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1.
J Org Chem ; 89(3): 2039-2049, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38241277

RESUMO

The application of the DMSO/SOCl2 system enabled the intramolecular cyclization/chlorination of N,N-disubstituted 2-alkynylanilines, leading to the synthesis of a series of 3-chloroindoles with moderate to good yields. Differing from the previously reported interrupted Pummerer reaction featuring the introduction of SMe moiety, the current approach adopted an alternative pathway that realized the incorporation of chlorine atom to the indole skeleton via a desulfonylative chlorocyclization process.

2.
Org Biomol Chem ; 22(19): 3882-3886, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38656307

RESUMO

The combining use of BnSCF2D, mCPBA and Tf2O serves as an efficient multi-component reagents system (MCRS) for the synthesis of deuteriodifluoromethylthiolated isocoumarins-1-imines/isocoumarins via intramolecular cyclization/deuteriodifluoromethylthiolation of 2-alkynylbenzamides/2-alkynylbenzoates. The approach features the generation of the crucial reactive electrophilic sulfonium salt through a sequence process involving the oxidation of BnSCF2D by mCPBA followed by Tf2O promoted activation.

3.
Nutr Neurosci ; : 1-17, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622917

RESUMO

OBJECTIVES: The study aimed to explore whether TP could improve memory in the aged type 2 diabetic rat model by regulating microbiota-immune-synaptic plasticity axis. METHODS: The experiment was divided into two parts. Firstly, to investigate the effects of TP on the physiopathology of the aged T2DM model rats, rats were randomly divided into the Normal control group, the aged group, the Aged T2DM model group, the TP 75, 150, 300 mg/kg groups, the 150 mg/kg Piracetam group and the 3 mg/kg Rosiglitazone group. Then, to further verify whether TP improved memory in aged T2DM rat model by regulating intestinal flora, the fecal microbiota transplantation (FMT) from the rats in the 300 mg/kg TP group into the rats in the aged T2DM model group was carried out. Effects on gut microbiota, colonic integrity (epithelial tight junction proteins), and endotoxemia (serum LPS) were examined, along with synaptic structure, synaptic plasticity-related structural proteins and inflammation signaling of the hippocampus in our study. RESULTS: Our results demonstrated that TP alleviated memory impairments in the aged T2DM rat model. The specific outcomes were as follows: TP 300 mg/kg corrected the gut dysbacteriosis, alleviated intestinal permeability reduction and peripheral/central inflammation, inhibited the TLR4/NF-κB signaling pathway. Meanwhile, TP improved the synaptic plasticity in the hippocampus of the aged T2DM model rats, whose expressions of SYN, PSD 95, NMDAR1 and GluR1 in hippocampus were significantly up-regulated. Surprisingly, rats of the FMT group displayed the same changes. DISCUSSION: TP improves the memory in aged T2DM rat model. The mechanism may be related to the alteration of gut flora, which can inhibit hippocampal TLR4/NF-κB signaling to attenuate neuroinflammation, then improve synaptic plasticity. The study proposes that TP interventions aimed at manipulating the gut microbiota may hold great potential as an effective approach for preventing and treating this disease.

