transparency in early development, and the conservation of key metabolic pathways with humans. Studies have successfully used zebrafish to uncover conserved metabolic mechanisms, identify novel disease pathways, and facilitate high-throughput screening of potential therapeutic compounds. The review also highlights the novelty of using zebrafish to model multifactorial metabolic disorders, addressing challenges such as interspecies differences in metabolism and the complexity of human metabolic disease etiology. Moving forward, future research will benefit from integrating advanced omics technologies to map disease-specific molecular signatures, applying personalized medicine approaches to optimize treatments, and utilizing computational models to predict therapeutic outcomes. By embracing these innovative strategies, zebrafish research has the potential to revolutionize the diagnosis, treatment, and prevention of metabolic disorders, offering new avenues for translational applications. Continued interdisciplinary collaboration and investment in zebrafish-based studies will be crucial to fully harnessing their potential for advancing therapeutic development.

Liquid–liquid phase separation in neurodegenerative diseases: An updated understanding

Liquid&amp;ndash;liquid phase separation (LLPS), once understood merely as a physicochemical phenomenon, has emerged over the past decade as a critical player in life processes. LLPS provides a novel framework for understanding the structure, function, and spatiotemporal regulation of intracellular biomolecules. Through LLPS, biomolecules within cells can spontaneously assemble into membraneless compartments, which allow precise regulation of biochemical reactions and influence critical cellular processes such as signal transduction and gene expression. Despite its recognized significance in basic biological research, the role of LLPS in human disease is still an area worthy of continued exploration. Currently, the most studied disorders in relation to LLPS are neurodegenerative diseases and cancer. In neurodegenerative diseases, LLPS is closely linked to protein misfolding and aggregation, processes that can lead to the formation of toxic assemblies, ultimately causing neuronal damage and death. In cancer, aberrant LLPS may contribute to the dysregulation of signaling pathways, promoting uncontrolled cell proliferation and metastasis. This review highlights recent advances regarding the role of LLPS in the pathogenesis of neurodegenerative diseases, discussing its function in these pathological conditions and proposing directions for future research. As research progresses, the potential role of LLPS in other human diseases will likely be uncovered, offering new avenues for diagnosis and therapy. Therefore, further investigation into the mechanisms of LLPS and its involvement in disease pathology will be crucial for advancing our understanding of human health and disease.

A Shared Experience of Sciences and Mathematics Teaching during the Pandemic in the Philippines: Circumnavigating Challenges into Learning Opportunities and Communal Involvement

The far-reaching consequences of the novel human coronavirus disease 2019 (COVID-19) have brought unprecedented challenges across all aspects of human endeavors, including the resonating effects on educational systems worldwide. Learners and educators have showcased their adaptability in transforming traditional teaching methodologies into new strategies and modalities. This article outlines the collective efforts of the sciences and mathematics educators at the National University Philippines, and, in part, at Centro Escolar University, Manila in responding to the pressing need to innovate learning platforms and approaches during the pandemic. Moreover, this article describes the immediate effects of institutional policies and how resilience and preparedness transform challenges into opportunities. A reflection on integrating historical, social, and cultural lessons and dimensions into science and mathematics teaching to incorporate a sense of identity and to provide contextual and synchronizing examples to the concepts is also herein provided. Educators find strength in shared experiences and communal involvement during the pandemic to circumnavigate the struggles and difficulties, viewing them as opportunities and further elevating science and mathematics education using the lens of scientific, historical, and sociocultural inquiry.

NAILS: Normalized Artificial Intelligence Labeling Sensor for Self-Care Health

Visual examination of nails can reflect human health status. Diseases such as nutritive imbalances and skin diseases can be identified by looking at the colors around the plate part of the nails. We present the AI-based NAILS method to detect fingernails through segmentation and labeling. The NAILS leverages a pre-trained Convolutional Neural Network model to segment and label fingernail regions from fingernail images, normalizing RGB values to monitor tiny color changes via a GUI and the use of an HD webcam in real time. The use of normalized RGB values combined with AI-based segmentation for real-time health monitoring is novel and innovative. The NAILS algorithm could be used to self-extract and archive primary signs of diseases in humans, especially in rural areas or when other testing may be not available.

