RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Huachansu Capsule (HCSc) is a simple enteric-coated capsule refined from the skin of the dried toad, a traditional medicinal herb. It has been used clinically for many years to treat a variety of malignant tumors with remarkable efficacy. To date, a number of main components of HCSc have been reported to be cardiotoxic, but the specific mechanism of cardiotoxicity is still unknown. AIM OF THE STUDY: The aim of this study was to elucidate the possible cardiotoxic symptoms caused by high-doses of HCSc and to further reveal the complex mechanisms by which it causes cardiotoxicity. MATERIALS AND METHODS: UPLC-Q-Exactive Orbitrap MS and network toxicology were used to identify and predict the potential toxic components, related signaling pathways. Then, we used acute and sub-acute toxicity experiments to reveal the apparent phenomenon of HCSc-induced cardiotoxicity. Finally, we combined transcriptomics and metabolomics to elucidate the potential mechanism of action, and verified the putative mechanism by molecular docking, RT-qPCR, and Western blot. RESULTS: We found 8 toad bufadienolides components may be induced cardiac toxicity HCSc main toxic components. Through toxicity experiments, we found that high dose of HCSc could increase a variety of blood routine indexes, five cardiac enzymes, heart failure indexes (BNP), troponin (cTnI and cTnT), heart rate and the degree of heart tissue damage, while low-dose of HCSc had no such changes. In addition, by molecular docking, found that 8 kinds of main toxic components and cAMP, AMPK, IL1ß, mTOR all can be a very good combination, especially in the cAMP. Meanwhile, RT-qPCR and Western blot results showed that HCSc could induce cardiotoxicity by regulating a variety of heart-related differential genes and activating the cAMP signaling pathway. CONCLUSIONS: In this study, network toxicology, transcriptomics and metabolomics were used to elucidate the complex mechanism of possible cardiotoxicity induced by high-dose HCSc. Animal experiments, molecular docking, Western blot and RT-qPCR experiments were also used to verify the above mechanism. These findings will inform further mechanistic studies and provide theoretical support for its safe clinical application.

Assuntos

Cardiotoxicidade , Metabolômica , Transcriptoma , Animais , Metabolômica/métodos , Masculino , Transcriptoma/efeitos dos fármacos , Ratos , Bufanolídeos/toxicidade , Simulação de Acoplamento Molecular , Ratos Sprague-Dawley , Farmacologia em Rede , Cápsulas , Transdução de Sinais/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Anuros

RESUMO

Essential oil of Acorus tatarinowii Schott (ATEO) have significant biological activity, but their physical and chemical properties are unstable and susceptible to interference by external factors, resulting in oxidation, decomposition, and isomerization of essential oils (EOs), ultimately diminishing the quality of EOs and escalating clinical risks. In this research, based on the concept of " combination of medicine and adjuvant, " the unsuitable stabilizer Cinnabaris in Lingzhu powder prescription was modified with a SiO2 surface to become a stabilizer suitable for Pickering emulsion. The modified Cinnabaris was synthesized, with a focus on exploring the surface modification of Cinnabaris to facilitate its role as a stabilizer in Pickering emulsion. Thermal stability studies showed that modified Cinnabaris-stabilized emulsion had higher EOs retention and lower peroxide value and hydrogen peroxide content. GC-MS analysis showed that the volatile components in the emulsion were more stable than the EOs. In vitro dissolution experiments showed that in the dissolution medium of artificial gastric juice and artificial intestinal juice, compared with the ATEO, the release in Pickering emulsion was faster within 48 h, indicating that the ATEO had been encapsulated in Pickering emulsion, which could improve the in vitro dissolution rate of EOs. This study convincingly demonstrates the potential of modified Cinnabaris-stabilized Pickering emulsion to improve the thermal stability and in vitro dissolution rate of EOs.

RESUMO

The morphology of the choriocarcinomatous variant of cervical squamous cell carcinoma (SCC) suggests an undifferentiated aggressive biological behaviour and a poor outcome, for which standard treatment has not been established. In addition, cases are rarely reported, with only five cases of patients with cervical carcinoma with choriocarcinoma reported previously in the literature. This current case report describes in detail a patient who was diagnosed with cervical SCC mixed with choriocarcinomatous differentiation. The case report includes details of the diagnosis, pathology, short tandem repeat genotyping, treatment and follow-up of this patient. As there is no standard treatment for this variant, the patient underwent surgery followed by radiotherapy. Unfortunately, 4 months after therapy discontinuation, radiological evaluation and laboratory tests documented a recurrence of the disease and the patient died. This report also systematically reviews the literature on cervical cancer associated with choriocarcinomatous differentiation and the five previous cases. It provides the most up-to-date summary of this disease, including its clinical manifestations, histopathology, diagnosis, treatment and prognosis.