4.
Wei Sheng Yan Jiu ; 53(4): 540-546, 2024 Jul.
Artigo em Zh | MEDLINE | ID: mdl-39155220

RESUMO

OBJECTIVE: To explore whether tea polyphenols(TP) improve sarcopenia in the aged type 2 diabetes(T2DM)model rats via mitochondrial quality control(MQC). METHODS: A total of 55 2-month-old male SD rats were randomly divided into the control group(n=10), the aged model group(aged, n=10) and the aging T2DM model group(n=35). The aging T2DM model group rats were fed with high-sugar and high-fat diet and intraperitoneally injected with 50 mg/kg D-galactose daily. After 4 weeks, the aging T2DM model group rats were given a single intraperitoneal injection of 30 mg/kg streptozotocin(STZ). After STZ injection for 2 weeks, fasting blood glucose(FBG) ≥ 16.7 mmol/L was defined as successful T2DM model. When the model was successfully induced, the 30 model rats were randomly divided into aged T2DM group(Mod), 300 mg/kg TP teatment group(TP) and 3 mg/kg rosiglitazone treatment group(RSG) according to FBG, with 10 rats in each group. Each group was treated with 50 mg/kg D-galactose to induce senescence and fed with high glucose and fat for 8 weeks. Western blot was used to detect the expression of P53 protein in gastnemius muscle tissue of the model group at the end of the experiment, which was higher than that of the control group, indicating that the aging T2DM model was successfully established. FBG was detected by the blood glucose meter, gastnemius muscle relative weights was calculated, the microstructure of mitochondria of gastnemius muscle was observed by transmission electron microscope(TEM), the expression of mitochondrial biosynthesis-related proteins PGC-1α, mitochondrial dynamics-related proteins(OPA1, DRP1) and mitochondrial autophagy-related proteins(P62, LC3) in gastnemius muscle were detected by western blot. RESULTS: Compared with the control group, the level of FBG and the expression of P53 in the Mod group were increased(P<0.01). The gastnemius muscle relative weights, the expression level of PGC-1α, OPA1 and the ratio of LC3II/LC3I were decreased(P<0.01). The expression level of P62 and DRP1 were significantly increased(P<0.01). The number of mitochondria decreased, the volume decreased and a large number of vacuolization, and there were no obvious autophagolysosomes and fission and fusion. After 8 weeks, compared with the Mod group, the number of mitochondria in the gastrocnemius of TP and RSG groups, vacuolization, fission and fusion were improved, and the autophagolysosomes was significantly increased. The expression levels of P53, DRP1 and P62, the level of FBG in the TP group were significantly decreased(P<0.01, P<0.05). The expression levels of OPA1 and PGC-1α, the ratios of LC3II/LC3I and gastnemius muscle relative weights were significantly increased(P<0.05, P<0.01). CONCLUSION: TP can improve the sarcopenia in the aged T2DM model rats, and its mechanism is related to the regulation of mitochondrial quality control.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Polifenóis , Ratos Sprague-Dawley , Sarcopenia , Chá , Animais , Masculino , Polifenóis/farmacologia , Ratos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Chá/química , Sarcopenia/prevenção & controle , Sarcopenia/metabolismo , Sarcopenia/tratamento farmacológico , Sarcopenia/etiologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Envelhecimento , Modelos Animais de Doenças , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos
5.
Wei Sheng Yan Jiu ; 53(1): 71-87, 2024 Jan.
Artigo em Zh | MEDLINE | ID: mdl-38443175

RESUMO

OBJECTIVE: To investigate the effect of tea polyphenols(TP) on improving depression-like behavior in aged type 2 diabetes(T2DM) model rats. METHODS: A total of 40 8-week-old SD male rats were randomly divided into the control group(n=10) and the modeling group(n=30) according to the body weight. The rats in the modeling group were fed with high-glucose and high-fat diet and treated with 50 mg/kg D-galactose by intraperitoneal injection daily until the end of the experiment, while the rats in the control group were fed with the standard diet and treated with an equal volume of saline by intraperitoneal injection. After 4 weeks, the rats in the modeling group were injected with 25 mg/kg STZ, meanwhile the rats in the control group were injected with an equal volume of citric acid buffer. The level of fasting blood glucose(FBG) was measured on the 14~(th) day. When FBG≥16.7 mmol/L, the rats were identified as successful model of the T2DM rats. Then, the model rats were randomly divided into the model group, 150, 300 mg/kg TP groups(n=10, respectively), and the rats were given intragastric intervention for 8 weeks. The levels of the FBG were detected, and the depression-like behavior of rats was assessed by the open field test(OFT) and forced swimming test(FST). The density of microglia in hippocampus CA1 region was assessed by immunofluorescence staining, and protein expressions of P53, Iba1, iNOS, Arg-1 and BDNF were determined by western blot. RESULTS: Compared with the control group, the levels of FBG in the rats of the model group were obviously increased(P<0.01). In the OFT, the frequencies of rearing and grooming in the rats of model group markedly was decreased, while in the FST, the immobility time extensively was increased(P<0.01). The density of microglia in hippocampus CA1 region was increased(P<0.01). The expressions of P53, Iba1 and iNOS were increased, and the expressions of Arg-1 and BDNF were decreased(P<0.01). Additionally, compared with the model group, in the OFT, the frequencies of rearing and grooming were increased in the rats in 150 and 300 mg/kg TP group(P<0.01). The density of microglia in hippocampus CA1 region was decreased(P<0.01). The expressions of P53, Iba1 and iNOS were down-regulated, and the expression of BDNF was up-regulated(P<0.01). Additionally, compared with the model group, the levels of FBG was decreased in the rats in the 300 mg/kg TP group(P<0.01). The immobility time was decreased in the FST(P<0.01). The expression of Arg-1 was down-regulated(P<0.01). CONCLUSION: TP can improve depression-like behavior in aged T2DM model rats, and its mechanism may be related to regulate microglia M1/M2 polarization and up-regulate expression of BDNF in hippocampus.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Diabetes Mellitus Tipo 2 , Masculino , Animais , Ratos , Depressão/tratamento farmacológico , Microglia , Proteína Supressora de Tumor p53 , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Chá
6.
Beilstein J Org Chem ; 20: 1453-1461, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952956

