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Background: Sepsis-induced acute liver injury (ALI) is a major contributor to mortality in septic patients. Exploring the pathogenesis and developing effective treatment strategies for sepsis-induced ALI is critical for improving patient outcomes. Dachengqi decoction (DCQD), which is a classic Chinese herbal medicine, has been shown to possess potent anti-inflammatory properties. However, the protective effects and underlying mechanisms of DCQD against sepsis-induced ALI remain unclear. This study aimed to investigate the protective effect of DCQD on sepsis-induced ALI and elucidate the involvement of the TGF-1ß/Smad3 pathways. Methods: A septic mouse model was established using caecal ligation and puncture (CLP) to evaluate the protective effect of DCQD on sepsis-induced ALI in vivo. An in vitro cellular inflammation model was established using LPS-stimulated LO2 cells to further investigate the underlying mechanism. Results: DCQD (2.5, 5.0, and 10.0 g/kg body weight) was administered twice daily for 2 days and exerted a dose-dependent protective effect against sepsis-induced ALI. DCQD treatment significantly inhibited inappropriate inflammatory responses and oxidative stress in liver tissue. Moreover, DCQD maintained liver homeostasis by inhibiting hepatocyte apoptosis and improving sepsis-induced liver damage. In vivo and in vitro studies indicated that the TGF-ß1/Smad3 signalling pathway played an important role in sepsis-induced ALI, and DCQD treatment significantly inhibited the activation of this pathway. Conclusions: DCQD can effectively suppress excessive inflammatory responses and oxidative stress, leading to a substantial reduction in hepatocyte apoptosis in sepsis-induced ALI.
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To study the intersystem crossing (ISC) and the spatial confinement of the triplet excited states of organic chromophores, we prepared a series of Bodipy dimers. We found that the connection position of the two units has a significant effect on the absorption and fluorescence. Singlet oxygen quantum yields of 3.8-12.4% were observed for the dimers, which are independent of solvent polarity. Nanosecond transient absorption spectra indicate the population of long-lived triplet excited states with lifetimes (τT) of 45-454 µs. Pulsed laser-excited time-resolved electron paramagnetic resonance (TREPR) spectra show that the T1 triplet states are essentially delocalized, which is different from the case for the previously reported Bodipy dimers. The TREPR spectra of the triplet states imply that the delocalization over the whole dimer essentially depends on the electron density of the carbon atoms at the connection sites. This property may become a universal rule for controlling the T1 state confinement in multichromophore organic molecules.
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Necroptosis is one of the modes of cell death, and its occurrence and development are associated with the development of numerous diseases. To prevent the progression of necroptosis, it is crucial to inhibit the phosphorylation of three proteins: receptor-interacting protein kinase 1 (RIP1), RIP3, and mixed lineage kinase domain-like protein (MLKL). Through virtual and experimental screening approaches, we have identified 8 small molecular inhibitors with potent antinecroptotic activity and binding affinity to RIP1. Among these compounds, SY-1 demonstrated the most remarkable antinecroptotic activity (EC50 = 105.6 ± 9.6 nM) and binding affinity (RIP1 Kd = 49 nM). It effectively blocked necroptosis and impeded the formation of necrosomes by inhibiting the phosphorylations of the RIP1/RIP3/MLKL pathway triggered by TSZ (TNFα, Smac mimetic and Z-VAD-fmk). Furthermore, SY-1 exhibited a protective effect against tumor necrosis factor (TNF)-induced hypothermia in mice and significantly improved the survival rate (100 %, 30 mg/kg) of mice with systemic inflammatory response syndrome (SIRS) in a dose-dependent manner. Pharmacokinetic parameters of SY-1 were also collected in vitro and in vivo. These results strongly suggest that SY-1 and its derivatives warrant further investigation for their potential therapeutic applications.
