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Lactate-derived histone lactylation is involved in multiple pathological processes through transcriptional regulation. The role of lactate-derived histone lactylation in the repair of spinal cord injury (SCI) remains unclear. Here we report that overall lactate levels and lactylation are upregulated in the spinal cord after SCI. Notably, H4K12la was significantly elevated in the microglia of the injured spinal cord, whereas exogenous lactate treatment further elevated H4K12la in microglia after SCI. Functionally, lactate treatment promoted microglial proliferation, scar formation, axon regeneration, and locomotor function recovery after SCI. Mechanically, lactate-mediated H4K12la elevation promoted PD-1 transcription in microglia, thereby facilitating SCI repair. Furthermore, a series of rescue experiments confirmed that a PD-1 inhibitor or microglia-specific AAV-sh-PD-1 significantly reversed the therapeutic effects of lactate following SCI. This study illustrates the function and mechanism of lactate/H4K12la/PD-1 signaling in microglia-mediated tissue repair and provides a novel target for SCI therapy.
Subject(s)
Histones , Lactic Acid , Microglia , Recovery of Function , Spinal Cord Injuries , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/pathology , Animals , Microglia/metabolism , Microglia/drug effects , Histones/metabolism , Recovery of Function/drug effects , Recovery of Function/physiology , Lactic Acid/metabolism , Rats , Lysine/metabolism , Lysine/analogs & derivatives , Lysine/pharmacology , Mice , Cicatrix/metabolism , Cicatrix/pathology , Female , Rats, Sprague-Dawley , Mice, Inbred C57BL , Male , Locomotion/drug effects , Locomotion/physiologyABSTRACT
CONTEXT: This study explores the interaction between particles in microplastic semi-coke water slurry at the molecular level using molecular simulation methods, specifically DFT calculations and MD simulations. In addition, the experiment of slurry preparation was carried out to study the viscosity and stability of the slurry. The electrostatic potential analysis shows that the interaction between microplastics and dispersant molecules occurs on atoms with large electronegativity or oxygen-containing functional groups, and the energy gap of frontier molecular orbitals indicated that PVC interacts most easily with the dispersant (0.39 eV), followed by PS (1.08 eV) and PET (3.65 eV). In addition, it is also noted that due to the steric hindrance effect, the adsorption energy was opposite to the DFT calculation results: PET was - 213.338 kcal/mol (NNO) which was highest, followed by PS (- 107.603 kcal/mol, NNO), and PVC (NNO) was lowest which was - 94.808 kcal/mol. And RDF shows similar results, which the probability of water molecules in the PET system was the highest, followed by PS, and finally, PVC. The MD results are consistent with the viscosity and stability characterization results of the slurry which PET has the lowest viscosity of 87.3 mPa·s. Finally, this study provides new ideas for the treatment of microplastics and the improvement of the performance of semi-coke water slurry and reveals the interaction mechanism between microplastics and semi-coke water slurry. METHODS: All calculations were performed using Materials Studio (MS) version 2020 software, BIOVIA Corporation. The DFT calculation was carried out through the DMol3 module. The DFT calculations include electron density, electrostatics, orbitals, and population analysis. In DMol3 module, the GGA-PBE function was selected to consider gradient changes in density in the simulated calculation. The DFT-D correction was selected, and all electrons were calculated by DNP for accurate core potentials and the DNP file was 4.4. MD simulation was performed through the Forcite module. MD simulation mainly focuses on relative concentration distribution analysis, radial distribution function, and adsorption energy calculation. All molecular geometry optimizations are performed in the Forcite module. In the molecular dynamic part, all simulations used PCFF forcefield. The NVT ensemble was adopted and using the Nosé thermostat.
