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International Journal of Molecular... May 2024Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in family members have also been...
Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, -deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions.
Topics: Podocytes; Animals; Mice; Humans; Mice, Knockout; Doxorubicin; Cytoskeletal Proteins; Adaptor Proteins, Signal Transducing; Apoptosis; Nephrotic Syndrome; Male; Tumor Suppressor Proteins
PubMed: 38891998
DOI: 10.3390/ijms25115808 -
International Journal of Molecular... May 2024Anoikis, a form of apoptosis resulting from the loss of cell-extracellular matrix interaction, is a significant barrier to cancer cell metastasis. However, the...
Anoikis, a form of apoptosis resulting from the loss of cell-extracellular matrix interaction, is a significant barrier to cancer cell metastasis. However, the epigenetic regulation of this process remains to be explored. Here, we demonstrate that the histone deacetylase sirtuin 6 (SIRT6) plays a pivotal role in conferring anoikis resistance to colorectal cancer (CRC) cells. The protein level of SIRT6 is negatively correlated with anoikis in CRC cells. The overexpression of SIRT6 decreases while the knockdown of SIRT6 increases detachment-induced anoikis. Mechanistically, SIRT6 inhibits the transcription of N-myc downstream-regulated gene 1 (), a negative regulator of the AKT signaling pathway. We observed the up-regulation of SIRT6 in advanced-stage CRC samples. Together, our findings unveil a novel epigenetic program regulating the anoikis of CRC cells.
Topics: Humans; Anoikis; Colorectal Neoplasms; Sirtuins; Gene Expression Regulation, Neoplastic; Cell Cycle Proteins; Cell Line, Tumor; Intracellular Signaling Peptides and Proteins; Down-Regulation; Signal Transduction; Epigenesis, Genetic
PubMed: 38891773
DOI: 10.3390/ijms25115585 -
Polymers May 2024The immobilization of gold nanoparticle (AuNP) linear surface assemblies on polycarbonate (PC) melt surface via molding is investigated. The order of the particle...
The immobilization of gold nanoparticle (AuNP) linear surface assemblies on polycarbonate (PC) melt surface via molding is investigated. The order of the particle assemblies is preserved during the molding process. The assemblies on PC exhibit plasmonic coupling features and dichroic properties. The structure of the assemblies is quantified based on Scanning Electron Microscopy (SEM) and image analysis data using an orientational order parameter. The transfer process from mold to melt shows high structural fidelity. The order parameter of around 0.98 reflects the orientation of the lines and remains unaffected, independent of the injection direction of the melt relative to the particle lines. This is discussed in the frame of fountain flow during injection molding. The particles were permanently fixed and withstood the injection molding process, detachment of the substrate, and extraction in boiling ethanol. The plasmonic particles coupled strongly within the dense nanoparticle lines to produce anisotropic optical properties, as quantified by dichroic ratios of 0.28 and 0.52 using ultraviolet-visible-near-infrared (UV-Vis-NIR) spectroscopy. AuNP line assemblies on a polymer surface may be a basis for plasmonic devices like surface-enhanced Raman scattering (SERS) sensors or a precursor for nanowires. Their embedding via injection molding constitutes an important link between particle-self-assembly approaches for optically functional surfaces and polymer processing techniques.
PubMed: 38891499
DOI: 10.3390/polym16111553 -
Healthcare (Basel, Switzerland) May 2024This study examines mental health service providers who provided care to evacuees during the Israel-Hamas conflict. Utilizing a phenomenological qualitative method, the...
This study examines mental health service providers who provided care to evacuees during the Israel-Hamas conflict. Utilizing a phenomenological qualitative method, the research delves into the psychological impact on the participants' lived experiences. The sample included 25 mental health providers (13 female, age range 28-63, mean 42.4, SD 7.3; 15 psychologists and 10 social worker, average seniority 10.8 years, SD 5.2, range 2-18 years). Data were collected through semi-structured interviews conducted between December 2023 and March 2024. The data analysis revealed a dual narrative: Participants paid a major personal price and experienced secondary traumatization manifesting in emotional detachment, physical symptoms, and heightened arousal. They also derived a profound sense of meaning and fulfillment from their work, contributing to personal and professional growth. These findings underscore the complexity of their experiences, which were marked by the challenges of secondary trauma and the resilience fostered through their work. This study emphasizes the importance of support systems, including social and familial networks and professional supervision, in navigating these challenges. This study has several limitations, including small sample size and the use of virtual interviews, suggesting the need for further research with a broader participant base and in different contexts.