Assuntos

Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico , Diferenciação Celular , Pessoa de Meia-Idade , Coriocarcinoma/patologia , Coriocarcinoma/diagnóstico , Coriocarcinoma/cirurgia , Evolução Fatal , Adulto

RESUMO

Biomolecular condensates, such as the nucleolus, stress granules/processing bodies and germ granules, are multiphase assemblages whose formation mechanisms and significance remain poorly understood. Here we identify protein constituents of the spatiotemporally ordered P, Z and M multiphase condensates in Caenorhabditis elegans germ granules using optimized TurboID-mediated proximity biotin labelling. These include 462, 41 and 86 proteins localizing to P, Z and M condensates, respectively, of which 522 were previously unknown protein constituents. Each condensate's proteins are enriched for distinct classes of structured and intrinsically disordered domains, suggesting divergent functions and assembly mechanisms. Through a functional screen, we identify a germ granule protein, HERD-1, which prevents the mixing of P, Z and M condensates. Mixing in herd-1 mutants correlates with disorganization of germline small RNA pathways and prolonged epigenetic inheritance of RNA interference-induced gene silencing. Forced mixing of these condensate components using a nanobody with specific binding activity against green fluorescent protein also extends epigenetic inheritance. We propose that active maintenance of germ granule immiscibility helps to organize and regulate small RNA-driven transgenerational epigenetic inheritance in C. elegans.

RESUMO

Background: Cerebral ischaemia-reperfusion injury (CIRI) could worsen the inflammatory response and oxidative stress in brain tissue. According to previous studies, ferulic acid methyl ester (FAME), as the extract with the strongest comprehensive activity in the traditional Chinese medicine Huang Hua oil dot herb, has significant anti-oxidative stress and neuroprotective functions, and can effectively alleviate CIRI, but its mechanism of action is still unclear. Methods: Firstly, the pharmacological effects of FAME were investigated by in vitro oxidative stress and inflammatory experiments. Secondly, evaluate the therapeutic effects of FAME in the treatment of CIRI by brain histopathological staining and cerebral infarct area by replicating the in vivo MACO model. Thirdly, RNA-Seq and network pharmacology were utilized to predict the possible targets and mechanisms of FAME for CIRI at the molecular level. Finally, the expression of key target proteins, as well as the key regulatory relationships were verified by molecular docking visualization, Western Blotting and immunohistochemistry. Results: The results of in vitro experiments concluded that FAME could significantly reduce the content of TNF-α, IL-1ß and ROS, inhibiting COX-2 and iNOS protein expression in cells(p<0.01). FAME was demonstrated to have anti-oxidative stress and anti-inflammatory effects. The results of in vivo experiments showed that after the administration of FAME, the area of cerebral infarction in rats with CIRI was reduced, the content of Bcl-2 and VEGF was increased(p<0.05). Network pharmacology and RNA-Seq showed that the alleviation of CIRI by FAME may be through PI3K-AKT and HIF-1 signaling pathway. Enhanced expression of HIF-1α, VEGF, p-PI3K, p-AKT proteins in the brain tissues of rats in the FAME group was verified by molecular docking and Western Blotting. Conclusion: FAME possesses significant anti-inflammatory and anti-oxidative stress activities and alleviates CIRI through the PI3K/HIF-1α/VEGF signaling pathway.