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Sugarcane yellow leaf virus (SCYLV) can reduce sugarcane productivity. A novel detection system based on reverse transcription-multienzyme isothermal rapid amplification (RT-MIRA) combined with CRISPR-Cas12a, named RT-MIRA-CRISPR-Cas12a, was developed. This innovative approach employs crude leaf extract directly as the reaction template, streamlining the extraction process for simplicity and speed. Combining RT-MIRA and CRISPR-Cas12a in one reaction tube increases the ease of operation while reducing the risk of aerosol contamination. In addition, it exhibits sensitivity equivalent to qPCR, boasting a lower detection limit of 25 copies. Remarkably, the entire process, from sample extraction to reaction completion, requires only 52-57 minutes, just a thermostat water bath. The result can be observed and judged by the naked eye.IMPORTANCESugarcane yellow leaf disease (SCYLD) is an important viral disease that affects sugarcane yield. There is an urgent need for rapid, sensitive, and stable detection methods. The reverse transcription-multienzyme isothermal rapid amplification combined with CRISPR-Cas12a (RT-MIRA-CRISPR-Cas12a) method established in this study has good specificity and high sensitivity. In addition, the system showed good compatibility and stability with the crude leaf extract, as shown by the fact that the crude extract of the positive sample could still be stably detected after 1 week when placed at 4°C. RT-MIRA-CRISPR-Cas12a, reverse transcription polymerase chain reaction (RT-PCR), and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect SCYLV on 33 sugarcane leaf samples collected from the field, and it was found that the three methods reached consistent conclusions. This Cas12a-based detection method proves highly suitable for the rapid on-site detection of the SCYLV.
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Background: The aim of this study was to explore the association between lactate/albumin ratio and the prognosis of sepsis patients. Methods: A computerized search was performed in Pubmed, EMbase, Ovid, Medline, and Google Scholar to collate relevant studies. The results were compared using standardized mean differences (SMD)/odds ratio (OR) and 95% confidence intervals (CI). Prospective and retrospective cohort studies were both included in this study.
ABSTRACT
Wireless Power Transfer (WPT) has become a key technology to extend network lifetime in Wireless Rechargeable Sensor Networks (WRSNs). The traditional omnidirectional recharging method has a wider range of energy radiation, but it inevitably results in more energy waste. By contrast, the directional recharging mode enables most of the energy to be focused in a predetermined direction that achieves higher recharging efficiency. However, the MC (Mobile Charger) in this mode can only supply energy to a few nodes in each direction. Thus, how to set the location of staying points of the MC, its service sequence and its charging orientation are all important issues related to the benefit of energy replenishment. To address these problems, we propose a Fuzzy Logic-based Directional Charging (FLDC) scheme for Wireless Rechargeable Sensor Networks. Firstly, the network is divided into adjacent regular hexagonal grids which are exactly the charging regions for the MC. Then, with the help of a double-layer fuzzy logic system, a priority of nodes and grids is obtained that dynamically determines the trajectory of the MC during each round of service, i.e., the charging sequence. Next, the location of the MC's staying points is optimized to minimize the sum of charging distances between MC and nodes in the same grid. Finally, the discretized charging directions of the MC at each staying point are adjusted to further improve the charging efficiency. Simulation results show that FLDC performs well in both the charging benefit of nodes and the energy efficiency of the MC.
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PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment. CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.
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BACKGROUND: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and life-threatening autoimmune disease of the central nervous system. So far, only ten cases of PERM have been reported in children worldwide, including the one in this study. CASE PRESENTATION: We report a case of an 11-year-old boy with PERM with an initial presentation of abdominal pain, skin itching, dysuria, urinary retention, truncal and limb rigidity, spasms of the trunk and limbs during sleep, deep and peripheral sensory disturbances, and dysphagia. A tissue-based assay using peripheral blood was positive, demonstrated by fluorescent staining of mouse cerebellar sections. He showed gradual and persistent clinical improvement after immunotherapy with intravenous immunoglobulin, steroids, plasmapheresis and rituximab. CONCLUSIONS: We summarized the diagnosis and treatment of a patient with PERM and performed a literature review of pediatric PERM to raise awareness among pediatric neurologists. A better comprehension of this disease is required to improve its early diagnosis, treatment, and prognosis.