Establishment of a chronic biliary disease mouse model with cholecystoduodenal anastomosis for intestinal microbiome preservation.

Chronic biliary disease, including cholangitis and cholecystitis, is attributed to ascending infection by intestinal bacteria. Development of a mouse model for bile duct inflammation is imperative for the advancement of novel therapeutic approaches. Current models fail to replicate the harmful bacterial influx to the biliary tract observed in humans and spread of inflammation to the liver. Therefore, we aimed to establish an animal model of biliary disease that faithfully replicates the mechanisms of human diseases. To establish a cholecystoduodenal anastomosis model capable of mimicking the mechanisms of ascending infection and inflammation observed in human biliary diseases. We established a mouse biliary disease model by directly connecting the gallbladder and duodenum, enabling ascending infection into the biliary tract without traversing the sphincter of Oddi. In the cholecystoduodenal anastomosis mouse model, we observed impaired epithelial structure, wall thickening, and macrophage recruitment in the gallbladder. Despite the absence of postoperative antibiotics, we detected no changes in serum proinflammatory cytokine levels, indicating no systemic inflammation. Moreover, patency between the gallbladder and duodenum was confirmed via common bile duct ligation. Injection of patient-derived pathogenic bacteria into bile duct-ligated mice led to ascending infection, which significantly increased proinflammatory cytokine mRNA expression in the liver, duodenum, and ileum. These results indicate that our mouse model exhibited a direct connection between the gallbladder and duodenum, leading to ascending infection and closely mimicking the clinical features of biliary diseases observed in humans. The cholecystoduodenal anastomosis mouse model is an effective chronic biliary disease model with significant relevance in the development of microbiome-based therapies for the prevention and treatment of biliary disease.

Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease.

The gut microbiome plays a key role in bile acid (BA) metabolism, where a diversity of metabolic products contribute to human health and disease. In particular, Inflammatory Bowel Disease (IBD) is characterized by a low concentration of secondary bile acids (SBAs), whose transformation from primary bile acids (PBAs) is an essential function performed solely by gut bacteria. BA-transformation activity mediated by the bile acid inducible (bai) operon has been functionally characterized in the genus Clostridium, and homologous bai gene sequences have been found in metagenome-assembled genomes (MAGs) belonging to other taxa in the human gut, but it is unclear which species of bai-carrying bacteria perform physiologically significant amounts of bile acid transformation in healthy and sick individuals. Here, we analyzed hundreds of stool samples with paired metagenomic and metabolomic data from IBD patients and controls and found that the abundance of the bai operon in metagenomic samples was highly predictive of that sample's high- or low-SBA metabolic state. We further found that bai genes from the Clostridium species best characterized as BA transformers were more prevalent in IBD patients than in non-IBD controls, while bai genes from uncharacterized taxa known only from MAGs were much more physiologically relevant in non-IBD samples. These un-isolated clades of BA-transforming bacteria merit further research; as beyond their prevalence in the human population, we found some cases in which they engrafted in IBD patients who had undergone fecal microbiota transplantation and experienced a clinical response.IMPORTANCEIn this paper, we identify specific bacteria that perform an important metabolic function in the human gut and demonstrate that in the guts of a large subset of patients with IBD, these bacteria are missing and the function is defective. This is a rare example where the correlation between the absence of specific bacteria and the dysfunction of metabolism is directly observed, not in mice nor in the lab, but in physiologic microbial communities in the human gut. Our results point to a path for studying how a small but important set of bacteria is affected by conditions in the IBD gut and perhaps to the development of interventions to mitigate the loss of these bacteria in IBD.