RESUMO

BACKGROUND: Eczema, an inflammatory skin disease causing intense itching, is a function of a range of internal and external factors, impacting individuals of all ages and leading to economic loss. Inflammation is the most important manifestation of eczema, and Matricaria recutita essential oil (MREO) extracted from Matricaria recutita possesses excellent antibacterial and anti-inflammatory properties. METHODS: In this study, Matricaria recutita microemulsions were prepared by the trans-phase emulsification method and their stability was determined by evaluating the relevant indexes. Establishment of 2,4-dinitro-chlorobenzene-induced AD model in mice. Detection of serum indexes of IL-6, IL-17, and TNF-α, and on pathological tissue sections, the HE staining, toluidine blue staining, immunohistochemistry, and observation were performed. RESULTS: The study obtained optimal conditions for the preparation of microemulsion formulations of Matricaria recutita. Through quality evaluation, it was found that the microemulsion increased stability, reduced irritation, and retained anti-inflammatory activity and therapeutic effects on eczema compared to Matricaria recutita essential oil (MREO). Studies have demonstrated that microemulsion formulations of Matricaria recutita and Matricaria recutita significantly down regulate the proinflammatory factors TNF-α, IL-17, and IL-6. It was shown by hematoxylin-eosin (HE) staining that both Matricaria recutita essential oil (MREO) and Matricaria recutita microemulsion (MRME) improved the inflammatory status of eczematous skin tissues in mice. The number of mast cells expressed in the tissues was decreased in the surface-treated group, as shown by toluidine blue staining. Additionally, the number of mast cells expressed in the tissues in the surface-treated group was reduced, as demonstrated by immunohistochemistry. Furthermore, immunohistochemistry revealed that MREO and MRME have immunomodulatory effects on the tissues. CONCLUSION: The study showed that microemulsion formulations of Matricaria recutita may serve as a novel remedy for eczema.

RESUMO

The mechanisms underlying the development and progression of colon cancer are not fully understood. Herein, Src kinase associated phosphoprotein 1 (SKAP1), an immune cell adaptor, is identified as a novel colon cancer-related gene. SKAP1 expression is significantly increased in colon cancer cells. High SKAP1 levels are independently predictive of poor survival in patients with colon cancer. Notably, SKAP1 expression in colon cancer cells exerted a significant tumor-promoting effect in vivo rather than in vitro. Screening of tumor-infiltrating immune cells revealed the involvement of neutrophils in SKAP1-induced colon tumor promotion. Enhanced formation of neutrophil extracellular traps (NETs) is found to be a key downstream event that contributed to the pro-tumor role of SKAP1. In colon cancer cells, SKAP1 increased the expression of C-X-C motif chemokine ligand 8 (CXCL8) via nuclear factor of activated T cells c1 (NFATc1). The blockade of CXCL8 or NFATc1 largely attenuated neutrophil infiltration, NET formation, and tumor promotion induced by SKAP1. Furthermore, inhibiting SKAP1-induced NET significantly enhanced the antitumor efficiency of adoptive natural killer cell therapy in colon tumor models. In conclusion, SKAP1 significantly promotes colon cancer growth via the cancer cell/neutrophil NFATc1/CXCL8/NET axis, suggesting that SKAP1 is a potential target for colon cancer therapy.

RESUMO

BACKGROUND: Premature ovarian insufficiency (POI) is a condition characterized by a substantial decline or loss of ovarian function in women before the age of 40. However, the pathogenesis of POI remains to be further elucidated, and specific targeted drugs which could delay or reverse ovarian reserve decline are urgently needed. Abnormal DNA damage repair (DDR) and cell senescence in granulosa cells are pathogenic mechanisms of POI. Ubiquitin-specific protease 14 (USP14) is a key enzyme that regulates the deubiquitylation of DDR-related proteins, but whether USP14 participates in the pathogenesis of POI remains unclear. METHODS: We measured USP14 mRNA expression in granulosa cells from biochemical POI (bPOI) patients. In KGN cells, we used IU1 and siRNA-USP14 to specifically inhibit USP14 and constructed a cell line stably overexpressing USP14 to examine its effects on DDR function and cellular senescence in granulosa cells. Next, we explored the therapeutic potential of IU1 in POI mouse models induced by D-galactose. RESULTS: USP14 expression in the granulosa cells of bPOI patients was significantly upregulated. In KGN cells, IU1 treatment and siUSP14 transfection decreased etoposide-induced DNA damage levels, promoted DDR function, and inhibited cell senescence. USP14 overexpression increased DNA damage, impaired DDR function, and promoted cell senescence. Moreover, IU1 treatment and siUSP14 transfection increased nonhomologous end joining (NHEJ), upregulated RNF168, Ku70, and DDB1, and increased ubiquitinated DDB1 levels in KGN cells. Conversely, USP14 overexpression had the opposite effects. Intraperitoneal IU1 injection alleviated etoposide-induced DNA damage in granulosa cells, ameliorated the D-galactose-induced POI phenotype, promoted DDR, and inhibited cell senescence in ovarian granulosa cells in vivo. CONCLUSIONS: Upregulated USP14 in ovarian granulosa cells may play a role in POI pathogenesis, and targeting USP14 may be a potential POI treatment strategy. Our study provides new insights into the pathogenesis of POI and a novel POI treatment strategy.