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Necroptose , Proteínas Quinases , Animais , Camundongos , Proteínas Quinases/metabolismo , Necroptose/fisiologia , Morte Celular , Fosforilação , Fatores de Transcrição/metabolismo , ApoptoseRESUMO
Background: With the establishment of the cardiac-gut axis concept, increasing evidence has suggested the involvement and important regulatory role of the gut microbiota (GM) and short chain fatty acid (SCFA) in cardiovascular diseases. However, the relationship between GM and atrial fibrillation (AF) is still poorly understood. Objectives: The aim of this study was to investigate whether there were differences in GM and SCFA between AF patients and healthy controls. Methods: In this study, we enrolled 30 hospitalized patients with AF and 30 matched patients with sinus rhythm (SR). GM species in fecal samples were evaluated through amplicon sequencing targeting the 16Sribosomal RNA gene. The feces SCFAs were describe step by step the quantitative analysis using gas chromatography-mass spectrometry (GC-MS). GM species richness, diversity, differential abundance of individual taxa between AF and SR were analyzed. Results: AF patients showed decreased species richness and α-diversity compared to SR patients, but there was no statistical difference. The phylogenetic diversity was significant decreased in AF group. The ß-diversity indexes revealed significant differences in GM community structure between the AF group and the SR group. After investigated the individual taxa, AF group showed altered relative abundance in several taxa compared to the SR group. linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed, a significant decrease in Bifidobacterium and a greater abundance of Lactobacillus, Fusobacterium, Haemophilus in AF group compared with the SR group. The abundance of haemophilus was negative correlated with isovaleric acid and isobutyric acid. Conclusions: In AF patients, the GM phylogenetic diversity and ß-diversity decreased, the relative abundance altered in several taxa and the bacterial community structure changed as well as the SCFA level. GM and SCFA dysbiosis might play a crucial part in the occurrence and development of AF.
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Fibrilação Atrial , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , Filogenia , Ácidos Graxos Voláteis/análise , Fezes/químicaRESUMO
Chemoprevention is a potential strategy to reduce lung cancer incidence and death. Recently, we reported that garlic oil significantly inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis. Diallyl disulfide (DADS) is a bioactive ingredient in garlic. Our goal was to examine the chemopreventive effectiveness and mechanism of DADS on NNK-triggered lung cancer in vivo and in vitro in the current investigation. The results indicated that DADS significantly reduced the number of lung nodules in the NNK-induced A/J mice. Consistent with the in vivo results, DADS markedly inhibited NNK-induced decrease of MRC-5 cells' viability. Mechanistically, DADS could promote Nrf2 dissociated from the Keap1-Nrf2 complex and accelerate Nrf2 nuclear translocation, which in turn upregulates its downstream target genes. Besides, DADS further inhibited the NF-κB signaling cascade, thus reducing the accumulation of inflammatory factors. Collectively, these discoveries supported the potential of DADS as a novel candidate for the chemoprevention of tobacco-carcinogen-induced lung cancer.
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Neoplasias Pulmonares , Nitrosaminas , Produtos do Tabaco , Camundongos , Animais , Carcinógenos/toxicidade , NF-kappa B/genética , NF-kappa B/metabolismo , Antioxidantes/efeitos adversos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch , Nitrosaminas/toxicidade , Pulmão/metabolismo , Carcinogênese , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/prevenção & controleRESUMO
Optical microcavities have the ability to confine photons in small mode volumes for long periods of time, greatly enhancing light-matter interactions, and have become one of the research hotspots in international academia. In recent years, sensing applications in complex environments have inspired the development of multimode optical microcavity sensors. These multimode sensors can be used not only for multi-parameter detection but also to improve measurement precision. In this review, we introduce multimode sensing methods based on optical microcavities and present an overview of the multimode single/multi-parameter optical microcavities sensors. Expected further research activities are also put forward.
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We prepared a rhodamine-TEMPO chromophore-radical dyad (RB-TEMPO) to study the radical enhanced intersystem crossing (REISC). The visible light-harvesting chromophore rhodamine is connected with the TEMPO (a nitroxide radical) via a C-N bond. The UV-vis absorption spectrum indicates negligible electron interaction between the two units at the ground state. Interestingly, the fluorescence of the rhodamine moiety is strongly quenched in RB-TEMPO, and the fluorescence lifetime of the rhodamine moiety is shortened to 0.29 ns, from the lifetime of 3.17 ns. We attribute this quenching effect to the intramolecular electron spin-spin interaction between the nitroxide radical and the photoexcited rhodamine chromophore. Nanosecond transient absorption spectra confirm the REISC in RB-TEMPO, indicated by the detection of the rhodamine chromophore triplet excited state; the lifetime was determined as 128 ns, which is shorter than the native rhodamine triplet state lifetime (0.58 µs). The zero-field splitting (ZFS) parameters of the triplet state of the chromophore were determined with the pulsed laser excited time-resolved electron paramagnetic resonance (TREPR) spectra. RB-TEMPO was used as a photoinitiator for the photopolymerization of pentaerythritol triacrylate (PETA). These studies are useful for the design of heavy atom-free triplet photosensitizers, the study of the ISC, and the electron spin dynamics of the radical-chromophore systems upon photoexcitation.