RESUMO

A series of 4-thio/seleno-cyanated pyrazoles was conveniently synthesized from 4-unsubstituted pyrazoles using NH4SCN/KSeCN as thio/selenocyanogen sources and PhICl2 as the hypervalent iodine oxidant. This metal-free approach was postulated to involve the in situ generation of reactive thio/selenocyanogen chloride (Cl-SCN/SeCN) from the reaction of PhICl2 and NH4SCN/KSeCN, followed by an electrophilic thio/selenocyanation of the pyrazole skeleton.

7.
J Biol Chem ; 298(8): 102149, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35787372

RESUMO

Skeletal muscle differentiation (myogenesis) is a complex and highly coordinated biological process regulated by a series of myogenic marker genes. Chromatin interactions between gene's promoters and their enhancers have an important role in transcriptional control. However, the high-resolution chromatin interactions of myogenic genes and their functional enhancers during myogenesis remain largely unclear. Here, we used circularized chromosome conformation capture coupled with next generation sequencing (4C-seq) to investigate eight myogenic marker genes in C2C12 myoblasts (C2C12-MBs) and C2C12 myotubes (C2C12-MTs). We revealed dynamic chromatin interactions of these marker genes during differentiation and identified 163 and 314 significant interaction sites (SISs) in C2C12-MBs and C2C12-MTs, respectively. The interacting genes of SISs in C2C12-MTs were mainly involved in muscle development, and histone modifications of the SISs changed during differentiation. Through functional genomic screening, we also identified 25 and 41 putative active enhancers in C2C12-MBs and C2C12-MTs, respectively. Using luciferase reporter assays for putative enhancers of Myog and Myh3, we identified eight activating enhancers. Furthermore, dCas9-KRAB epigenome editing and RNA-Seq revealed a role for Myog enhancers in the regulation of Myog expression and myogenic differentiation in the native genomic context. Taken together, this study lays the groundwork for understanding 3D chromatin interaction changes of myogenic genes during myogenesis and provides insights that contribute to our understanding of the role of enhancers in regulating myogenesis.


Assuntos
Diferenciação Celular , Cromatina , Elementos Facilitadores Genéticos , Desenvolvimento Muscular , Mioblastos , Animais , Linhagem Celular , Cromatina/genética , Cromatina/metabolismo , Código das Histonas , Camundongos , Desenvolvimento Muscular/genética , Fibras Musculares Esqueléticas , Mioblastos/citologia
8.
Ann Surg ; 278(5): e988-e994, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37309899

RESUMO

OBJECTIVES: We aimed to determine the current incidence rate and risk factors for surgical site infection (SSI) after abdominal surgery in China and to further demonstrate the clinical features of patients with SSI. BACKGROUND: Contemporary epidemiology and clinical features of SSI after abdominal surgery remain poorly characterized. METHODS: A prospective multicenter cohort study was conducted from March 2021 to February 2022; the study included patients who underwent abdominal surgery at 42 hospitals in China. Multivariable logistic regression analysis was performed to identify risk factors for SSI. Latent class analysis (LCA) was used to explore the population characteristics of SSI. RESULTS: In total, 23,982 patients were included in the study, of whom 1.8% developed SSI. There was a higher SSI incidence in open surgery (5.0%) than in laparoscopic or robotic surgeries (0.9%). Multivariable logistic regression indicated that the independent risk factors for SSI after abdominal surgery were older age, chronic liver disease, mechanical bowel preparation, oral antibiotic bowel preparation, colon or pancreas surgery, contaminated or dirty wounds, open surgery, and colostomy/ileostomy. LCA revealed 4 subphenotypes in patients undergoing abdominal surgery. Types α and ß were mild subclasses with a lower SSI incidence; whereas types γ and δ were the critical subgroups with a higher SSI incidence, but their clinical features were different. CONCLUSIONS: LCA identified 4 subphenotypes in patients who underwent abdominal surgery. Types γ and δ were critical subgroups with a higher SSI incidence. This phenotype classification can be used to predict SSI after abdominal surgery.