Assuntos

Senescência Celular , Dano ao DNA , Reparo do DNA , Células da Granulosa , Insuficiência Ovariana Primária , Ubiquitina Tiolesterase , Feminino , Insuficiência Ovariana Primária/patologia , Insuficiência Ovariana Primária/metabolismo , Insuficiência Ovariana Primária/genética , Células da Granulosa/metabolismo , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/patologia , Senescência Celular/efeitos dos fármacos , Animais , Humanos , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/genética , Reparo do DNA/efeitos dos fármacos , Camundongos , Adulto , Camundongos Endogâmicos C57BL , Linhagem Celular

RESUMO

Inferring the interactions between genes is essential for understanding the mechanisms underlying biological processes. Gene networks will change along with the change of environment and state. The accumulation of gene expression data from multiple states makes it possible to estimate the gene networks in various states based on computational methods. However, most existing gene network inference methods focus on estimating a gene network from a single state, ignoring the similarities between networks in different but related states. Moreover, in addition to individual edges, similarities and differences between different networks may also be driven by hub genes. But existing network inference methods rarely consider hub genes, which affects the accuracy of network estimation. In this paper, we propose a novel node-based joint Gaussian copula graphical (NJGCG) model to infer multiple gene networks from gene expression data containing heterogeneous samples jointly. Our model can handle various gene expression data with missing values. Furthermore, a tree-structured group lasso penalty is designed to identify the common and specific hub genes in different gene networks. Simulation studies show that our proposed method outperforms other compared methods in all cases. We also apply NJGCG to infer the gene networks for different stages of differentiation in mouse embryonic stem cells and different subtypes of breast cancer, and explore changes in gene networks across different stages of differentiation or different subtypes of breast cancer. The common and specific hub genes in the estimated gene networks are closely related to stem cell differentiation processes and heterogeneity within breast cancers.

RESUMO

Coronary heart disease is a prevalent cardiovascular ailment globally, with myocardial infarction (MI) being one of its most severe manifestations. The morbidity and mortality of MI are escalating, showing an increasing trend among younger, highly educated individuals, thereby posing a serious threat to public health. Currently, thrombolysis, percutaneous coronary intervention, and coronary artery bypass grafting are the primary clinical treatments for MI. Although these methods significantly reduce patient mortality, complications often result in poor prognoses. Due to limitations in chemical synthetic drug research, the focus has shifted towards developing herbs based on natural substances. Natural medicines represent a novel approach for safer and more effective MI management and treatment. They can control multiple pathogenic variables by targeting various pathways and systems. This paper investigates the molecular mechanisms of MI and evaluates the application of natural products and medicinal plants in MI treatment over the past 5 years, demonstrating their specific good therapeutic potential and superior tolerance. These natural therapies have been shown to mitigate myocardial cell damage caused by MI through mechanisms such as oxidative stress, inflammation, apoptosis, angiogenesis, myocardial fibrosis, autophagy, endoplasmic reticulum stress, mitophagy, and pyroptosis. This review offers the latest insights into the application of natural products and medicinal plants in MI treatment, elucidating their mechanisms of action and serving as an important reference for MI prevention.

RESUMO

The unavoidable residual tumor tissue from surgery and the strong aggressiveness of tumor cells pose challenges to the postoperative treatment of tumor patients, accompanied by in situ tumor recurrence and decreased quality of life. Therefore, there is an urgent need to explore appropriate postoperative therapeutic strategies to remove residual tumor cells after surgery to inhibit tumor recurrence and metastasis after surgery. In recent years, with the rapid development of biomedical materials, the study of local delivery systems as postoperative delivery of therapeutic agents has gradually attracted the attention of researchers. Injectable in situ-forming hydrogel is a locally administered agent injected in situ as a solution that can be loaded with various therapeutic agents and rapidly gels to form a semi-solid gel at the treatment site. This type of hydrogel tightly fills the surgical site and covers irregular excision surfaces. In this paper, we review the recent advances in the application of injectable in situ-forming hydrogels in postoperative therapy, focusing on the matrix materials of this type of hydrogel and its application in the postoperative treatment of different types of tumors, as well as discussing the challenges and prospects of its clinical application.

