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BACKGROUND: Ginseng Radix et Rhizoma (GS) is frequently used as an adjuvant therapy for patients with heart failure (HF). Metoprolol is widely used in patients with HF. However, there is no report on the combined effects of GS and metoprolol in patients with HF. OBJECTIVE: This study investigated the combined effects of GS and metoprolol in male C57BL/6J mice with HF and the underlying mechanisms. MATERIALS AND METHODS: We utilized a mouse myocardial HF model to measure the serum levels of creatine kinase (CK) and creatine kinase-MB form (CK-MB) using an automated biochemical analyzer. Lactate dehydrogenase (LDH) and cardiac troponin (cTnT) levels were determined using enzyme-linked immunosorbent assays. Autophagy of myocardial cells was evaluated using transmission electron microscopy, and changes in signal pathway proteins related to autophagy were analyzed by Western blotting. RESULTS: GS combined with metoprolol improved heart function, reduced heart damage, and decreased serum levels of CK, CK-MB, LDH, and cTnT. The combination of GS and metoprolol decreased autophagy in myocardial cells by reducing the levels of autophagy-related proteins (LC3, p62, Beclin1, and Atg5) and increasing the ratios of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR. CONCLUSION: GS enhanced the anti-heart failure effect of metoprolol. Its mechanism of action might be related to the inhibition of autophagy mediated by the activation of the PI3K/Akt/mTOR pathway.
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Autofagia , Insuficiência Cardíaca , Metoprolol , Camundongos Endogâmicos C57BL , Panax , Animais , Masculino , Autofagia/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/metabolismo , Metoprolol/farmacologia , Camundongos , Panax/química , Transdução de Sinais/efeitos dos fármacos , Doença Crônica , Rizoma/química , Modelos Animais de Doenças , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Extratos Vegetais/farmacologia , Creatina Quinase/sangue , Sinergismo Farmacológico , Creatina Quinase Forma MB/sangueRESUMO
Synthetic deer antler peptides (TSKYR, TSK, and YR) stimulate the proliferation of human chondrocytes and osteoblasts and increase the chondrocyte content of collagen and glycosamino-glycan in vitro. This study investigated the peptide mixture's pain relief and chondroprotective effect in a rat model of collagenase-induced osteoarthritis. Thirty-six adult male Sprague-Dawley rats were divided into three groups: control (saline), positive control (hyaluronic acid), and ex-perimental (peptides). Intra-articular collagenase injections were administered on days 1 and 4 to induce osteoarthritis in the left knees of the rats. Two injections of saline, hyaluronic acid, or the peptides were injected into the same knees of each corresponding group at the beginning of week one and two, respectively. Joint swelling, arthritic pain, and histopathological changes were evaluated. Injection of the peptides significantly reduced arthritic pain compared to the control group, as evidenced by the closer-to-normal weight-bearing and paw withdrawal threshold test results. Histological analyses showed reduced cartilage matrix loss and improved total cartilage degeneration score in the experimental versus the control group. Our findings suggest that intra-articular injection of synthetic deer antler peptides is a promising treatment for osteoarthritis.
