Unravelling the modes of phototoxicity of NIR absorbing chlorophyll derivative in cancer cells under normoxic and hypoxic conditions.

The efficacy of photodynamic treatment (PDT) against deep-seated tumor is hindered by low penetration depth of light as well as hypoxic conditions which prevails in tumor. To overcome this limitation, Near-infrared (NIR) absorbing photosensitizers have been investigated actively. In the present study we evaluated the PDT efficacy of an NIR absorbing chlorophyll derivative 'Cycloimide Purpurin-18 (CIPp-18)' in Human Breast carcinoma (MCF-7) and cervical adenocarcinoma (Hela) cells under normoxic and hypoxic conditions.

Current and Emerging Therapies for Lysosomal Storage Disorders.

Lysosomal storage disorders (LSDs) are rare inherited metabolic disorders characterized by defects in the function of specific enzymes responsible for breaking down substrates within cellular organelles (lysosomes) essential for the processing of macromolecules. Undigested substrate accumulates within lysosomes, leading to cellular dysfunction, tissue damage, and clinical manifestations. Clinical features vary depending on the degree and type of enzyme deficiency, the type and extent of substrate accumulated, and the tissues affected.

State-of-the-Art Liver Cancer Organoids: Modeling Cancer Stem Cell Heterogeneity for Personalized Treatment.

Liver cancer poses a global health challenge with limited therapeutic options. Notably, the limited success of current therapies in patients with primary liver cancers (PLCs) may be attributed to the high heterogeneity of both hepatocellular carcinoma (HCCs) and intrahepatic cholangiocarcinoma (iCCAs). This heterogeneity evolves over time as tumor-initiating stem cells, or cancer stem cells (CSCs), undergo (epi)genetic alterations or encounter microenvironmental changes within the tumor microenvironment.

Backbone resonance assignments of PhoCl, a photocleavable protein.

PhoCl is a photocleavable protein engineered from a green-to-red photoconvertible fluorescent protein by circular permutation, and has been used in various optogenetic applications including precise control of protein localization and activity in cells. Upon violet light illumination, PhoCl undergoes a β-elimination reaction to be cleaved at the chromophore, resulting in spontaneous dissociation into a large empty barrel and a small C-terminal peptide. However, the structural determinants and the mechanism of the PhoCl photocleavage remain elusive, hindering the further development of more robust photocleavable optogenetic tools.

Molecular mechanism of osteoclast differentiation of PBMC in patients with rheumatoid arthritis.

Objective: Rheumatoid arthritis (RA) is an autoimmune condition that causes severe joint deformities and impaired functionality, affecting the well-being and daily life of individuals. Consequently, there is a pressing demand for identifying viable therapeutic targets for treating RA. This study aimed to explore the molecular mechanisms of osteoclast differentiation in PBMC from patients with RA through transcriptome sequencing and bioinformatics analysis.

Adaptation and validation of a tool for the quality assessment of genetic counseling in Brazil: perspectives from clinical geneticists.

In 2018, Portuguese researchers proposed the "Tool for Quality Assessment of Genetic Counseling," a 5-point Likert scale comprising 50 items across five dimensions, designed to assess genetic counseling from the professional's perspective. This descriptive, cross-sectional study aimed to adapt this tool to Brazilian Portuguese, validate it among Brazilian clinical geneticists, and conduct a preliminary assessment of the quality of genetic counseling in Brazil. The adaptation process involved expert-driven content validation and calculation of the Content Validity Index (CVI) to ensure equivalence between the original and adapted versions.

Substrate stiffness dictates unique doxorubicin-induced senescence-associated secretory phenotypes and transcriptomic signatures in human pulmonary fibroblasts.

Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood.

Role of immune cell homeostasis in research and treatment response in hepatocellular carcinoma.

Introduction Recently, immune cells within the tumor microenvironment (TME) have become crucial in regulating cancer progression and treatment responses. The dynamic interactions between tumors and immune cells are emerging as a promising strategy to activate the host's immune system against various cancers. The development and progression of hepatocellular carcinoma (HCC) involve complex biological processes, with the role of the TME and tumor phenotypes still not fully understood.