Subject(s)
Encephalomyelitis , Muscle Rigidity , Myoclonus , Humans , Male , Child , Muscle Rigidity/etiology , Encephalomyelitis/diagnosis , Encephalomyelitis/complications , Myoclonus/etiology , Myoclonus/diagnosisABSTRACT
Conductive hydrogels are pivotal for the advancement of flexible sensors, electronic skin, and healthcare monitoring systems, facilitating transformative innovations. However, issues such as inadequate intrinsic compatibility, mismatched mechanical properties, and limited stability curtail their potential, resulting in compromised device efficacy and performance degradation. In this research, we engineered functional hydrogels featuring a dual-crosslinked network composed of (PA/PVA)-P(AM-AA) to address these challenges. This design eliminates the need for conductive additives, thereby enhancing intrinsic compatibility. Notably, the hydrogels exhibit exceptional mechanical properties, with high tensile strength (â¼700 %), Young's modulus (â¼5.33 MPa), increased strength (â¼2.46 MPa) and toughness (â¼6.59 MJ m-3). They also achieve a compressive strength of â¼7.33 MPa at 80 % maximal compressive strain and maintain about 89 % transparency. Moreover, flexible sensors derived from these hydrogels demonstrate enhanced multimodal sensing capabilities, including temperature, strain, and pressure detection, enabling precise monitoring of human movements. The integration of multiple hydrogels into a three-dimensional sensor array facilitates detailed spatial pressure distribution mapping. By strategically applying dual-crosslinked network engineering and eliminating conductive additives, we have streamlined the design and manufacturing of hydrogels to meet the rising demand for high-performance wearable sensors.
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BACKGROUND: The therapeutic strategies for acute ischemic stroke were faced with substantial constraints, emphasizing the necessity to safeguard neuronal cells during cerebral ischemia to reduce neurological impairments and enhance recovery outcomes. Despite its potential as a neuroprotective agent in stroke treatment, Chikusetsu saponin IVa encounters numerous challenges in clinical application. RESULT: Brain-targeted liposomes modified with THRre peptides showed substantial uptake by bEnd. 3 and PC-12 cells and demonstrated the ability to cross an in vitro blood-brain barrier model, subsequently accumulating in PC-12 cells. In vivo, they could significantly accumulate in rat brain. Treatment with C-IVa-LPs-THRre notably reduced the expression of proteins in the P2RX7/NLRP3/Caspase-1 pathway and inflammatory factors. This was evidenced by decreased cerebral infarct size and improved neurological function in MCAO rats. CONCLUSION: The findings indicate that C-IVa-LPs-THRre could serve as a promising strategy for targeting cerebral ischemia. This approach enhances drug concentration in the brain, mitigates pyroptosis, and improves the neuroinflammatory response associated with stroke.
Subject(s)
Blood-Brain Barrier , Ischemic Stroke , Liposomes , Neuroprotective Agents , Pyroptosis , Rats, Sprague-Dawley , Saponins , Animals , Saponins/pharmacology , Saponins/chemistry , Pyroptosis/drug effects , Rats , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Liposomes/chemistry , Male , Ischemic Stroke/drug therapy , Ischemic Stroke/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , PC12 Cells , Oleanolic Acid/pharmacology , Oleanolic Acid/chemistry , Oleanolic Acid/analogs & derivatives , Brain/metabolism , Brain/drug effects , Peptides/chemistry , Peptides/pharmacology , Brain Ischemia/drug therapy , Brain Ischemia/metabolismABSTRACT
Enzyme-linked immunosorbent assay (ELISA) detects qualitatively and quantitatively the presence of antibodies or antigens in a sample. Due to its simplicity, high sensitivity, and user-friendliness, the test is widely used in laboratory research, clinical diagnoses, and food testing. This chapter describes the indirect semiquantitative ELISA protocol used to monitor antibody levels in animals and analyze the titer levels of specific antibodies against a target antigen in serum and saliva.