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Chifres de Veado , Cervos , Modelos Animais de Doenças , Osteoartrite do Joelho , Peptídeos , Ratos Sprague-Dawley , Animais , Injeções Intra-Articulares , Chifres de Veado/química , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/induzido quimicamente , Masculino , Ratos , Peptídeos/administração & dosagem , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Ácido Hialurônico/administração & dosagem , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Cartilagem Articular/metabolismo , ColagenasesRESUMO
BACKGROUND: The clinical efficacy of Jinchuang Ointment, a traditional Chinese medicine (TCM), in treating chronic non-healing diabetic wounds has been demonstrated over the past decades. Both in vitro and in vivo angiogenic activities have been reported for its herbal ingredients, including dragon blood from the palm tree Daemonorops draco and catechu from Uncaria gambir Roxb. Additionally, crude extracts of dragon blood have exhibited hypoglycemic effects not only in animal studies but also in cell-based in vitro assays. RESULTS: Our findings indicate that crude dragon blood extract promotes the differentiation of myoblasts into myotubes. Partially purified fractions of dragon blood crude extract significantly enhance the expression of muscle cell differentiation-related genes such as myoG, myoD, and myoHC. Our results also demonstrate that crude extracts of dragon blood can inhibit platelet-derived growth factor-induced PAI-1 expression in primary rat vascular smooth muscle cells, thereby favoring changes in hemostasis towards fibrinolysis. Consistent with previous reports, reduced expression of plasminogen activator inhibitor 1 (PAI-1) accelerates wound healing. However, further separation resulted in a significant loss of both activities, indicating the involvement of more than one compound in these processes. Stem cells play a crucial role in muscle injury repair. Neither dragon blood nor catechu alone stimulated the proliferation of human telomerase reverse transcriptase (hTERT)-immortalized and umbilical cord mesenchymal stem cells. Interestingly, the proliferation of both types of stem cells was observed when crude extracts of dragon blood and catechu were present together in the stem cell growth medium. CONCLUSIONS: Dragon blood from D. draco offers multifaceted therapeutic benefits for treating chronic nonhealing diabetic wounds from various perspectives. Most drugs in Western medicine consist of small molecules with defined ingredients. However, this is not the case in TCM, as the activities of dragon blood reported in this study. Surprisingly, the activities documented here align with descriptions in ancient Chinese medical texts dating back to A.D. 1625.
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PROPOSE: To evaluate the advantage of the manual adaptive plans comparing to the scheduled plans, and explored clinical factors predicting patients suitable for adaptive strategy. METHODS AND MATERIALS: Eighty two patients with weekly online cone-beam computed tomography (CBCT) were enrolled. The re-CT simulation was performed after 15 fractions and a manual adaptive plan was developed if a significant deviation of the planning target volume (PTV) was found. To evaluate the dosimetric benefit, D98, homogeneity index (HI) and conformity index (CI) for the planning target volume (PTV), as well as D2cc of the bowel, bladder, sigmoid and rectum were compared between manual adaptive plans and scheduled ones. The clinical factors influencing target motion during radiotherapy were analyzed by chi-square test and logistic regression analysis. RESULTS: The CI and HI of the manual adaptive plans were significantly superior to the scheduled ones (P = 0.0002, 0.003, respectively), demonstrating a better dose coverage of the target volume. Compared to the scheduled plans, D98 of the manual adaptive plans increased by 3.3% (P = 0.0002), the average of D2cc to the rectum, bladder decreased 0.358 Gy (P = 0.000034) and 0.240 Gy (P = 0.03), respectively. In addition, the chi-square test demonstrated that age, primary tumor volume, and parametrial infiltration were the clinical factors influencing target motion during radiotherapy. Multivariate analysis further identified the large tumor volume (≥ 50cm3, OR = 3.254, P = 0.039) and parametrial infiltration (OR = 3.376, P = 0.018) as the independent risk factors. CONCLUSION: We found the most significant organ motion happened after 15 fractions during treatment. The manual adaptive plans improved the dose coverage and decreased the OAR doses. Patients with bulky mass or with parametrial infiltration were highly suggested to adaptive strategy during definitive radiotherapy due to the significant organ motion.
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Tomografia Computadorizada de Feixe Cônico , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Neoplasias do Colo do Útero , Humanos , Feminino , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Pessoa de Meia-Idade , Idoso , Adulto , Tomografia Computadorizada de Feixe Cônico/métodos , Radiometria/métodos , Órgãos em Risco/efeitos da radiação , Idoso de 80 Anos ou maisRESUMO
The placenta plays a crucial role in successful mammalian reproduction. Ruminant animals possess a semi-invasive placenta characterized by a highly vascularized structure formed by maternal endometrial caruncles and fetal placental cotyledons, essential for full-term fetal development. The cow placenta harbors at least two trophoblast cell populations: uninucleate (UNC) and binucleate (BNC) cells. However, the limited capacity to elucidate the transcriptomic dynamics of the placental natural environment has resulted in a poor understanding of both the molecular and cellular interactions between trophoblast cells and niches, and the molecular mechanisms governing trophoblast differentiation and functionalization. To fill this knowledge gap, we employed Stereo-seq to map spatial gene expression patterns at near single-cell resolution in the cow placenta at 90 and 130 days of gestation, attaining high-resolution, spatially resolved gene expression profiles. Based on clustering and cell marker gene expression analyses, key transcription factors, including YBX1 and NPAS2, were shown to regulate the heterogeneity of trophoblast cell subpopulations. Cell communication and trajectory analysis provided a framework for understanding cell-cell interactions and the differentiation of trophoblasts into BNCs in the placental microenvironment. Differential analysis of cell trajectories identified a set of genes involved in regulation of trophoblast differentiation. Additionally, spatial modules and co-variant genes that help shape specific tissue structures were identified. Together, these findings provide foundational insights into important biological pathways critical to the placental development and function in cows.