Assuntos
Laparoscopia , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Estudos Prospectivos , Estudos de Coortes , Laparoscopia/efeitos adversos , Fatores de Risco , Incidência
9.
BMC Ophthalmol ; 23(1): 241, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37254066

RESUMO

BACKGROUND: The coexistence of MRCS (microcornea, retinal dystrophy, cataract, and posterior staphyloma) syndrome and extremely long axis is rare since microcornea frequently accompanies with diminution of entire anterior segment and occasionally the whole globe. In the case presented here, combination of these two elements were identified, together with XFS (exfoliation syndrome). CASE PRESENTATION: A 66-year-old Han Chinese woman presented for consultation due to impaired vision which accompanied throughout her entire life span and worsened during the last 2 years. Combination of MRCS syndrome and extremely long axial length was evidently diagnosed in both eyes, with XFS confirmed in her right eye, but mutation screening failed to identify disease-causing sequence variants in some specific genes reported previously, including BEST1 and ARL2. However, likely pathogenic mutations in FBN2 gene were identified. Bilateral cataract phacoemulsification without intraocular lens implantation was performed using scleral tunnel incision and under general anesthesia. At 3-month follow-up, ocular recovery of the patient was satisfactory. CONCLUSIONS: The case presented here exhibited rare coexistence of MRCS syndrome, extremely long axis and XFS. The complexity of her ocular abnormalities brought challenges to surgical management, in which multidisciplinary collaboration is often required. Furthermore, the genetic analysis in this case yielded a possible novel candidate gene for MRCS syndrome and provided evidence in support of genetic heterogeneity in this phenotype.


Assuntos
Extração de Catarata , Catarata , Síndrome de Exfoliação , Facoemulsificação , Distrofias Retinianas , Feminino , Humanos , Síndrome de Exfoliação/complicações , Síndrome de Exfoliação/diagnóstico , Síndrome de Exfoliação/genética , Catarata/complicações , Catarata/diagnóstico , Catarata/genética , Proteínas de Ligação ao GTP , Bestrofinas
10.
BMC Ophthalmol ; 23(1): 467, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978355

RESUMO

BACKGROUND: To explore the predictive value of Ellipsoid Zone (EZ) -related angle parameters for the outcome of primary macular hole surgery. METHODS: This was a retrospective study. Patients diagnosed with large macular hole (MH) (minimum diameter > 500 µm) between 2018 and 2021 were enrolled. All patients underwent 25-gauge pars plana vitrectomy, internal limiting membrane (ILM) peeling and air tamponade. Spectral-domain OCT (SD-OCT) and best corrected visual acuity (BCVA) were measured in preoperative and 2-week post-operative. Classic and angle related parameters were measured via ImageJ. Angle regularity (AR) were defined as the standard deviation of the angle parameters in vertical and horizontal direction. RESULTS: Seventy-six eyes were included for analysis; 24 eyes showed an unclosed macular hole at the 2-week postoperative and 52 eyes showed a closed hole. Preoperatively, MLD (P < 0.001), BD (P = 0.009) and diameter of EZ/ELM disruption (P = 0.002 and 0.025) in patients failed to close the hole after primary surgery were significantly larger than those succeeded. EZ-MH (P = 0.018), EZ-NFL (P = 0.006), EZ-GCL (P = 0.004), EZ-INL (P = 0.002), EZ-OPL (P = 0.009) and EZ-ONL (P = 0.011) angles were smaller in patients with unclosed hole. AR of the EZ-NFL (P = 0.009), EZ-GCL (P = 0.009), EZ-OPL (P = 0.023), EZ-ONL (P = 0.048) and Basal-NFL (P = 0.030) angles among the unclosed patients were significantly larger than those of the closed group. EZ-NFL (P = 0.015), EZ-GCL (P = 0.004), EZ-INL (P < 0.001), EZ-OPL (P < 0.001), EZ-ONL (P < 0.001), Basal (P = 0.023) and Basal-NFL (P < 0.001) angles of hole-unclosed patients enlarged significantly after the surgery. CONCLUSIONS: Patients with large macular holes and an increased EZ-related angle and angle AR are more likely to experience unsuccessful outcomes following primary MH surgery. Therefore, EZ-related angles hold potential as valuable parameters for predicting the surgical outcome.