Subject(s)
Antibodies , Enzyme-Linked Immunosorbent Assay , Saliva , Enzyme-Linked Immunosorbent Assay/methods , Saliva/immunology , Animals , Antibodies/immunology , Antibodies/blood , Antigens/immunology , HumansABSTRACT
Alzheimer's disease (AD) is a fatal neurodegenerative disease in which senile plaques and neurofibrillary tangles are crucially involved in its physiological and pathophysiological processes. Growing animal and clinical studies have suggested that AD is also comorbid with some metabolic diseases, including type 2 diabetes mellitus (T2DM), and therefore, it is often considered brain diabetes. AD and T2DM share multiple molecular and biochemical mechanisms, including impaired insulin signaling, oxidative stress, gut microbiota dysbiosis, and mitochondrial dysfunction. In this review article, we mainly introduce oxidative stress and mitochondrial dysfunction and explain their role and the underlying molecular mechanism in T2DM and AD pathogenesis; then, according to the current literature, we comprehensively evaluate the possibility of regulating oxidative homeostasis and mitochondrial function as therapeutics against AD. Furthermore, considering dietary polyphenols' antioxidative and antidiabetic properties, the strategies for applying them as potential therapeutical interventions in patients with AD symptoms are assessed.
Subject(s)
Alzheimer Disease , Diabetes Mellitus, Type 2 , Mitochondria , Oxidative Stress , Polyphenols , Signal Transduction , Alzheimer Disease/metabolism , Alzheimer Disease/diet therapy , Alzheimer Disease/drug therapy , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/diet therapy , Oxidative Stress/drug effects , Humans , Polyphenols/pharmacology , Polyphenols/therapeutic use , Signal Transduction/drug effects , Signal Transduction/physiology , Animals , Mitochondria/metabolism , Mitochondria/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Antioxidants/therapeutic useABSTRACT
PM2.5 is a main atmospheric pollutant with various sources and complex chemical compositions, which are influenced by various factors, such as anthropogenic emissions (AE) and meteorological conditions (MC). MC have a significant impacts on variations in atmospheric pollutant; therefore, emission reduction policies and ambient air quality are non-linearly correlated, which hinders the accurate assessment of the effectiveness of control measures. In this study, we conducted online observations of PM2.5 and its chemical composition in Hohhot, China, from December 1, 2019, to February 29, 2020, to investigate how the chemical compositions of PM2.5 respond to the variations in AE and MC. Moreover, the random forest (RF) model was used to quantify the contributions of AE and MC to PM2.5 and its chemical composition during severe hazes and the COVID-19 pandemic lockdown period. During the clean period, MC reduced PM2.5 concentrations by 124%, while MC incresed PM2.5 concentrations by 49% during severe pollution episode. Inorganic aerosols (SO42-, NO3-, and NH4+) showed the strongest response to MC. MC significantly contributed to PM2.5 (36%), SO42- (32%), NO3- (29%), NH4+ (28%), OC (22%), and SOC (17%) levels during pollution episodes. From the pre-lockdown to lockdown period, AE (MC) contributed 52% (48%), 81% (19%), 48% (52%), 68% (32%), 59% (41%), and 288% (-188%) to the PM2.5, SO42-, NO3-, NH4+, OC, and SOC reductions, respectively. The variations in MC (especially the increase in relative humidity) rapidly generated meteorologically sensitive species (SO42-, NO3-, and NH4+), which led to severe winter pollution. This study provides a reference for assessing the net benefits of emission reduction measures for PM2.5 and its chemical compositions.