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Luz , Xantenos , Espectroscopia de Ressonância de Spin Eletrônica , RodaminasRESUMO
Receptor-interacting protein kinase 1 (RIPK1)-mediated necroptosis is believed to have a significant role in contributing to inflammatory diseases. Inhibiting RIPK1 has shown promise in effectively alleviating the inflammation process. In our current study, we employed scaffold hopping to develop a series of novel benzoxazepinone derivatives. Among these derivatives, compound o1 displayed the most potent antinecroptosis activity (EC50=16.17±1.878nM) in cellular assays and exhibited the strongest binding affinity to the target site. Molecular docking analyses further elucidated the mechanism of action of o1, revealing its ability to fully occupy the protein pocket and form hydrogen bonds with the amino acid residue Asp156. Our findings highlight that o1 specifically inhibits necroptosis, rather than apoptosis, by impeding the RIPK1/Receptor-interacting protein kinase 3 (RIPK3)/mixed-lineage kinase domain-like (MLKL) pathway's phosphorylation, triggered by TNFα, Smac mimetic, and z-VAD (TSZ). Additionally, o1 demonstrated dose-dependent improvements in the survival rate of mice with Systemic Inflammatory Response Syndrome (SIRS), surpassing the protective effect observed with GSK'772.
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Necroptose , Inibidores de Proteínas Quinases , Proteína Serina-Treonina Quinases de Interação com Receptores , Animais , Camundongos , Apoptose , Simulação de Acoplamento Molecular , Fosforilação , Proteínas Quinases/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/antagonistas & inibidores , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Necroptose/efeitos dos fármacos , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologiaRESUMO
We propose a dual-parameter sensor for the simultaneous detection of temperature and pressure based on a single packaged microbubble resonator (PMBR). The ultrahigh-quality (â¼107) PMBR sensor exhibits long-term stability with the maximum wavelength shift about 0.2056 pm. Here, two resonant modes with different sensing performance are selected to implement the parallel detection of temperature and pressure. The temperature and pressure sensitivities of resonant Mode-1 are -10.59 pm/°C and 0.1059 pm/kPa, while the sensitivities of Mode-2 are -7.69 pm/°C and 0.1250 pm/kPa, respectively. By adopting a sensing matrix, the two parameters are precisely decoupled and the root mean square error of measurement are â¼ 0.12 °C and â¼ 6.48 kPa, respectively. This work promises the potential for the multi-parameters sensing in a single optical device.
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Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Α function. The results showed that the HIF1Α and enolase 2 (ENO2) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically, HIF1Α directly binds to the DNA promoter region and upregulates the transcription of ENO2; ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.
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Neoplasias do Colo , Flavanonas , Glicólise , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neoplasias do Colo/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fosfopiruvato Hidratase/metabolismo , Flavanonas/farmacologia , Linhagem Celular Tumoral , Bases de Dados Genéticas , Proliferação de Células/efeitos dos fármacos , Transfecção , Efeito Warburg em OncologiaRESUMO
Zebra finches are essential animal models for studying learned vocal signals. The robust nucleus of the arcopallium (RA) plays an important role in regulating singing behavior. Our previous study showed that castration inhibited the electrophysiological activity of RA projection neurons (PNs) in male zebra finches, demonstrating that testosterone modulates the excitability of RA PNs. Testosterone can be converted into estradiol (E2) in the brain through aromatase; however, the physiological functions of E2 in RA are still unknown. This study aimed to investigate the electrophysiological activities of E2 on the RA PNs of male zebra finches through patch-clamp recording. E2 rapidly decreased the rate of evoked and spontaneous action potentials (APs) of RA PNs, hyperpolarized the resting membrane potential, and decreased the membrane input resistance. Moreover, the G-protein-coupled membrane-bound estrogen receptor (GPER) agonist G1 decreased both the evoked and spontaneous APs of RA PNs. Furthermore, the GPER antagonist G15 had no effect on the evoked and spontaneous APs of RA PNs; E2 and G15 together also had no effect on the evoked and spontaneous APs of RA PNs. These findings suggested that E2 rapidly decreased the excitability of RA PNs and its binding to GPER suppressed the excitability of RA PNs. These pieces of evidence helped us fully understand the principle of E2 signal mediation via its receptors to modulate the excitability of RA PNs in songbirds.