Assuntos
Perfurações Retinianas , Humanos , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgia , Estudos de Casos e Controles , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia , Membrana Basal/cirurgia
11.
Aging Clin Exp Res ; 35(2): 311-321, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36399323

RESUMO

BACKGROUND: The objective is to explore the value of preoperative geriatric nutritional risk index (GNRI) in evaluating long-term prognosis in elderly locally advanced rectal cancer (LARC) patients who accepted neoadjuvant chemoradiotherapy (NCRT) and to compare GNRI with established nutritional markers, including prognostic nutritional index (PNI) and controlling nutritional status (CONUT) score. METHODS: Preoperative GNRI was retrospectively assessed in 172 LARC patients aged ≥ 60 years who underwent radical resection after NCRT at two centers. Optimal cutoff value of GNRI was determined by X-tile program. The association of GNRI with clinicopathological parameters and nutritional markers was analyzed. The survival ability of markers was evaluated using time-dependent receiver-operating characteristic (ROC) curve analysis. Finally, survival analysis was performed using Kaplan-Meier and Cox regression analysis. RESULTS: GNRI was highly correlated with nutritional markers. An optimal cutoff value for the GNRI was 96. In the time-dependent ROC curve, GNRI demonstrated a stable predictive ability for both disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that GNRI was the only nutritional marker that independently predicted DFS (HR 2.457, 95% CI 1.066-5.665, P = 0.035) and OS (HR 9.002, 95% CI 3.100-26.146, P < 0.001). As an additional benefit, GNRI was able to stratify survival in subgroups of ypTNM and tumor response. CONCLUSION: Preoperative GNRI is a promising predictor of long-term survival for elderly LARC patients undergoing NCRT, superior to the established nutritional markers.


Assuntos
Estado Nutricional , Neoplasias Retais , Idoso , Humanos , Estudos Retrospectivos , Prognóstico , Avaliação Nutricional , Neoplasias Retais/cirurgia , Avaliação Geriátrica , Fatores de Risco
12.
Eye Contact Lens ; 49(9): 399-403, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37471255

RESUMO

OBJECTIVES: To assess the efficacy of orthokeratology in controlling the rate of myopia progression in children and investigate the factors associated with axial length (AL) growth rate with an average of 48 months of orthokeratology lens wear. METHODS: As a retrospective study, 84 subjects underwent relatively complete ophthalmologic examinations. After initial lens wear, AL was measured on average every 12 months. The linear mixed-effects model (LMM) was used to compare the differences in AL growth rates at each time interval. The contribution of the independent variables to AL change was assessed using multiple linear regression. RESULTS: In the LMM, there was a significant difference in the AL growth rate ( P <0.001) at each follow-up. The growth rate of AL was associated with initial AL, spherical equivalent refractive errors (SERs) and diameter of lens ( P =0.045, 0.003 and 0.037, respectively). When the baseline age was included as a factor, the influence of initial AL and SER became insignificant in the analysis, whereas age and diameter of lens were significantly correlated with the growth rate of AL ( P< 0.001 and P< 0.001, respectively). There were significant differences in growth rates among different age groups. CONCLUSIONS: Results of the study demonstrated that the factors associated with lower growth rate in AL were older age and longer diameter of lens.