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Infection with Mycobacterium bovis precipitates a spectrum of pathologies in bovines, notably necrotic pneumonia, mastitis, and arthritis, impinging upon the health and nutritional assimilation of these animals. A pivotal factor, lipocalin 2 (Lcn2), is responsive to microbial invasion, inflammatory processes, and tissue damage, the extent of which Lcn2 modulates the gut environment, however, remains unclear in response to M. bovis-induced alterations. To explore the role of Lcn2 in shaping the gut milieu of mice during a 5-week period post-M. bovis infection, Lcn2 knockout Lcn2-/- mice were scrutinized for changes in the gut microbiota and metabolomic profiles. Results showed that Lcn2-/- mice infected with M. bovis exhibited notable shifts in the operational taxonomic units (OTUs) of gut microbiota, alongside significant disparities in α and ß diversity. Concomitantly, a marked increase was observed during the 5-week period in the abundance of Akkermansia, Oscillospira, and Bacteroides, coupled with a substantial decrease in Ruminococcus within the microbiome of Lcn2 knockout mice. Notably, Akkermansia muciniphila was significantly enriched in the gut flora of Lcn2-/- mice. Furthermore, the absence of Lcn2 significantly altered the gut metabolomic landscape, evidenced by elevated levels of metabolites such as taurodeoxycholic acid, 10-undecenoic acid, azelaic acid, and dodecanedioic acid in Lcn2-/- mice. Our findings demonstrated that the lack of Lcn2 in the context of M. bovis infection profoundly affected the regulation of gut microbiota and metabolomic components, culminating in a transformed gut environment. Our results revealed that Lcn2 may regulate gut microbiota and metabolome components, changing the intestinal environment, thereby affecting the infection status of M. bovis. IMPORTANCE: Our study addresses the critical knowledge gap regarding the specific influence of lipocalin 2 (LCN2) in the context of Mycobacterium bovis infection, particularly focusing on its role in the gut environment. Utilizing LCN2 knockout (Lcn2-/-) mice, we meticulously assessed changes in the gut microbiota and metabolic components following M. bovis infection. Our findings reveal alterations in the gut microbial community, emphasizing the potentially crucial role of LCN2 in maintaining stability. Furthermore, we observed significant shifts in specific microbial communities, including the enrichment of Akkermansia muciniphila, known for its positive impact on intestinal health and immune regulation. The implications of our study extend beyond understanding the dynamics of the gut microbiome, offering insights into the potential therapeutic strategies for gut-related health conditions and microbial dysbiosis.
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Ischemia-reperfusion injury (IRI) is a major event in renal transplantation, leading to adverse outcomes. Bone marrow mesenchymal stem cells (BMSCs) are novel promising therapeutics for repairing kidney injuries. The therapeutic efficacy of BMSCs with ISL1 overexpression in renal IRI and its underlying mechanism need to be investigated. The unilateral renal IRI rat model was established to mimic clinical acute kidney injury. Rats were injected with PBS, BMSCs-Scrambled or BMSCs-ISL1 via the tail vein at the timepoint of reperfusion, and then sacrificed after 24 h of reperfusion. The administration of BMSCs-ISL1 significantly improved renal function, inhibited tubular cells apoptosis, inflammation, oxidative stress in rats. In vitro, HKC cells subjected to H2O2 stimulation were pretreated with the conditioned medium (CM) of BMSCs-Scrambled or BMSCs-ISL1. The pretreatment of ISL1-CM attenuated apoptosis and oxidative stress induced by H2O2 in HKC cells. Our proteomic data suggested that haptoglobin (Hp) was one of the secretory proteins in ISL1-CM. Subsequent experiments confirmed that Hp was the important paracrine factor from BMSCs-ISL1 that exerted anti-apoptotic and antioxidant functions. Mechanistically, Hp played a cytoprotective role via the inhibition of ERK signaling pathway, which could be abrogated by Ro 67-7476, the ERK phosphorylation agonist. The results suggested that paracrine action may be the main mechanism for BMSCs-ISL1 to exert protective effects. As an important anti-apoptotic and antioxidant factor in ISL1-CM, Hp may serve as a new therapeutic agent for treating IRI, providing new insights for overcoming the long-term adverse effects of stem cell therapy.