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Acquired long QT syndrome caused by hypopituitarism and transient ST-segment elevation has not been reported in cardiac arrest patients. We report a case of extremely dangerous acquired long QT syndrome and transient ST-segment elevation. A 44-year-old Chinese woman with renal failure experienced sudden cardiac arrest in the haemodialysis room. Subsequent electrocardiogram showed QT prolongation and transient ST-segment elevation. This patient's medical history, subsequent laboratory results and pituitary magnetic resonance imaging suggested hypopituitarism. Transient ST-segment elevation on the electrocardiogram was considered to be caused by repeated direct current shocks. The patient was diagnosed with acquired long QT syndrome and was not taking any antiarrhythmic drugs. Her corrected QT interval normalized after hormone replacement therapy. This case highlights the importance of the awareness of hypopituitarism; early identification and intervention can prevent the occurrence of this life-threatening arrhythmia. ST-segment elevation is not always due to acute myocardial infarction, and a variety of other causes, especially electrical cardioversion, should be considered.
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Cannabinoid receptors belong to the large family of G-protein-coupled receptors, which can be divided into two receptor types, cannabinoid receptor type-1 (CB1) and cannabinoid receptor type-2 (CB2). Marinol, Cesamet and Sativex are marketed CB1 drugs which are still in use and work well, but the central nervous system side effects caused by activation CB1, which limited the development of CB1 ligands. So far, no selective CB2 ligand has been approved for marketing, but lots of its ligands in the clinical stage and pre-clinical stage have positive effects on the treatment of some disease models and have great potential for development. Most selective CB2 agonists are designed and synthesized based on non-selective CB2 agonists through the classical med-chem strategies, e.g. molecular hybridization, scaffold hopping, bioisosterism, etc. During these processes, the balance between selectivity, activity, and pharmacokinetic properties needs to be achieved. Hence, we summarized some reported ligands on the basis of the optimization strategies in recent 10 years, and the limitations and future directions.
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Appropriate inflammation is an effective weapon for the body to fight against harmful stimuli, while excessive or prolonged inflammatory reactions could lead to tissue destruction, fibrosis, and even organ failure. The timely termination of inflammatory response is of great significance for maintaining the homeostasis of the body. Unlike the past perception that the regression of inflammation is a passive process, it is now considered that the regression of inflammation is a carefully coordinated active process. Specialized pro-resolving mediators (SPMs) play an important role in limiting the inflammatory response, promoting the regression of inflammation, and maintaining homeostasis. Increasing evidence suggests that exogenous treatment with SPMs could effectively improve symptoms in various inflammatory-related diseases. In this review, we briefly address the current family members of SPMs. We elaborated on the extensive regulation of SPMs of multiple immune cells in various inflammatory-related diseases and the related mechanisms. Our research provides a theoretical basis for promoting an understanding of the role and mechanism of SMPs in inflammation.
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Mediadores da Inflamação , Inflamação , Humanos , Inflamação/tratamento farmacológico , Fibrose , HomeostaseRESUMO
Colonic metastases of lung adenocarcinoma are extremely rare. Signet ring cell adenocarcinoma (SRCA) has not been described in patients with gastrointestinal metastasis of lung adenocarcinoma. SRCA is a unique subtype of adenocarcinoma with strong invasion and a poor prognosis, and most SRCA found in the lung are due to gastrointestinal metastases. This report describes a rare case of colonic metastasis from primary lung SRCA. A 64-year-old female was admitted to Sun Yat-sen University Cancer Center for feeling of nausea and malaise. Following a positron emission tomography CT (PET-CT) scan, widespread metastases of tumor cells were found in the bilateral lung, liver, bone, and multiple lymph nodes, but there was no evidence of metastasis to the colon. Two months later, the patient received a liver biopsy at Tongji Hospital in Wuhan. Pathology revealed a poorly differentiated adenocarcinoma with SRCA conformation, but immunohistochemical staining did not identify the original source of tumor cells. Considering that SRCA mainly derives from the gastrointestinal tract and that serum gastrointestinal tumor markers were elevated, we performed gastrointestinal endoscopy on the patient. The results showed an isolated polyp in the colon, and the pathology results indicated a poorly differentiated adenocarcinoma that was considered to originate from the lung based on immunohistochemical staining. Meanwhile, genetic tests identified a BRAF V600E mutation. The final diagnosis was colonic metastasis of BRAFV 600E mutated lung SRCA. Considering the positive expression of EGFR in this case, cetuximab was innovatively added to the first-line treatment regime (dabrafenib and trametinib). To date, the patient has received thirty-two weeks of treatment. Interestingly, lung and liver tumors shrank and tumor markers in the blood normalized. Our findings offer valuable diagnostic and therapeutic information for colonic metastasis of BRAFV600E mutant primary lung adenocarcinoma with signet ring cell features.