Are rs1042059 and rs11591377 polymorphisms of BMI1 gene related to leukemia?

Introduction: Hematologic malignancies, originating from uncontrolled growth of hematopoietic and lymphoid tissues, constitute 6.5% of all cancers worldwide. Various risk factors including genetic disorders and single nucleotide polymorphisms play a role in the pathogenesis of hematologic malignancies.

Defective Mammary Epithelial Outgrowth in Transgenic EKAREV-NLS Mice: Correction via Estrogen Supplementation and Genetic Background Modification.

Fluorescent biosensors offer a powerful tool for tracking and quantifying protein activity in living systems with high temporospatial resolution. However, the expression of genetically encoded fluorescent proteins can interfere with endogenous signaling pathways, potentially leading to developmental and physiological abnormalities. The EKAREV-NLS mouse model, which carries a FRET-based biosensor for monitoring extracellular signal-regulated kinase (ERK) activity, has been widely utilized both in vivo and in vitro across various cell types and organs.

The tumor immune microenvironment in primary cutaneous melanoma.

Melanoma is an immunogenic tumor. The melanoma tumor immune microenvironment (TIME) is made up of a heterogenous mix of both immune and non-immune cells as well as a multitude of signaling molecules. The interactions between tumor cells, immune cells and signaling molecules affect tumor progression and therapeutic responses.

Ritlecitinib, a JAK3 /TEC inhibitor, modulates the markers of celiac autoimmunity in alopecia areata and vitiligo patients.

Background: Celiac disease (CeD) has shown an association with autoimmune disorders including vitiligo and alopecia areata (AA). Ritlecitinib, a JAK3 and TEC kinase family inhibitor, has been approved for treatment of patients with AA and is in late-stage development for vitiligo. Ritlecitinib inhibits cytotoxic T cells, NK cells, and B cells which play a role in the pathogenesis of CeD.

Palmitate potentiates the SMAD3-PAI-1 pathway by reducing nuclear GDF15 levels.

Nuclear growth differentiation factor 15 (GDF15) reduces the binding of the mothers' against decapentaplegic homolog (SMAD) complex to its DNA-binding elements. However, the stimuli that control this process are unknown. Here, we examined whether saturated fatty acids (FA), particularly palmitate, regulate nuclear GDF15 levels and the activation of the SMAD3 pathway in human skeletal myotubes and mouse skeletal muscle, where most insulin-stimulated glucose use occurs in the whole organism.

Evidence for Multiple Independent Expansions of Fox Gene Families Within Flatworms.

Expansion and losses of gene families are important drivers of molecular evolution. A recent survey of Fox genes in flatworms revealed that this superfamily of multifunctional transcription factors, present in all animals, underwent extensive losses and expansions during platyhelminth evolution. In this paper, I analyzed Fox gene complement in four additional species of platyhelminths, that represent early-branching lineages in the flatworm phylogeny: catenulids (Stenostomum brevipharyngium and Stenostomum leucops) and macrostomorphs (Macrostomum hystrix and Macrostomum cliftonense).

Kineococcus halophytocola sp. nov., Isolated from Leaves of Halophyte Sesuvium portulacastrum L.

An aerobic, Gram-stain-positive, motile, coccus-shaped actinomycete, designated strain LSe6-4, was isolated from leaves of sea purslane (Sesuvium portulacastrum L.) in Thailand and subjected to a polyphasic taxonomic studies. Growth of the strain occurred at temperatures between 15 and 38 °C, and with NaCl concentrations 0-13%.

Epigenome-wide association study of perceived discrimination in the Multi-Ethnic Study of Atherosclerosis (MESA).

Perceived discrimination, recognized as a chronic psychosocial stressor, has adverse consequences on health. DNA methylation (DNAm) may be a potential mechanism by which stressors get embedded into the human body at the molecular level and subsequently affect health outcomes. However, relatively little is known about the effects of perceived discrimination on DNAm.

The transmembrane protein TMEM196 controls cell proliferation and determines the floor plate cell lineage.