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Perfilação da Expressão Gênica , Placenta , Placentação , Transcriptoma , Animais , Bovinos/genética , Feminino , Gravidez , Placenta/metabolismo , Trofoblastos/metabolismoRESUMO
BACKGROUND: Canine mammary tumors (CMTs) in intact female dogs provide a natural model for investigating metastatic human cancers. Our prior research identified elevated expression of Anterior Gradient 2 (AGR2), a protein disulfide isomerase (PDI) primarily found in the endoplasmic reticulum (ER), in CMT tissues, highly associated with CMT progression. We further demonstrated that increased AGR2 expression actively influences the extracellular microenvironment, promoting chemotaxis in CMT cells. Unraveling the underlying mechanisms is crucial for assessing the potential of therapeutically targeting AGR2 as a strategy to inhibit a pro-metastatic microenvironment and impede tumor metastasis. METHODS: To identify the AGR2-modulated secretome, we employed proteomics analysis of the conditioned media (CM) from two CMT cell lines ectopically expressing AGR2, compared with corresponding vector-expressing controls. AGR2-regulated release of 14-3-3ε (gene: YWHAE) and α-actinin 4 (gene: ACTN4) was validated through ectopic expression, knockdown, and knockout of the AGR2 gene in CMT cells. Extracellular vesicles derived from CMT cells were isolated using either differential ultracentrifugation or size exclusion chromatography. The roles of 14-3-3ε and α-actinin 4 in the chemotaxis driven by the AGR2-modulated CM were investigated through gene knockdown, antibody-mediated interference, and recombinant protein supplement. Furthermore, the clinical relevance of the release of 14-3-3ε and α-actinin 4 was assessed using CMT tissue-immersed saline and sera from CMT-afflicted dogs. RESULTS: Proteomics analysis of the AGR2-modulated secretome revealed increased abundance in 14-3-3ε and α-actinin 4. Ectopic expression of AGR2 significantly increased the release of 14-3-3ε and α-actinin 4 in the CM. Conversely, knockdown or knockout of AGR2 expression remarkably reduced their release. Silencing 14-3-3ε or α-actinin 4 expression diminished the chemotaxis driven by AGR2-modulated CM. Furthermore, AGR2 controls the release of 14-3-3ε and α-actinin 4 primarily via non-vesicular routes, responding to the endoplasmic reticulum (ER) stress and autophagy activation. Knockout of AGR2 resulted in increased α-actinin 4 accumulation and impaired 14-3-3ε translocation in autophagosomes. Depletion of extracellular 14-3-3ε or α-actinin 4 reduced the chemotaxis driven by AGR2-modulated CM, whereas supplement with recombinant 14-3-3ε in the CM enhanced the CM-driven chemotaxis. Notably, elevated levels of 14-3-3ε or α-actinin 4 were observed in CMT tissue-immersed saline compared with paired non-tumor samples and in the sera of CMT dogs compared with healthy dogs. CONCLUSION: This study elucidates AGR2's pivotal role in orchestrating unconventional secretion of 14-3-3ε and α-actinin 4 from CMT cells, thereby contributing to paracrine-mediated chemotaxis. The insight into the intricate interplay between AGR2-involved ER stress, autophagy, and unconventional secretion provides a foundation for refining strategies aimed at impeding metastasis in both canine mammary tumors and potentially human cancers.