Assuntos

Hidrogéis , Recidiva Local de Neoplasia , Humanos , Hidrogéis/química , Hidrogéis/administração & dosagem , Recidiva Local de Neoplasia/prevenção & controle , Animais , Injeções , Sistemas de Liberação de Medicamentos/métodos , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico

RESUMO

At present, chemotherapy combined with photodynamic therapy is exerting satisfactory therapeutic effects in the treatment of tumors. Chlorin e6 (Ce6) is a photosensitizer with high efficiency and low dark toxicity. At the same time, elemene (ELE) contains high-efficiency and low-toxicity anti-cancer active ingredients, which can effectively penetrate tumor tissue and inhibit its recovery and proliferation. Due to the poor water solubility of these two drugs, we prepared ELE/Ce6 co-loaded liposomes (Lipo-ELE/Ce6) to improve their water solubility, thereby enhancing the anti-tumor effect. The characterization of Lipo-ELE/Ce6 showed that Lipo-ELE/Ce6 had suitable encapsulation efficiency (EE), particle size, polydispersity (PDI), zeta potential, and good photo-controlled release properties. In vitro, Lipo-ELE/Ce6 effectively inhibited the growth of T24 cells and induced apoptosis, and more importantly, in vivo experiments showed that Lipo-ELE/Ce6 had significant anti-tumor effects, which was significantly better than free drugs. The above results suggest that Lipo-ELE/Ce6 can significantly enhance the induction of apoptosis of non-muscle invasive bladder cancer (NMIBC) by light-controlled release and ROS response.

Assuntos

Apoptose , Clorofilídeos , Preparações de Ação Retardada , Lipossomos , Fármacos Fotossensibilizantes , Porfirinas , Espécies Reativas de Oxigênio , Apoptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Animais , Humanos , Linhagem Celular Tumoral , Porfirinas/farmacologia , Porfirinas/química , Porfirinas/administração & dosagem , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Fotoquimioterapia/métodos , Camundongos Nus , Camundongos , Liberação Controlada de Fármacos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Solubilidade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Neoplasias não Músculo Invasivas da Bexiga

RESUMO

BACKGROUND: In total hip arthroplasty (THA), the positioning of components holds critical importance for factors such as joint stability, polyethylene liner wear, and range of motion. This meta-analysis aimed to compare the effects of intraoperative fluoroscopy (IF) versus no use of IF on component positioning and the restoration of patient anatomy during THA. METHODS: We conducted our systematic review following the recommendations outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The literature search was performed from the inception of medical databases up to August 2023. PubMed, Embase, Web of Science, Cochrane Controlled Trials Register, Cochrane Library, Highwire, Wanfang, China National Knowledge Infrastructure (CNKI), China Biology Medicine Disc (CBM), and China Science and Technology Journal (CSTD) databases were systematically searched to identify relevant studies comparing IF versus no IF during primary THA. RESULTS: Thirteen studies involving 2195 patients (2207 hips) were incorporated in the Analysis. No statistically significant differences were observed between the groups in terms of acetabular cup inclination angle (ACIA, P = .9), ACIA within the safe zone rate (P = .87), acetabular cup anteversion angle (ACAA, P = .42), ACAA within the safe zone rate (P = .35), combined safe zone rate (P = .30), limb length difference (LLD, P = .13), dislocation rate (P = .76), and infection rate (P = .97). In comparison to the no fluoroscopy group, the IF group exhibited prolonged operation time (P < .00001) and reduced femoral component offset difference (FCOD, P = .03). CONCLUSION: IF did not demonstrate improvements in acetabular cup placement, limb length difference, or dislocation occurrence. Nonetheless, IF showed a significant enhancement in restoring femoral offset. It is noteworthy that surgeons operating in facilities with lower patient volumes may observe more pronounced benefits from IF.