Assuntos
Miopia , Procedimentos Ortoceratológicos , Criança , Humanos , Estudos Retrospectivos , Topografia da Córnea , Procedimentos Ortoceratológicos/métodos , Comprimento Axial do Olho , Miopia/terapia , Refração Ocular
13.
Phytochem Anal ; 34(8): 938-949, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37483127

RESUMO

INTRODUCTION: Citri Sarcodactylis Fructus has the effects of relieving cough, removing phlegm, and reducing asthma, but little is known about the metabolic and distribution of its chemical constituents in vivo. Therefore, it is necessary to study the metabolism of Citri Sarcodactylis Fructus in vivo. OBJECTIVE: We aimed to (1) analyze the distribution of prototype compounds and metabolites of the chemical constituents of Citri Sarcodactylis Fructus in rat and (2) infer the metabolites and metabolic pathways of the chemical constituents. MATERIALS AND METHODS: A C18 column (3 × 100 mm, 2.6 µm) was used. The mobile phase was water containing 0.1% formic acid (eluent A) and acetonitrile containing 0.1% formic acid (eluent B) at a discharge rate of 0.3 mL/min. Mass spectra of biological samples were collected in electrospray ionization (ESI) positive ion mode in the m/z 100-1500 scan range. The obtained biological samples were then subjected to chemical analysis, including plasma, urine, feces, and heart, liver, spleen, lungs, kidneys, stomach, and small intestine tissues. Prototype compounds and metabolites were identified. RESULTS: In all, 40 prototype compounds and 78 metabolites, including 26 phase I metabolites and 52 phase II metabolites, were identified using UHPLC-Q/Orbitrap HRMS. Eight possible metabolic pathways (reduction, hydrolysis, dehydration, methylation, hydroxylation, sulfation, glucuronidation, and demethylation) were proposed. The prototype compounds were predominantly distributed in lung tissues. The metabolites were mainly distributed in plasma and kidney tissues. CONCLUSION: We systematically investigated the metabolites of Citri Sarcodactylis Fructus in vivo. We suggest metabolic pathways that might be relevant for further metabolic studies and screening of active ingredients of Citrus Sarcodactylis Fructus in vivo.


Assuntos
Medicamentos de Ervas Chinesas , Ratos , Animais , Cromatografia Líquida de Alta Pressão , Formiatos , Espectrometria de Massas em Tandem
14.
Chin Med Sci J ; 38(1): 57-61, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37066727

RESUMO

We reported an 8-year-old boy with panscleritis in left eye and right epididymitis after falling on the ground. Etiologic diagnosis played a key role in this case. Systemic examinations ruled out systemic autoimmune diseases, tumors, and infections as the cause of scleritis and suggested that the disease was caused by a local delayed-type hypersensitivity (DTH) induced by ocular trauma and was non-infectious. Still, the right epididymitis was infectious. Both conditions were treated successfully using steroids and antibiotics, respectively. Thus, early etiologic diagnosis and reasonable treatment are crucial to prevent visual loss.


Assuntos
Epididimite , Traumatismos Oculares , Esclerite , Ferimentos não Penetrantes , Masculino , Humanos , Criança , Epididimite/etiologia , Epididimite/complicações , Traumatismos Oculares/complicações , Ferimentos não Penetrantes/complicações , Esclerite/tratamento farmacológico , Esclerite/etiologia , Face
15.
Int Ophthalmol ; 43(12): 4541-4549, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37668849

RESUMO

PURPOSE: In this study, we determined the positive rates of allergen-specific immunoglobulin E (IgE) in the tear fluid of Chinese patients with common allergic conjunctivitis (AC) in autumn and winter, compared systemic and ocular allergen tests, and explored the correlation between the numbers and categories of allergens and clinical AC features. METHODS: This cross-sectional study recruited 44 patients with AC (86 eyes). Specific IgEs for allergens common in China (house dust mite, cat/dog dander, mugwort/ragweed pollen, cottonwood/willow/elm pollen, milk, egg whites, soybeans) were measured in collected tears using kits for allergen-specific IgE antibodies. AC signs and symptoms were graded according to severity. RESULTS: Specific IgE in tears was positive in 87.2% of eyes. House dust mite was the most common allergen (86.0%), followed by cat (24.4%) and dog (7.0%) dander; tree and grass pollen accounted for only 4.7% and 2.3%, respectively. Food allergens were not detected. The positive rates of the systemic allergen tests were lower than in tear fluid tests in both eyes, especially for house dust mites (P = 0.000). In patients with more allergens, itching was more severe (P = 0.035), while conjunctival hyperemia was milder (P = 0.002). CONCLUSION: In autumn and winter, the most common AC allergen in Chinese patients was house dust mites. Compared with systemic allergen tests, measuring specific IgE in tears may be a non-invasive method to diagnose and evaluate AC severity, which may be more suitable to reflect the local conditions of ocular surface inflammation due to its high positive rate and convenience.