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Proteínas 14-3-3 , Actinina , Autofagia , Quimiotaxia , Estresse do Retículo Endoplasmático , Neoplasias Mamárias Animais , Mucoproteínas , Animais , Cães , Proteínas 14-3-3/metabolismo , Proteínas 14-3-3/genética , Feminino , Actinina/metabolismo , Actinina/genética , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/patologia , Linhagem Celular Tumoral , Quimiotaxia/genética , Autofagia/genética , Estresse do Retículo Endoplasmático/genética , Mucoproteínas/genética , Mucoproteínas/metabolismo , Proteínas Oncogênicas/metabolismo , Proteínas Oncogênicas/genéticaRESUMO
Emerging evidence shows that FAT atypical cadherin 1 (FAT1) mutations occur in lymphoma and are associated with poorer overall survival. Considering that diffuse large B cell lymphoma (DLBCL) is the category of lymphoma with the highest incidence rate, this study aims to explore the role of FAT1 in DLBCL. The findings demonstrate that FAT1 inhibits the proliferation of DLBCL cell lines by downregulating the expression of YAP1 rather than by altering its cellular localization. Mechanistic analysis via meRIP-qPCR/luciferase reporter assays showed that FAT1 increases the m6A modification of YAP1 mRNA 3'UTR and the subsequent binding of heterogeneous nuclear ribonucleoprotein D (HNRNPD) to the m6A modified YAP1 mRNA, thus decreasing the stability of YAP1 mRNA. Furthermore, FAT1 increases YAP1 mRNA 3'UTR m6A modification by decreasing the activity of the TGFß-Smad2/3 pathway and the subsequent expression of ALKBH5, which is regulated at the transcriptional level by Smad2/3. Collectively, these results reveal that FAT1 inhibits the proliferation of DLBCL cells by increasing the m6A modification of the YAP1 mRNA 3'UTR via the TGFß-Smad2/3-ALKBH5 pathway. The findings of this study therefore indicate that FAT1 exerts anti-tumor effects in DLBCL and may represent a novel target in the treatment of this form of lymphoma.
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Regiões 3' não Traduzidas , Proteínas Adaptadoras de Transdução de Sinal , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Linfoma Difuso de Grandes Células B , RNA Mensageiro , Fatores de Transcrição , Proteínas de Sinalização YAP , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Proteínas de Sinalização YAP/metabolismo , Proteínas de Sinalização YAP/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Linhagem Celular Tumoral , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Caderinas/metabolismo , Caderinas/genética , Adenosina/metabolismo , Adenosina/análogos & derivados , Transdução de SinaisRESUMO
Orally administered "tortoiseshell and deer antler gelatin" is a common traditional medicine for patients with osteoporosis or osteoarthritis. From the pepsin-digested gelatin, we previously isolated and identified the osteoblast-stimulating pentapeptide, TSKYR. Its trypsin digestion products include the dipeptide YR, enhancing calcium ion uptake, and tripeptide TSK, resulting in remarkable 30- and 50-fold increases in mineralized nodule area and density in human osteoblast cells. These peptides were chemically synthesized in this study. The composition of deer antler preparations comprises not only proteins and peptides but also a significant quantity of metal ion salts. By analyzing osteoblast growth in the presence of peptide YR and various metal ions, we observed a synergistic effect of calcium and strontium on the effects of YR. Those peptides could also stimulate the growth of C2C12 skeletal muscle cells and human chondrocytes, increasing collagen and glycosaminoglycan content in a three-dimensional environment. The maintenance of bone homeostasis relies on a balance between osteoclasts and osteoblasts. Deer antler peptides were observed to inhibit osteoclast differentiation, as evidenced by ROS generation, tartrate-resistant acid phosphatase (TRACP) activity assays, and gene expression in RAW264.7 cells. In summary, our findings provide a deep understanding of the efficacy of this folk medicine.
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Serviço Hospitalar de Emergência , Medição da Dor , Humanos , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , AdultoRESUMO
Spectrum-structure correlation is playing an increasingly crucial role in spectral analysis and has undergone significant development in recent decades. With the advancement of spectrometers, the high-throughput detection triggers the explosive growth of spectral data, and the research extension from small molecules to biomolecules accompanies massive chemical space. Facing the evolving landscape of spectrum-structure correlation, conventional chemometrics becomes ill-equipped, and deep learning assisted chemometrics rapidly emerges as a flourishing approach with superior ability of extracting latent features and making precise predictions. In this review, the molecular and spectral representations and fundamental knowledge of deep learning are first introduced. We then summarize the development of how deep learning assist to establish the correlation between spectrum and molecular structure in the recent 5 years, by empowering spectral prediction (i.e., forward structure-spectrum correlation) and further enabling library matching and de novo molecular generation (i.e., inverse spectrum-structure correlation). Finally, we highlight the most important open issues persisted with corresponding potential solutions. With the fast development of deep learning, it is expected to see ultimate solution of establishing spectrum-structure correlation soon, which would trigger substantial development of various disciplines.