Subject(s)
Apoptosis , LIM-Homeodomain Proteins , Mesenchymal Stem Cells , Oxidative Stress , Paracrine Communication , Reperfusion Injury , Transcription Factors , Animals , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Reperfusion Injury/therapy , Oxidative Stress/drug effects , Apoptosis/drug effects , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , LIM-Homeodomain Proteins/metabolism , LIM-Homeodomain Proteins/genetics , Rats , Male , Transcription Factors/metabolism , Transcription Factors/genetics , Rats, Sprague-Dawley , Kidney/metabolism , Kidney/pathology , Humans , Hydrogen Peroxide/pharmacology , Hydrogen Peroxide/metabolism , Mesenchymal Stem Cell Transplantation/methods , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Acute Kidney Injury/therapy , Culture Media, Conditioned/pharmacology , Cell LineABSTRACT
Background: The objective of this study was to conduct a systematic review and meta-analysis of the clinical application effects of transnasal high flow nasal cannula compared to other conventional modalities for oxygen therapy devices in patients undergoing bronchoscopy. Methods: A comprehensive literature search was conducted in multiple English databases, including PubMed, Web of Science, and Cochrane Library, to collect relevant studies on the application of high flow nasal cannula in patients undergoing bronchoscopy, and conducted a meta-analysis utilizing RevMan 5.4 software, following the predetermined inclusion and exclusion criteria. Results: A total of 12 studies meeting the inclusion criteria were included, involving 1,631 patients (HFNC group: n = 811, other oxygen therapy group: n = 820). The meta-analysis results demonstrated that HFNC significantly reduced the incidence of hypoxemia and improved the minimum oxygen saturation compared to conventional oxygen therapy (RR = 0.27, 95% CI: 0.18-0.41, p < 0.00001; MD = 6.09, 95% CI: 3.73-8.45, p < 0.00001). Furthermore, HFNC showed statistically significant differences when compared to non-invasive ventilation in terms of hypoxemia incidence (RR = 3.52, 95% CI: 1.13-10.97, p = 0.03) and minimum oxygen saturation (MD = -1.97, 95% CI: -2.97--0.98, p < 0.0001). In addition, HFNC resulted in significantly shorter surgical time and higher PaO2 at the end of the procedure compared to conventional oxygen therapy (MD = 1.53, 95% CI: 0.66-2.40, p = 0.0006; MD = 15.52, 95% CI: 10.12-20.92, p < 0.00001). However, there were no statistically significant differences observed in PaCO2, EtCO2, and MAP at the end of the procedure (MD = 1.23, 95% CI: -0.74-3.20, p = 0.22; MD = -0.35, 95% CI: -3.77-3.06, p = 0.84; MD = -0.54, 95% CI: -2.44-1.36, p = 0.58). Conclusion: When HFNC or NIV is utilized during the examination and treatment of bronchoscopy patients, both oxygenation modalities enhance oxygenation function and reduce the incidence of hypoxemia compared to conventional oxygen therapy. HFNC can be regarded as a viable alternative to NIV for specific high-risk patients undergoing bronchoscopy. It decreases the duration of bronchoscopy and improves the PaO2 levels at the end of the procedure, but does not significantly impact the PaCO2, EtCO2, and mean arterial pressure. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier 1414374462@qq.com.