Assuntos
Conjuntivite Alérgica , Humanos , Animais , Cães , Conjuntivite Alérgica/diagnóstico , Estudos Transversais , Alérgenos , Pólen , Imunoglobulina E
16.
Int Ophthalmol ; 43(3): 779-793, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36056289

RESUMO

PURPOSE: To investigate corneal sub-basal nerve morphology changes in primary Sjogren's syndrome (SS) dry eye (SSDE) patients and determine the association with disease severity at microstructural level. METHODS: Twenty-eight eyes of 17 SSDE and 82 eyes of 47 age- and sex-matched non-SS dry eye (NSSDE) patients were included. The Ocular Surface Disease Index questionnaire (OSDI), Schirmer's test (ST), tear meniscus height (TMH), non-invasive breakup time (NIBUT), meibomian gland (MG) morphology, and ocular staining score (OSS) were assessed. In vivo confocal microscopy was performed to observe corneal sub-basal nerve morphology (length, reflectivity, width, and tortuosity). Associations between clinical features and nerve parameters were analysed. RESULTS: SSDE patients more frequently had increased nerve reflectivity (151.12 ± 17.07 vs. 139.37 ± 14.31 grey value), width (4.45 ± 0.87 vs. 3.92 ± 0.81 µm), tortuosity (132.90 ± 8.04 vs. 129.50 ± 7.33 degree), and higher reflectivity, width, and total nerve grades than NSSDE individuals (all P < 0.05). Significant associations were found between nerve reflectivity/width and anti-SSA [OR = 1.139 (1.013-1.281)/1.802 (1.013-4.465)]/labial gland biopsy [OR = 1.046 (1.002-1.161)/1.616 (1.020-3.243)]. Higher nerve width was associated with increased OSDI [ß = 0.284 (0.187-0.455)], MG score [ß = 0.185 (0.109-0.300)] and OSS [ß = 0.163 (0.020-0.345)], but decreased NIBUT [ß = - 0.247 (- 0.548 ~ - 0.154)]. Higher nerve total grade was associated with increased OSDI [ß = 0.418 (0.157-0.793)] and OSS [ß = 0.287 (0.027-0.547)], but decreased ST [ß = - 0.410 (-0.857 ~ - 0.138)]. CONCLUSIONS: Corneal nerve morphology changes associated with clinical features in SS patients. These changes may facilitate severity evaluation and management of the disease.


Assuntos
Síndromes do Olho Seco , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Lágrimas/química , Microscopia Confocal/métodos , Córnea/patologia , Síndromes do Olho Seco/etiologia , Síndromes do Olho Seco/complicações
17.
Semin Cancer Biol ; 71: 21-32, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32629077

RESUMO

Survival improvement of colorectal liver metastasis (CRLM) benefits from systemic therapy and metastasis-directed local therapy. Stereotactic ablative body radiotherapy (SABR), as a new efficient metastasis-directed local therapy with a systematic impact, plays a vital role in CRLM multidisciplinary treatment. SABR leads to a dramatic immunological change in the tumor microenvironment (TME) via differential activation of cytoprotective and cytotoxic pathways in malignant and non-malignant cells, in addition to direct tumor cell death. The synergy of SABR and immunotherapy might increase the abscopal response rate of out-field lesions by targeting different steps of the immune-mediated response, in addition to direct intratumoral cell death. The clinical treatment and efficacy of SABR, its influence on TME, and potential molecular underpinnings of which are the topic of this review.