PubMed: 38891173
DOI: 10.3390/healthcare12111098 -
Cells May 2024The ability of human melanoma cells to switch from an epithelial to a mesenchymal phenotype contributes to the metastatic potential of disease. Metalloproteinases (MPs)...
The ability of human melanoma cells to switch from an epithelial to a mesenchymal phenotype contributes to the metastatic potential of disease. Metalloproteinases (MPs) are crucially involved in this process by promoting the detachment of tumor cells from the primary lesion and their migration to the vasculature. In gray horse melanoma, epithelial-mesenchymal transition (EMT) is poorly understood, prompting us to address MP expression in lesions versus intact skin by transcriptome analyses and the immunofluorescence staining (IF) of gray horse tumor tissue and primary melanoma cells. RNAseq revealed the deregulation of several MPs in gray horse melanoma and, notably, a 125-fold upregulation of matrix metalloproteinase 1 (MMP1) that was further confirmed by RT-qPCR from additional tumor material. The IF staining of melanoma tissue versus intact skin for MMP1 and tumor marker S100 revealed MMP1 expression in all lesions. The co-expression of S100 was observed at different extents, with some tumors scoring S100-negative. The IF staining of primary tumor cells explanted from the tumors for MMP1 showed that the metalloproteinase is uniformly expressed in the cytoplasm of 100% of tumor cells. Overall, the presented data point to MP expression being deregulated in gray horse melanoma, and suggest that MMP1 has an active role in gray horse melanoma by driving EMT-mediated tumor cell dissemination via the degradation of the extracellular matrix. Whilst S100 is considered a reliable tumor marker in human MM, gray horse melanomas do not seem to regularly express this protein.
Topics: Animals; Melanoma; Horses; Gene Expression Regulation, Neoplastic; Matrix Metalloproteinase 1; Epithelial-Mesenchymal Transition; Skin Neoplasms; Cell Line, Tumor; Metalloproteases; Humans
PubMed: 38891088
DOI: 10.3390/cells13110956 -
Communications Medicine Jun 2024Sepsis from infection is a global health priority and clinical trials have failed to deliver effective therapeutic interventions. To address complicating heterogeneity...
BACKGROUND
Sepsis from infection is a global health priority and clinical trials have failed to deliver effective therapeutic interventions. To address complicating heterogeneity in sepsis pathobiology, and improve outcomes, promising precision medicine approaches are helping identify disease endotypes, however, they require a more complete definition of sepsis subgroups.
METHODS
Here, we use RNA sequencing from peripheral blood to interrogate the host response to sepsis from participants in a global observational study carried out in West Africa, Southeast Asia, and North America (N = 494).
RESULTS
We identify four sepsis subtypes differentiated by 28-day mortality. A low mortality immunocompetent group is specified by features that describe the adaptive immune system. In contrast, the three high mortality groups show elevated clinical severity consistent with multiple organ dysfunction. The immunosuppressed group members show signs of a dysfunctional immune response, the acute-inflammation group is set apart by molecular features of the innate immune response, while the immunometabolic group is characterized by metabolic pathways such as heme biosynthesis.
CONCLUSIONS
Our analysis reveals details of molecular endotypes in sepsis that support immunotherapeutic interventions and identifies biomarkers that predict outcomes in these groups.
PubMed: 38890515
DOI: 10.1038/s43856-024-00542-7 -
Molecular Diagnosis & Therapy Jul 2024Apoptosis, or programmed cell death, maintains tissue homeostasis by eliminating damaged or unnecessary cells. However, cells can evade this process, contributing to... (Review)
Review
Apoptosis, or programmed cell death, maintains tissue homeostasis by eliminating damaged or unnecessary cells. However, cells can evade this process, contributing to conditions such as cancer. Escape mechanisms include anoikis, mitochondrial DNA depletion, cellular FLICE inhibitory protein (c-FLIP), endosomal sorting complexes required for transport (ESCRT), mitotic slippage, anastasis, and blebbishield formation. Anoikis, triggered by cell detachment from the extracellular matrix, is pivotal in cancer research due to its role in cellular survival and metastasis. Mitochondrial DNA depletion, associated with cellular dysfunction and diseases such as breast and prostate cancer, links to apoptosis resistance. The c-FLIP protein family, notably CFLAR, regulates cell death processes as a truncated caspase-8 form. The ESCRT complex aids apoptosis evasion by repairing intracellular damage through increased Ca2+ levels. Antimitotic agents induce mitotic arrest in cancer treatment but can lead to mitotic slippage and tetraploid cell formation. Anastasis allows cells to resist apoptosis induced by various triggers. Blebbishield formation suppresses apoptosis indirectly in cancer stem cells by transforming apoptotic cells into blebbishields. In conclusion, the future of apoptosis research offers exciting possibilities for innovative therapeutic approaches, enhanced diagnostic tools, and a deeper understanding of the complex biological processes that govern cell fate. Collaborative efforts across disciplines, including molecular biology, genetics, immunology, and bioinformatics, will be essential to realize these prospects and improve patient outcomes in diverse disease contexts.