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PURPOSE: Osteoarthritis (OA) is a common disease for human beings, characterized by severe inflammation, cartilage degradation, and subchondral bone destruction. However, current therapies are limited to relieving pain or joint replacement and no effective treatment methods have been discovered to improve degenerative changes. Currently, a variety of evidences have indicated that aberrant mechanical stimuli is closely associated with articular joint pathogenesis, while the detailed underlying mechanism remains unelucidated. In the present study, we determined to investigate the impact of excessive high fluid shear stress (FSS) on primary chondrocytes and the underlying epigenetic mechanisms. MATERIALS AND METHODS: Phalloidin staining and EdU staining were used to evaluate cell morphology and viability. The mRNA level and protein level of genes were determined by qPCR, Western blot assay, and immunofluorescence staining. Mechanistic investigation was performed through RNA-sequencing and CUT&Tag sequencing. In vivo, we adopted unilateral anterior crossbites (UAC) mice model to investigate the expression of H3K4me3 and ZBTB20 in aberrant force-related cartilage pathogenesis. RESULTS: The results demonstrated that FSS greatly disrupts cell morphology and significantly decreased chondrocyte viability. Aberrant FSS induces remarkable inflammatory mediators production, leading to cartilage degeneration and degradation. In depth mechanistic study showed that FSS results in more than 10-fold upregulation of H3K4me3, and the modulatory effect of H3K4me3 on cartilage was obtained by directly targeting ZBTB20. Furthermore, Wnt signaling was strongly activated in high FSS-induced OA pathogenesis, and the negative impact of ZBTB20 on chondrocytes was also achieved through activating Wnt signaling pathway. Moreover, pharmacological inhibition of H3K4me3 activation by MM-102 or treatment with Wnt pathway inhibitor LF3 could effectively alleviate the destructive effect of FSS on chondrocytes. In vivo UAC mice model validated the dysregulation of H3K4me3 and ZBTB20 in aberrant force-induced cartilage pathogenesis. CONCLUSION: Through the combination of in vitro FSS model and in vivo UAC model, KMT2B-H3K4me3-ZBTB20 axis was first identified in aberrant FSS-induced cartilage pathogenesis, which may provide evidences for epigenetic-based therapy in the future.
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Developmental defects of primitive choanae, an anatomical path to connect the embryonic nasal and oral cavity, result in disorders called choanal atresia (CA), which are associated with many congenital diseases and require immediate clinical intervention after birth. Previous studies revealed that reduced retinoid signaling underlies the etiology of CA. In the present study, by using multiple mouse models which conditionally deleted Rdh10 and Gata3 during embryogenesis, we showed that Gata3 expression is regulated by retinoid signaling during embryonic craniofacial development and plays crucial roles for development of the primitive choanae. Interestingly, Gata3 loss of function is known to cause hypoparathyroidism, sensorineural deafness and renal disease (HDR) syndrome, which exhibits CA as one of the phenotypes in humans. Our model partially phenocopies HDR syndrome with CA, and is thus a useful tool for investigating the molecular and cellular mechanisms of HDR syndrome. We further uncovered critical synergy of Gata3 and retinoid signaling during embryonic development, which will shed light on novel molecular and cellular etiology of congenital defects in primitive choanae formation.