Assuntos
Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/cirurgia , Radiocirurgia/métodos , Neoplasias Colorretais/patologia , Humanos , Neoplasias Hepáticas/secundário , Prognóstico
18.
BMC Genomics ; 23(1): 519, 2022 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-35842589

RESUMO

BACKGROUND: Skeletal muscles consist of fibers of differing contractility and metabolic properties, which are primarily determined by the content of myosin heavy chain (MYH) isoforms (MYH7, MYH2, MYH1, and MYH4). The regulation of Myh genes transcription depends on three-dimensional chromatin conformation interaction, but the mechanistic details remain to be determined. RESULTS: In this study, we characterized the interaction profiles of Myh genes using 4C-seq (circular chromosome conformation capture coupled to high-throughput sequencing). The interaction profile of Myh genes changed between fast quadriceps and slow soleus muscles. Combining chromatin immunoprecipitation-sequencing (ChIP-seq) and transposase accessible chromatin with high-throughput sequencing (ATAC-seq), we found that a 38 kb intergenic region interacting simultaneously with fast Myh genes promoters controlled the coordinated expression of fast Myh genes. We also identified four active enhancers of Myh7, and revealed that binding of MYOG and MYOD increased the activity of Myh7 enhancers. CONCLUSIONS: This study provides new insight into the chromatin interactions that regulate Myh genes expression.


Assuntos
Músculo Esquelético , Cadeias Pesadas de Miosina , Cromatina/genética , Cromatina/metabolismo , Expressão Gênica , Músculo Esquelético/metabolismo , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo
19.
Biochem Biophys Res Commun ; 608: 108-115, 2022 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-35397422

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer with poor clinical outcome. Poricoic acid A (PAA) is the main chemical constituent on the surface layer of the mushroom Poria cocos, and exerts protective effects against various diseases. In the study, its effects on T-ALL progression were investigated both in vitro and in vivo. Our results showed that PAA strongly reduced the cell viability of T-ALL cell lines, and induced cell G2 cycle arrest and apoptosis in vitro. Mitochondrial dysfunction was also elevated by PAA, along with enhanced cellular reactive oxygen species (ROS) production. Importantly, PAA-suppressed cell viability and -triggered apoptosis were ROS-dependent. Additionally, autophagy was significantly induced by PAA in T-ALL cells through regulating AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) and LC3 signaling pathways. PAA treatments also provoked ferroptosis in T-ALL cells with reduced glutathione (GSH) levels and elevated malonaldehyde (MDA) contents. Suppressing autophagy and ferroptosis almost abrogated the capacity of PAA to restrain T-ALL proliferation and growth. The effects of PAA to suppress T-ALL tumor growth were also confirmed in vivo with undetectable toxicity. Therefore, the present study highlighted the potential of PAA for T-ALL treatment mainly through inducing autophagic cell death and ferroptosis.


Assuntos
Morte Celular Autofágica , Ferroptose , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Apoptose , Autofagia , Linhagem Celular Tumoral , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Linfócitos T/metabolismo , Triterpenos
20.
Exp Eye Res ; 215: 108851, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34896307

RESUMO

We aimed to investigate the change patterns in corneal sub-basal nerve morphology and corneal intrinsic aberrations in dry eye disease (DED). Our study included 229 eyes of 155 patients with DED and 40 eyes of 20 healthy control. We used the Oculus keratograph and the ocular surface disease index questionnaire to assess their signs and symptoms. In vivo confocal microscopy was used to observe the corneal sub-basal nerves, corneal endothelial cells, and Langerhans cells (LCs). An artificial intelligence (AI) technique run by the deep learning model generated the sub-basal nerve fibre parameters. Furthermore, we used the Pentacam HR system to measure the corneal intrinsic aberrations and corneal surface regularity indices. DED patients more frequently had increased anterior and total corneal aberrations than controls (P < 0.05). In addition, DED had decreased average density and maximum length of corneal nerve. (Both P < 0.01) The LC number was significantly correlated with maximum length (CC = -0.19, P = 0.01) of the sub-basal nerve fibre. Furthermore, the corneal nerve average density was negatively correlated with IHD, and anterior, posterior, and total corneal aberrations (All P < 0.05) especially the higher-order aberrations. Significant correlations were seen between corneal nerve morphology changes, analysed by AI and corneal intrinsic aberrations, particularly higher-order aberrations.


Assuntos
Inteligência Artificial , Síndromes do Olho Seco , Córnea/inervação , Síndromes do Olho Seco/diagnóstico , Células Endoteliais , Humanos , Microscopia Confocal/métodos
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