Assuntos

Acetábulo , Artroplastia de Quadril , Humanos , Artroplastia de Quadril/métodos , Fluoroscopia/métodos , Acetábulo/cirurgia , Acetábulo/diagnóstico por imagem , Prótese de Quadril

RESUMO

Early pregnancy loss (EPL) is a common event in human reproduction and is classified into histological subtypes such as hydropic abortion (HA) and hydatidiform moles (HMs), including complete hydatidiform moles (CHMs) and partial hydatidiform moles (PHMs). However, accurate diagnosis and improved patient management remain challenging due to high rates of misdiagnosis and diverse prognostic risks. Therefore, diagnostic biomarkers for EPL are urgently needed. Our study aimed to identify biomarkers for EPL through comprehensive proteomic analysis. Ten CHMs, six PHMs, ten HAs and ten normal control (NC) products of conception (POC) were used to obtain a proteomic portrait. Parallel reaction monitoring (PRM)-targeted proteomic and regression analyses were used to verify and select the diagnostic signatures. Finally, 14 proteins were selected and a panel of diagnostic classifiers (DLK1, SPTB/COL21A1, and SAR1A) was built to represent the CHM, PHM, and NC groups (auROC=0.900, 0.804/0.885, and 0.991, respectively). This high diagnostic power was further validated in another independent cohort (n = 148) by immunohistochemistry (IHC) (n = 120) and western blot (WB) analyses (n = 28). The protein SPTB was selected for further biological behaviour experiments in vitro. Our data suggest that SPTB maintains trophoblast cell proliferation, angiogenesis, cell motility and the cytoskeleton network. This study provides a comprehensive proteomic portrait and identifies potential diagnostic biomarkers. These findings enhance our understanding of EPL pathogenesis and offer novel targets for diagnosis and therapeutic interventions.

RESUMO

Inherited deficiency of zinc finger NFX1-type containing 1 (ZNFX1), a dsRNA virus sensor, is associated with severe familial immunodeficiency, multisystem inflammatory disease, increased susceptibility to viruses, and early mortality. However, limited treatments for patients with pathological variants of ZNFX1 exist due to an incomplete understanding of the diseases resulting from ZNFX1 mutations. Here, we demonstrate that ZNFX1 specifically inhibits the activation of the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome in response to NLRP3 activators both in vitro and in vivo. ZNFX1 retains NLRP3 in the cytoplasm and prevents its accumulation in the TGN38 + /TGN46+ vesicles in the resting state. Upon NLRP3 inflammasome activation, ZNFX1 is cleaved by caspase-1, establishing a feed-forward loop that promotes NLRP3 accumulation in the trans-Golgi network (TGN) and amplifies the activity of the downstream cascade. Expression of wild-type ZNFX1, but not of ZNFX1 with human pathogenic mutations, rescues the impairment of NLRP3 inflammasome inhibition. Our findings reveal a dual role of ZNFX1 in virus sensing and suppression of inflammation, which may become valuable for the development of treatments for ZNFX1 mutation-related diseases.

RESUMO

Houttuynia cordata Thunb, also known as "Chinese medicine antibiotic", is a medicine food homology plant. It has functions of clearing heat, eliminating toxins, in folk medicine. The extraction purification and bioactivity of Houttuynia cordata polysaccharides (HCPs) have been of wide interest to researchers in recent years studies. Studies have confirmed that HCPs exhibit various biofunctionalities, such as anti-inflammatory, antiviral, antibacterial, antioxidant, immunomodulatory, regulation of gut microbiota, and gut-lung axis, as well as anti-radiation, and anti-cancer properties. Therefore, a comprehensive systematic review is needed to summarize the recent advances of HCPs and facilitate a better understanding of their biofunctionalities. This paper reviews the research progress of HCPs in extraction and purification methods, chemical structures, biological activities, possible mechanisms of action, and potential application prospects, which can provide some valuable insights and updated information for their further development and application of HCPs in the fields of therapeutic agents, functional foods, cosmetics, animal feeds.

RESUMO

OBJECTIVE: To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). METHODS: From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. RESULTS: Compared with the HC group, the BD-I patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex. A significant interaction between the CACNA1C genotype and the cortical thickness of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted. Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex predominantly among carriers of the BD-I G allele. CONCLUSION: The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Assuntos

Atenção , Transtorno Bipolar , Canais de Cálcio Tipo L , Genótipo , Humanos , Adulto , Transtorno Bipolar/genética , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/diagnóstico por imagem , Masculino , Feminino , Canais de Cálcio Tipo L/genética , Imageamento por Ressonância Magnética , Córtex Cerebral/diagnóstico por imagem , Polimorfismo de Nucleotídeo Único , Pessoa de Meia-Idade , Adulto Jovem