Topics: Humans; Apoptosis; Neoplasms; Endosomal Sorting Complexes Required for Transport; Animals; CASP8 and FADD-Like Apoptosis Regulating Protein
PubMed: 38890247
DOI: 10.1007/s40291-024-00718-w -
Surgical Case Reports Jun 2024Gerbode defect is an unusual abnormal communication between the left ventricle and the right atrium and is a serious complication of aortic infective endocarditis. Group...
BACKGROUND
Gerbode defect is an unusual abnormal communication between the left ventricle and the right atrium and is a serious complication of aortic infective endocarditis. Group B Streptococcus is an uncommon cause of infective endocarditis and has a markedly destructive effect on valvular tissue. Acute fistulation between the left ventricle and the right atrium associated with this form of infective endocarditis is a life-threatening, aggressive complication that often requires urgent surgical intervention. However, the identification of actual communication is often extremely difficult. Herein, we describe an unusual case of Gerbode defect resulting from Group B Streptococcus infective endocarditis and discuss the issues surrounding such a rare cardiac defect and such an infection.
CASE PRESENTATION
A 60-year-old man with underlying uncontrolled diabetes mellitus underwent endoscopic retrograde biliary drainage for acute cholangitis. On the 10th postoperative day, the patient developed multiple acute cerebral embolisms. Transthoracic echocardiography demonstrated severe aortic regurgitation and a large mobile vegetation near the tricuspid annulus. No obvious fistula between the left ventricle and the right atrium could be demonstrated. The blood culture examination was positive for Group B Streptococcus. The patient was diagnosed with Group B Streptococcus infective endocarditis, and antibiotic therapy was initiated. Transesophageal echocardiogram performed after referral to our hospital confirmed detachment of the right coronary cusp of the aortic valve from the annulus and an abnormal cavity immediately below the right coronary cusp. Color Doppler imaging finally revealed systolic blood flows from the left ventricle into the right atrium through the cavity. Therefore, we diagnosed the patient with Gerbode defect resulting from Group B Streptococcus infective endocarditis. In addition to aortic valve replacement, defect closure and left ventricular outflow tract repair were successfully performed urgently for severely complicated and uncommon infective endocarditis. The patient was uneventfully discharged without any complications.
CONCLUSIONS
We reported successful surgical treatment of unusual active IE and Gerbode defect caused by GBS. Careful preoperative echocardiographic work-up is imperative for accurate early diagnosis and successful repair.
PubMed: 38890183
DOI: 10.1186/s40792-024-01943-5 -
Beilstein Journal of Nanotechnology 2024The mechanism by which insects achieve attachment and locomotion across diverse substrates has long intrigued scientists, prompting extensive research on the functional...
The mechanism by which insects achieve attachment and locomotion across diverse substrates has long intrigued scientists, prompting extensive research on the functional morphology of attachment pads. In stick insects, attachment and locomotion are facilitated by two distinct types of smooth cuticular attachment pads: the primary adhesion force-generating arolium and the friction force-generating euplantulae. They are both supported by an adhesive secretion delivered into the interspace between the attachment pads and the substrate. In this study, we analysed and compared internal morphology, material composition and ultrastructure, as well as the transportation pathways in both adhesive organs in the stick insect using scanning electron microscopy, micro-computed tomography, light microscopy, and confocal laser scanning microscopy. Our observations revealed structural differences between both attachment pads, reflecting their distinct functionality. Furthermore, our results delineate a potential pathway for adhesive secretions, originating from exocrine epidermal cells and traversing various layers before reaching the surface. Within the attachment pad, the fluid may influence the viscoelastic properties of the pad and control the attachment/detachment process. Understanding the material composition of attachment pads and the distribution process of the adhesive secretion can potentially aid in the development of more effective artificial attachment systems.
PubMed: 38887530
DOI: 10.3762/bjnano.15.52 -
BMC Ophthalmology Jun 2024
PubMed: 38886683
DOI: 10.1186/s12886-024-03525-3