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Network Meta-analysis and multi-criteria decision analysis(MCDA) model were performed to evaluate the benefit-risk of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules in the adjuvant treatment of primary liver cancer(PLC). The randomized controlled trial(RCT) of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules in treating PLC were retrieved from CNKI, Wanfang, VIP, Web of Science, PubMed, and Cochrane Library. R 4.2 was employed to conduct a network Meta-analysis, on the basis of which the effect values of the three medicines were obtained by indirect comparison. MCDA was performed to establish the value tree based on the benefit-risk indexes. Hiview 3.2 was used to calculate the benefit values, risk values, and benefit-risk values of the three medicines in treating PLC, and a sensitivity analysis was carried out to evaluate the robustness of the results. Oracle Crystal Ball 11.1 was employed to optimize the evaluation results by Monte Carlo simulation. A total of 39 RCTs were included. The results showed that Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules combined with transcatheter arterial chemoembolization(TACE) had the benefit values of 45, 51 and 45, the risk values of 59, 47, and 41, and the benefit-risk values of 52, 49, and 43, respectively. The benefit-risk differences and [95%CI] of Compound Cantharis Capsules vs Huisheng Oral Solution, Compound Cantharis Capsules vs Jinlong Capsules, and Huisheng Oral Solution vs Jinlong Capsules were 3.00[-13.09, 21.82], 9.00[-4.39, 24.62], and 6.00[-8.84, 20.28], respectively. Based on the results of MCDA, Huisheng Oral Solution, Jinlong Capsules, and Compound Cantharis Capsules combined with TACE had the greatest benefit, the greatest risk, and the best overall benefit, respectively. Considering the efficacy and safety, the priority of the three oral Chinese patent medicines combined with TACE for treating PLC followed the trend of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules.
Subject(s)
Drugs, Chinese Herbal , Liver Neoplasms , Humans , Drugs, Chinese Herbal/administration & dosage , Liver Neoplasms/drug therapy , Risk Assessment , Network Meta-Analysis , Administration, Oral , Decision Support Techniques , Randomized Controlled Trials as Topic , Nonprescription DrugsABSTRACT
Seven polyketides, including an undescribed depsidone (1) and six previously reported 3,6,8-trihydroxy-1-methylxanthone (2), 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (3), methyl3-chloro-6-hydroxy-2-(4-hy-droxy-2-methoxy-6-methylphenoxy)-4- methoxybenzoate (4), xylarianin A (5), 4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-hydro-xymethyl-2-cyclohexen-1-one (6) and alternariol (7), have been isolated from cultures of the mangrove-derived fungus Penicillium robsamsonii HNNU0006. The structure of compound 1 was elucidated by extensive spectroscopic analysis and X-ray crystallography. Furthermore, all the compounds were evaluated their cytotoxic activities, and compounds 1 and 7 showed weak cytotoxicity against two cell lines Vero and A549 with IC50 values ranging from 95.6 and 296.5 µM, relative to the positive control Etoposide phosphate with IC50 values of 24.5 and 18.7 µM, respectively.
ABSTRACT
Diabetic nephropathy (DN) has emerged as the foremost cause of end-stage renal disease (ESRD) globally. Endoplasmic reticulum (ER) stress plays a critical role in DN progression. Triterpenoid saponin from Aralia taibaiensis (sAT) has been reported to possess anti-diabetic and anti-oxidant effects. The aim of this study was to examine the inï¬uence of sAT on DN treatment and elucidate potential underlying mechanisms. A high-fat diet (HFD) and Streptozotocin (STZ) were employed to induce DN in male Sprague Dawley (SD) rats which were subsequently treated with varying concentrations of sAT for 8 weeks. Our findings reveal that different doses of sAT significantly mitigated hyperglycemia, reduced urinary albumin excretion, and decreased plasma creatinine and blood urea nitrogen levels in DN rats. Moreover, sAT administration improved body weight, alleviated renal fibrosis and histopathological changes in the diabetic kidneys. Notably, sAT treatment partially restored increased Bax expression and decreased Bcl-2 expression. Additionally, sAT inhibited ER stress-related proteins, including GRP78, p-PERK, ATF4 and CHOP in kidneys of DN rats. These results suggest that sAT ameliorated experimental diabetic nephropathy, at least in part, through ER stress pathway. These findings provide a scientiï¬c basis for the potential development of sAT as a therapeutic agent for DN treatment.