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The objective of this study was to investigate the protective effect of Crataegus pinnatifida polysaccharide (CPP) on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice. The findings demonstrated that CPP improved free fatty acid (FFA)-induced lipid accumulation in HepG2 cells and effectively reduced liver steatosis and epididymal fat weight in NAFLD mice, as well as decreased serum levels of TG, TC, AST, ALT, and LDL-C. Furthermore, CPP exhibited inhibitory effects on the expression of fatty acid synthesis genes FASN and ACC while activating the expression of fatty acid oxidation genes CPT1A and PPARα. Additionally, CPP reversed disturbances in intestinal microbiota composition caused by HFD consumption. CPP decreased the firmicutes/Bacteroidetes ratio, increased Akkermansia abundance, and elevated levels of total short-chain fatty acid (SCFA) content specifically butyric acid and acetic acid. Our results concluded that CPP may intervene in the development of NAFLD by regulating of intes-tinal microbiota imbalance and SCFAs production. Our study highlights that CPP has a potential to modulate lipid-related pathways via alterations to gut microbiome composition thereby ex-erting inhibitory effects on obesity and NAFLD development.
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Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel procedure for major resection in patients with insufficient future liver remnant (FLR). Effective FLR augmentation is pivotal in the completion of ALPPS. Liver fibrosis/cirrhosis associated with chronic viral hepatitis impairs liver regeneration. To investigate the augmentation of FLR in associating ALPPS between patients with fibrotic/cirrhotic livers (FL) and non-fibrotic livers (NFL) and compare their short-term clinical outcomes and long-term survival. Patients were divided into two groups based on the Ishak modified staging: non-fibrotic liver group (NFL, stage 0) and fibrotic/cirrhotic liver group (FL, stage 1-5/6). Weekly liver regeneration in FLR, perioperative data, and survival outcomes were investigated. Twenty-seven patients with liver tumors underwent ALPPS (NFL, n = 7; FL, n = 20). NFL and FL patients had viral hepatitis (28.6% [n = 2] and 95% [n = 19]), absolute FLR volume increments of 134.90 ml and 161.85 ml (p = 0.825), and rates of hypertrophy were 16.46 ml/day and 13.66 ml/day (p = 0.507), respectively. In the FL group, baseline FLR volume was 360.13 ml, postoperatively it increased to a plateau (542.30 ml) in week 2 and declined (378.45 ml) in week 3. One patient (3.7%) with cirrhotic liver (stage 6) failed to proceed to ALPPS-II. The overall ALPPS-related major complication rate was 7.4%. ALPPS is feasible for fibrotic liver patients classified by Ishak modified stages ≤ 5. After ALPPS-I, 14 days for FLR augmentation seems an appropriate waiting time to reach a maximum FLR volume in these patients.