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Perda Auditiva Neurossensorial , Hipoparatireoidismo , Nefrose , Animais , Fator de Transcrição GATA3/genética , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Neurossensorial/genética , Hipoparatireoidismo/genética , Camundongos , Nasofaringe , Nefrose/complicações , Nefrose/genética , TretinoínaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Lianhuaqingwen (LHQW) is a Chinese medicine, developed from appropriate addition and reduction of combined traditional Chinese medicine (TCM) Yinqiao San and Maxing Shigan decoction. LHQW has been used in routine influenza treatment for decades and plays a role in a broad-spectrum therapy on various influenza viruses. AIMS OF THE STUDY: The therapeutic effects of LHQW in coronavirus disease 2019 (COVID-19) have not been fully elucidated. A retrospective study was conducted in patients with COVID-19 to evaluate the influence of LHQW on laboratory results related to the disease, and to provide evidence for the clinical practice of TCM. MATERIALS AND METHODS: We retrospectively collected 248 patients who met the moderate type COVID-19 diagnostic criteria, and received treatment in Tongji Hospital. Patients were divided into control (158 cases, standard treatment) and LHQW treatment (90 cases, standard treatment combined with LHQW) groups according to the different treatments administered. All laboratory data were obtained after 5-7 days' treatment. RESULTS: In this study, the average patient age was 58.95 years and 131 patients were male. The two groups were comparable in demographic characteristics, symptoms, and treatment. Compared with in the control group, D-dimer and erythrocyte sedimentation rate were significantly lower in the LHQW treatment group (2.47 ± 4.67 vs. 1.68 ± 3.61; 44.47 ± 30.24 vs. 35.39 ± 27.43; both P < 0.05). Lymphocyte counts, albumin and hemoglobin levels were higher in the LHQW treatment group than those in the control group (1.00 ± 0.46 vs. 1.13 ± 0.5; 34.39 ± 5.2 vs. 35.71 ± 4.76; 127.03 ± 16.58 vs. 131.11 ± 14.66; both P < 0.05). CONCLUSION: The study showed that LHQW significantly improved laboratory results of patients with COVID-19 and could be effectively applied alongside standard treatment of patients with moderate type COVID-19, providing preliminary clinical research evidence for the use of TCM in treatment of this disease.
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Tratamento Farmacológico da COVID-19 , Medicamentos de Ervas Chinesas/uso terapêutico , SARS-CoV-2 , Adulto , Idoso , Citocinas/genética , Citocinas/metabolismo , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
A DNA-encoded library is a collection of small molecules covalently linked to DNA that has unique information about the identity and the structure of each library member. A DNA-encoded chemical library (DEL) is broadly adopted by major pharmaceutical companies and used in numerous drug discovery programs. The application of the DEL technology is advantageous at the initial period of drug discovery because of reduced cost, time, and storage space for the identification of target compounds. The key points for the construction of DELs comprise the development and the selection of the encoding methods, transfer of routine chemical reaction from off-DNA to on-DNA, and exploration of new chemical reactions on DNA. The limitations in the chemical space and the diversity of DEL were reduced gradually by using novel DNA-compatible reactions based on the formation and the cleavage of various bonds. Here, we summarized a series of novel DNA-compatible chemistry reactions for DEL building blocks and analysed the druggability of screened hit molecules via DELs in the past five years.
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BACKGROUND: Esophageal carcinoma is an invasive malignancy with a poor prognosis. Inflammatory cells are related to the prognosis in many malignancies; however, the prognostic values of preoperative neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR) and platelet-lymphocyte ratio (PLR) in esophageal squamous cell carcinomas (ESCCs) are contentious. METHODS: We performed a retrospective study on 178 patients who had proven ESCC and underwent R0 resection. A complete peripheral blood cell count on all patients 1 week before surgery was used to calculate NLR, LMR and PLR. All patients were grouped by the median count of NLR, LMR and PLR respectively. Kaplan-Meier curves were adopted to test the difference of overall survival (OS) and disease-free survival (DFS) between the high group of NLR, LMR and PLR and the low group. All data analysis was performed by SPSS. P<0.05 was assigned to admit statistical significance. RESULTS: The median follow-up after the surgery was 39 months. The preoperative LMR showed no significant association with the OS [hazard ratio (HR) =0.733, 95% confidence interval (CI): 0.397-1.353, P=0.321] and DFS (HR =0.850, 95% CI: 0.491-1.473, P=0.562). Neither NLR nor PLR exhibited a significant correlation with OS or DFS. CONCLUSIONS: NLR, LMR, and PLR could not take the roles of prognostic biomarkers for patients with operable ESCCs.