RESUMO

Endogenous retroviruses (ERVs) occupy a significant part of the human genome, with some encoding proteins that influence the immune system or regulate cell-cell fusion in early extra-embryonic development. However, whether ERV-derived proteins regulate somatic development is unknown. Here, we report a somatic developmental function for the primate-specific ERVH48-1 (SUPYN/Suppressyn). ERVH48-1 encodes a fragment of a viral envelope that is expressed during early embryonic development. Loss of ERVH48-1 led to impaired mesoderm and cardiomyocyte commitment and diverted cells to an ectoderm-like fate. Mechanistically, ERVH48-1 is localized to sub-cellular membrane compartments through a functional N-terminal signal peptide and binds to the WNT antagonist SFRP2 to promote its polyubiquitination and degradation, thus limiting SFRP2 secretion and blocking repression of WNT/ß-catenin signaling. Knockdown of SFRP2 or expression of a chimeric SFRP2 with the ERVH48-1 signal peptide rescued cardiomyocyte differentiation. This study demonstrates how ERVH48-1 modulates WNT/ß-catenin signaling and cell type commitment in somatic development.

Assuntos

Diferenciação Celular , Retrovirus Endógenos , Proteínas de Membrana , Miócitos Cardíacos , Via de Sinalização Wnt , Humanos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/citologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Retrovirus Endógenos/metabolismo , Retrovirus Endógenos/genética , Animais , Proteínas do Envelope Viral/metabolismo , Proteínas do Envelope Viral/genética , Primatas , Células HEK293 , Mesoderma/metabolismo

RESUMO

BACKGROUND: Alström syndrome (ALMS), a rare recessively inherited ciliopathy caused by mutations in ALMS1, is characterized by retinal dystrophy, childhood obesity, sensorineural hearing loss, and type 2 diabetes mellitus. The majority of pathogenic variants in ALMS1 are nonsense and frameshift mutations, which would lead to premature protein truncation, whereas copy number variants are seldom reported. METHODS: Herein, we present a 10-year-old Chinese girl with ALMS. The potential causative genetic variant was confirmed through whole genome sequencing, quantitative real-time PCR analysis, and Sanger sequencing. Additionally, breakpoint analysis was performed to determine the exact breakpoint site of the large deletion and elucidate its probable formation mechanism. RESULTS: The patient had a cor triatriatum sinister (CTS) structure. Genetic analysis identified novel compound heterozygous variants in the patient, consisting of a frameshift variant c.4414_4415delGT (p.V1472Nfs*26) in ALMS1 and a novel large deletion at chr2:73,612,355-73,626,339, which encompasses exon 1 of the ALMS1 gene. Moreover, breakpoint analysis revealed that the large deletion probably formed through the microhomology-mediated end joining (MMEJ) mechanism due to the 6-bp microhomologies (TCCTTC) observed at both ends of the breakpoints. CONCLUSIONS: In this study, novel compound heterozygous variants in the ALMS1 gene were identified in an ALMS patient with a CTS structure. The molecular confirmation of these variants expands the mutational spectrum of ALMS1, while the manifestation of ALMS in the patient provides additional clinical insights into this syndrome.

Assuntos

Síndrome de Alstrom , Proteínas de Ciclo Celular , Mutação da Fase de Leitura , Heterozigoto , Sequenciamento Completo do Genoma , Criança , Feminino , Humanos , Síndrome de Alstrom/genética , Proteínas de Ciclo Celular/genética , Sequenciamento Completo do Genoma/métodos

RESUMO

A validated marker system is crucial to running an effective genomics-assisted breeding program. We used 36 Kompetitive Allele-Specific PCR (KASP) markers to genotype 376 clones from the biofortified cassava pipeline, and fingerprinted 93 of these clones with DArTseq markers to characterize breeding materials and evaluate their relationships. The discriminating ability of the 36-quality control (QC) KASP and 6602 DArTseq markers was assessed using 92 clones genotyped in both assays. In addition, trait-specific markers were used to determine the presence or absence of target genomic regions. Hierarchical clustering identified two major groups, and the clusters were consistent with the breeding program origins. There was moderate genetic differentiation and a low degree of variation between the identified groups. The general structure of the population was similar using both assays. Nevertheless, KASP markers had poor resolution when it came to differentiating the genotypes by seed sources and overestimated the prevalence of duplicates. The trait-linked markers did not achieve optimal performance as all markers displayed variable levels of false positive and/or false negative. These findings represent the initial step in the application of genomics-assisted breeding for the biofortified cassava pipeline, and will guide the use of genomic selection in the future.