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Hepatectomia , Cirrose Hepática , Neoplasias Hepáticas , Regeneração Hepática , Veia Porta , Humanos , Hepatectomia/métodos , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Masculino , Feminino , Veia Porta/cirurgia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Pessoa de Meia-Idade , Ligadura/métodos , Idoso , Resultado do Tratamento , Fatores de Tempo , Fígado/cirurgia , Fígado/patologia , Adulto , Estudos RetrospectivosRESUMO
BACKGROUND & AIMS: Hepatocyte apoptosis, a well-defined form of cell death in non-alcoholic steatohepatitis (NASH), is considered the primary cause of liver inflammation and fibrosis. However, the mechanisms underlying the regulation of hepatocyte apoptosis in NASH remain largely unclear. We explored the anti-apoptotic effect of hepatocyte CD1d in NASH. METHODS: Hepatocyte CD1d expression was analyzed in patients with NASH and mouse models. Hepatocyte-specific gene overexpression or knockdown and anti-CD1d crosslinking were used to investigate the anti-apoptotic effect of hepatocyte CD1d on lipotoxicity-, Fas-, and concanavalin (ConA)-mediated liver injuries. A high-fat diet, a methionine-choline-deficient diet, a Fas agonist, and ConA were used to induce lipotoxic and/or apoptotic liver injuries. Palmitic acid was used to mimic lipotoxicity-induced apoptosis in vitro. RESULTS: We identified a dramatic decrease in CD1d expression in hepatocytes of patients with NASH and mouse models. Hepatocyte-specific CD1d overexpression and knockdown experiments collectively demonstrated that hepatocyte CD1d protected against hepatocyte apoptosis and alleviated hepatic inflammation and injuries in NASH mice. Furthermore, decreased JAK2-STAT3 signaling was observed in NASH patient livers. Mechanistically, anti-CD1d crosslinking on hepatocytes induced tyrosine phosphorylation of the CD1d cytoplasmic tail, leading to the recruitment and phosphorylation of JAK2. Phosphorylated JAK2 activated STAT3 and subsequently reduced apoptosis in hepatocytes, which was associated with an increase in anti-apoptotic effectors (Bcl-xL and Mcl-1) and a decrease in pro-apoptotic effectors (cleaved-caspase 3/7). Moreover, anti-CD1d crosslinking effectively protected against Fas- or ConA-mediated hepatocyte apoptosis and liver injury in mice. CONCLUSIONS: Our study uncovered a previously unrecognized anti-apoptotic CD1d-JAK2-STAT3 axis in hepatocytes that conferred hepatoprotection and highlighted the potential of hepatocyte CD1d-directed therapy for liver injury and fibrosis in NASH, as well as in other liver diseases associated with hepatocyte apoptosis. IMPACT AND IMPLICATIONS: Excessive and/or sustained hepatocyte apoptosis is critical in driving liver inflammation and injury. The mechanisms underlying the regulation of hepatocyte apoptosis in non-alcoholic steatohepatitis (NASH) remain largely unclear. Here, we found that CD1d expression in hepatocytes substantially decreases and negatively correlates with the severity of liver injury in patients with NASH. We further revealed a previously unrecognized anti-apoptotic CD1d-JAK2-STAT3 signaling axis in hepatocytes, which confers significant protection against liver injury in NASH and acute liver diseases. Thus, hepatocyte CD1d-targeted therapy could be a promising strategy to manipulate liver injury in both NASH and other hepatocyte apoptosis-related liver diseases.
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Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Camundongos , Apoptose , Concanavalina A , Modelos Animais de Doenças , Hepatócitos , InflamaçãoRESUMO
BACKGROUND: Dragon blood is a red fruit resin from the palm tree Daemonorops draco and is a herbal ingredient used in the traditional Chinese medicine, "Jinchuang Ointment," which is used to treat non-healing diabetic wounds. According to the Taiwan Herbal Pharmacopeia, the dracorhodin content in dragon blood should exceed 1.0%. RESULTS: Our findings indicate that dracorhodin and dragon blood crude extracts can stimulate glucose uptake in mouse muscle cells (C2C12) and primary rat aortic smooth muscle cells (RSMC). Dracorhodin is not the only active compound in dragon blood crude extracts from D. draco. Next, we orally administered crude dragon blood extracts to male B6 mice. The experimental group displayed a decreasing trend in fasting blood glucose levels from the second to tenth week. In summary, crude extracts of dragon blood from D. draco demonstrated in vivo hypoglycemic effects in B6 male mice. CONCLUSIONS: We provide a scientific basis "Jinchuang ointment" in treating non-healing wounds in patients with diabetes.