The neural tube, the embryonic precursor to the vertebrate central nervous system, comprises distinct progenitor and neuronal domains, each with specific proliferation programs. In this study, we identified TMEM196, a novel transmembrane protein that plays a crucial role in regulating cell proliferation in the floor plate in chick embryos. TMEM196 is expressed in the floor plate, and its overexpression leads to reduced cell proliferation without affecting the pattern formation of the neural tube.

Ultrasmall Au-GRHa Nanosystem for FL/CT Dual-Mode Imaging-Guided Targeting Photothermal Therapy of Ovarian Cancer.

As the most common and lethal cancer of the female gonads, ovarian cancer (OC) has a grave impact on people's health. OC is asymptomatic, insidious in onset, difficult to diagnose and treat, fast-growing, and easy to metastasize and has poor prognosis and high mortality. How to detect OC as early as possible and treat it without side effects has become a challenging medical problem.

Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway.

Acetaminophen induced acute liver injury (ALI) has a high incidence and is a serious medical problem, but there is a lack of effective treatment. The enterohepatic axis is one of the targets of recent attention due to its important role in liver diseases. Disulfiram (DSF) is a multitarget drug that has been proven to play a role in a variety of liver diseases and can affect intestinal flora, but whether it can alleviate ALI is not clear.

Pancreatic stellate cell: Update on molecular investigations and clinical translation in pancreatic cancer.

Pancreatic cancer is a particularly aggressive tumor, distinguished by the presence of a prominent collagenous stroma and desmoplasia that envelops the tumor cells. Pancreatic stellate cell (PSC) contributes to the formation of a dense fibrotic stroma and has been demonstrated to facilitate tumor progression. As the significance of PSCs is increasingly revealed, more explorations are focused on the complex molecular mechanisms and tumor-stromal crosstalk in order to guide potential therapeutic approaches through deactivating or reprogramming PSCs.

Easily Water-Synthesisable Iron-Chloranilate Frameworks as High Energy and High-Power Cathodes for Sustainable Alkali-Ion Batteries.

Achieving high battery performance from low-cost, easily synthesisable electrode materials is crucial for advancing energy storage technologies. Metal organic frameworks (MOFs) combining inexpensive transition metals and organic ligands are promising candidates for high-capacity cathodes. Iron-chloranilate-water frameworks are herein reported to be produced in aqueous media under mild conditions.

Multifunctional Mycobacterial Topoisomerases with Distinctive Features.

Tuberculosis (TB) continues to be a major cause of death worldwide despite having an effective combinatorial therapeutic regimen and vaccine. Being one of the most successful human pathogens, retains the ability to adapt to diverse intracellular and extracellular environments encountered by it during infection, persistence, and transmission. Designing and developing new therapeutic strategies to counter the emergence of multidrug-resistant and extensively drug-resistant TB remains a major task.

Lineage-dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and independent immunotherapeutic targets.

Background: Neuroblastoma is a heterogeneous disease with adrenergic (ADRN)- and therapy resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype and propose pan-neuroblastoma and cell state specific targetable cell-surface proteins.

Methods: We characterized cell lines, patient-derived xenografts, and patient samples as ADRN-dominant or MES-dominant to define subtype-specific and pan-neuroblastoma gene sets.

Localization of Cholecystokinin/Sulfakinin Neuropeptides in Biomphalaria glabrata, an Intermediate Host for Schistosomiasis.

Snails belonging to the genus Biomphalaria serve as obligatory intermediate hosts for the trematode Schistosoma mansoni, the causative agent for the most widespread form of schistosomiasis. The simpler nervous systems of gastropod molluscs, such as Biomphalaria, provide advantageous models for investigating neural responses to infection at the cellular and network levels. The present study examined neuropeptides related to cholecystokinin (CCK), a major multifunctional regulator of central nervous system (CNS) function in mammals.

Interplay of Light, Melatonin, and Circadian Genes in Skin Pigmentation Regulation.

Circadian regulation of skin pigmentation is essential for thermoregulation, ultraviolet (UV) protection, and synchronization of skin cell renewal. This regulation involves both cell-autonomous photic responses and non-cell-autonomous hormonal control, particularly through melatonin produced in a light-sensitive manner. Photosensitive opsins, cryptochromes, and melatonin regulate circadian rhythms in skin pigment cells.