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BACKGROUND: Effective stroke rehabilitation requires high-dose, repetitive-task training, especially during the early recovery phase. However, the usability of upper-limb rehabilitation technology in acute and subacute stroke survivors remains relatively unexplored. In this study, we introduce subacute stroke survivors to MyoGuide, a mobile training platform that employs surface electromyography (sEMG)-guided neurofeedback training that specifically targets wrist extension. Notably, the study emphasizes evaluating the platform's usability within clinical contexts. METHODS: Seven subacute post-stroke patients (1 female, mean age 53.7 years, mean time post-stroke 58.9 days, mean duration per training session 48.9 min) and three therapists (one for eligibility screening, two for conducting training) participated in the study. Participants underwent ten days of supervised one-on-one wrist extension training with MyoGuide, which encompassed calibration, stability assessment, and dynamic tasks. All training records including the Level of Difficulty (LoD) and Stability Assessment Scores were recorded within the application. Usability was assessed through the System Usability Scale (SUS) and participants' willingness to continue home-based training was gauged through a self-developed survey post-training. Therapists also documented the daily performance of participants and the extent of support required. RESULTS: The usability analysis yielded positive results, with a median SUS score of 82.5. Compared to the first session, participants significantly improved their performance at the final session as indicated by both the Stability Assessment Scores (p = 0.010, mean = 229.43, CI = [25.74-433.11]) and the LoD (p < 0.001; mean: 45.43, CI: [25.56-65.29]). The rate of progression differed based on the initial impairment levels of the patient. After training, participants expressed a keen interest in continuing home-based training. However, they also acknowledged challenges related to independently using the Myo armband and software. CONCLUSIONS: This study introduces the MyoGuide training platform and demonstrates its usability in a clinical setting for stroke rehabilitation, with the assistance of a therapist. The findings support the potential of MyoGuide for wrist extension training in patients across a wide range of impairment levels. However, certain usability challenges, such as donning/doffing the armband and navigating the application, need to be addressed to enable independent MyoGuide training requiring only minimal supervision by a therapist.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Feminino , Pessoa de Meia-Idade , Punho , Reabilitação do Acidente Vascular Cerebral/métodos , Extremidade Superior , Articulação do PunhoRESUMO
Background: Traditional observational studies have found a possible risk association of the gut microbiota for psoriasis. Meanwhile, psoriasis may also affect the changes in the gut microbiota. However, the available evidence does not demonstrate a reciprocal relationship between the gut microbiota and psoriasis. This limits our understanding on the role of the gut microbiota in the mechanisms of psoriasis. Methods: To address this question we used Mendelian randomization, a novel epidemiological approach, and acquired the largest current gut microbiota GWAS data from the MiBioGen consortium as well as psoriasis GWAS data from the FinnGen consortium, and performed two-sample bidirectional MR analyses using a multiple MR analysis approach. Finally, the robustness of the results was assessed by sensitivity analysis. Results: Our results indicate that five bacterial genera are causally related to psoriasis and psoriasis is causally related to four bacterial genera. Conclusion: These results suggest a bidirectional causal influence of psoriasis on the gut microbiota. Our results somewhat challenge the causal inferences of previous observational studies. We found that the specific bacterial genera with a risk effect on psoriasis were different from those found to characterize psoriasis in previous observational studies, and that these psoriasis-characterizing genera were inversely associated with psoriasis.
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The frequency and intensity of heatwaves are increasing around the world, causing severe damages to plants, but whether leaf thermal metrics is in line with leaf economic spectrum is still controversial. Here, we measured leaf damage ratio, leaf thermal metrics (tolerance and sensitivity) and economic traits of 131 woody species across five cities along the Yangtze River after a two-month natural extreme temperature event. We found that leaf thermal sensitivity but not thermal tolerance was correlated with leaf damage ratio, and the relationships between leaf thermal metrics and economic traits were weak, indicating that leaf thermal adaptation may be independent from leaf carbon construction. This study suggests a potential indicator for predicting plant survival under heatwaves, urging future research to explore more physiological traits to comprehensively understand plant heat responses and adaptations.
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Aclimatação , Folhas de Planta , Folhas de Planta/fisiologia , Temperatura , Plantas , Resposta ao Choque TérmicoRESUMO
In this study, a new polysaccharide (PSPJ) with specific molecular weight and monosaccharide compositions was isolated and purified from the water extract of Panacis Japonici Rhizoma (PJR). 16S rRNA analysis and untargeted metabolomic analysis were used to assess PSPJ's efficacy in averting non-alcoholic fatty liver disease (NAFLD). This study indicated that PSPJ significantly reduced liver fat accumulation, the increase in blood lipids and ALT caused by HFD, indicating that PSPJ can prevent NAFLD. We demonstrated through cell experiments that PSPJ does not directly affect liver cells. The gut microbiota disorder and alterations in short-chain fatty acids (SCFAs) induced by the high-fat diet (HFD) were ameliorated by PSPJ, as evidenced by the analysis of 16S rRNA. In particular, supplementing PSPJ reduced the abundance of Turicibacter, Dubosiella, and Staphylococcus, and increased the abundance of Bacteroides, Blautia, and Lactobacillus. Untargeted metabolomic analysis shows that PSPJ improves liver metabolic disorders by regulating arachidonic acid metabolism, carbohydrate digestion and absorption, fatty acid biosynthesis, fatty acid metabolism and retinol metabolism. The findings of our investigation indicate that PSPJ has the potential to modulate liver metabolism through alterations in the composition of intestinal bacteria, hence preventing NAFLD.
Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Panax , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Panax/metabolismo , Fígado/metabolismo , Ácidos Graxos Voláteis/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Emerging studies have shown that FAT atypical cadherin 1 (FAT1) and autophagy separately inhibits and promotes acute myeloid leukemia (AML) proliferation. However, it is unknown whether FAT1 were associated with autophagy in regulating AML proliferation. METHODS: AML cell lines, 6-week-old male nude mice and AML patient samples were used in this study. qPCR/Western blot and cell viability/3H-TdR incorporation assays were separately used to detect mRNA/protein levels and cell activity/proliferation. Luciferase reporter assay was used to examine gene promoter activity. Co-IP analysis was used to detect the binding of proteins. RESULTS: In this study, we for the first time demonstrated that FAT1 inhibited AML proliferation by decreasing AML autophagy level. Moreover, FAT1 weakened AML autophagy level via decreasing autophagy related 4B (ATG4B) expression. Mechanistically, we found that FAT1 reduced the phosphorylated and intranuclear SMAD family member 2/3 (smad2/3) protein levels, thus decreasing the activity of ATG4B gene promoter. Furthermore, we found that FAT1 competitively bound to TGF-ßR II which decreased the binding of TGF-ßR II to TGF-ßR I and the subsequent phosphorylation of TGF-ßR I, thus reducing the phosphorylation and intranuclear smad2/3. The experiments in nude mice showed that knockdown of FAT1 promoted AML autophagy and proliferation in vivo. CONCLUSIONS: Collectively, these results revealed that FAT1 downregulates ATG4B expression via inhibiting TGFß-smad2/3 signaling activity, thus decreasing the autophagy level and proliferation activity of AML cells. GENERAL SIGNIFICANCE: Our study suggested that the "FAT1-TGFß-smad2/3-ATG4B-autophagy" pathway may be a novel target for developing new targeted drugs to AML treatment.
Assuntos
Leucemia Mieloide Aguda , Fator de Crescimento Transformador beta , Camundongos , Animais , Humanos , Masculino , Camundongos Nus , Proliferação de Células , Fator de Crescimento Transformador beta/farmacologia , Leucemia Mieloide Aguda/genética , Autofagia , Caderinas , Proteínas Relacionadas à Autofagia/genética , Cisteína Endopeptidases/metabolismoRESUMO
BACKGROUND: Several techniques have been developed to reduce blood loss in liver resection. The half-Pringle and Pringle maneuvers are commonly used for inflow control. This study compared the outcomes of different inflow control techniques in laparoscopic subsegmentectomy. METHODS: From October 2010 to December 2020, a total of 362 laparoscopic liver resections were performed by a single surgeon (C.C. Yong) in our institute. We retrospectively enrolled 133 patients who underwent laparoscopic subsegmentectomy during the same period. Perioperative and long-term outcomes were analyzed. RESULTS: The 133 patients were divided into 3 groups: no inflow control (n = 49), half-Pringle maneuver (n = 46), and Pringle maneuver (n = 38). A lower proportion of patients with cirrhosis were included in the half-Pringle maneuver group (P = .02). Fewer patients in the half-Pringle maneuver group had undergone previous abdominal (P = .01) or liver (P = .02) surgery. The no inflow control group had more patients with tumors located in the anterolateral segments (P = .001). The no inflow control group had a shorter operation time (P < .001) and less blood loss (P = .03). The need for blood transfusion, morbidity, and hospital days did not differ among the 3 groups. The overall survival did not significantly differ among the 3 groups (P = .89). CONCLUSIONS: The half-Pringle and Pringle maneuvers did not affect perioperative or long-term outcomes during laparoscopic subsegmentectomy. The inflow control maneuvers could be safely performed in laparoscopic subsegmentectomy.