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Abnormal osteoclast formation plays a significant part in rheumatoid arthritis (RA). As potent therapeutic biomarkers, microRNAs (miRNAs) have obtained increasing attention. Recently, treatment regimens regarding miRNAs have been implicated in skeletal diseases. The aim of this study is to assess the expression and function of miR-20a during osteoclast proliferation and differentiation and its correlation with bone erosion in RA mice. The expression of miR-20a was observed to be diminished in the ankle tissues of RA mice relative to that in normal controls evaluated by RT-qPCR. Hematoxylin and eosin staining, Safranin O-fast green staining, and tartrateresistant acid phosphatase staining were used to evaluate the effects of miR-20a on RA symptoms. The proliferation and differentiation of osteoclasts, and bone erosion were repressed by agomiR-20a injection. 3'UTR luciferase reporter assays were conducted to validate the putative binding between miR-20a and receptor activation of nuclear factor-κB ligand (RANKL). The protein expression and phosphorylation level of toll-like receptor4 (TLR4)/p38 pathway-related factors were detected by Western blot. miR-20a inhibited proliferation and differentiation potentials to osteoclasts partly through the TLR4/p38 pathway. The current work provides evidence that miR-20a hinders proliferation and differentiation of osteoclasts by targeting RANKL through the TLR4/p38 pathway.
Assuntos
Artrite Reumatoide , MicroRNAs , Animais , Artrite Reumatoide/genética , Diferenciação Celular , Ligantes , Sistema de Sinalização das MAP Quinases , Camundongos , MicroRNAs/genética , NF-kappa B , Osteoclastos , Osteogênese , Ligante RANK/genética , Receptor 4 Toll-Like/genéticaRESUMO
Objective: This report presents the initial outcomes of endoscopic intermuscular dissection (EID), a novel technique introduced by our team for the diagnostic resection of early rectal cancer, focusing on the postoperative status of the vertical margins. Methods: On January 26, 2024, a patient with early rectal cancer (cT1-2N0M0) underwent Endoscopic Intermuscular Dissection. The EID procedure consists of six steps: (1) mucosal incision; (2) submucosal dissection; (3) superficial muscular layer incision; (4) intermuscular dissection; (5) complete tumor removal; (6) wound management. Results: The patient was a 70-year-old male with rectal cancer (cT1-2N0M0). The tumor was located on the left anterior wall of the rectum, approximately 9 cm from the anal margin, and measured 20mm in size. The dissection rate was 2.68 mm²/minute, and the total duration of the surgery was 109 minutes. The patient was successfully discharged on the fifth day after surgery. Pathological examination of the post-endoscopic surgery specimen revealed pT1b, with negative vertical margins. Follow-up after more than one month showed good recovery with no complications such as bleeding, perforation, infection, or stricture occurring. Colonoscopy indicated the presence of a granulation tissue suggestive of inflammation. Conclusion: Endoscopic Intermuscular Dissection for the diagnostic resection of early rectal cancer is potentially safe and may achieve negative vertical margins.
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Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/diagnóstico , Idoso , Masculino , Ressecção Endoscópica de Mucosa/métodos , Dissecação/métodos , Reto/cirurgiaRESUMO
Objective: To explore the utility of stool-based DNA test of methylated SDC2 (mSDC2) for colorectal cancer (CRC) screening in residents of Shipai Town, Dongguan City. Methods: This was a cross-sectional study. Using a cluster sampling method, residents of 18 villages in Shipai Town, Dongguan City were screened for CRC from May 2021 to February 2022. In this study, mSDC2 testing was employed as a preliminary screening method. Colonoscopy examination was recommended for individuals identified as high-risk based on the positive mSDC2 tests. The final screening results, including the rate of positive mSDC2 tests, the rate of colonoscopy compliance, the rate of lesions detection, and the cost-effectiveness of screening, were analyzed to explore the benefits of this screening strategy. Results: A total of 10 708 residents were enrolled and completed mSDC2 testing, giving a participation rate of 54.99% (10 708/19 474) and a pass rate of 97.87% (10 708/10 941). These individuals included 4 713 men (44.01%) and 5 995 women (55.99%) with a mean age of (54.52±9.64) years. The participants were allocated to four age groups (40-49, 50-59, 60-69, and 70-74 years), comprising 35.21%(3770/10 708), 36.25% (3882/10 708), 18.84% (2017/10 708), and 9.70% (1039/10 708) of all participants, respectively. mSDC2 testing was positive in 821/10 708 (7.67%) participants, 521 of whom underwent colonoscopy, resulting in a compliance rate of 63.46% (521/821). After eliminating of 8 individuals without pathology results, data from 513 individuals were finally analyzed. Colonoscopy detection rate differed significantly between age groups (χ2=23.155, P<0.001),ranging from a low of 60.74% in the 40-49 year age group to a high of 86.11% in the 70-74 year age group. Colonoscopies resulted in the diagnosis of 25 (4.87%) CRCs, 192 (37.43%) advanced adenomas, 67 (13.06%) early adenomas, 15 (2.92%) serrated polyps, and 86 (16.76%) non- adenomatous polyps. The 25 CRCs were Stage 0 in 14 (56.0%) individuals, stage I in 4 (16.0%), and Stage II in 7(28.0%). Thus, 18 of the detected CRCs were at an early stage. The early detection rate of CRCs and advanced adenomas was 96.77% (210/217). The rate of mSDC2 testing for all intestinal lesions was 75.05% (385/513). In particular, the financial benefit of this screening was 32.64 million yuan, and the benefit-cost ratio was 6.0. Conclusion: Screening for CRCs using stool-based mSDC2 testing combined with colonoscopy has a high lesion detection rate and a high cost-effectiveness ratio. This is a CRC screening strategy that deserves to be promoted in China.
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Adenoma , Neoplasias Colorretais , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Transversais , Detecção Precoce de Câncer/métodos , Neoplasias Colorretais/patologia , Colonoscopia/métodos , Programas de Rastreamento/métodos , Adenoma/diagnóstico , DNA , Sindecana-2/genéticaRESUMO
UNLABELLED: The purpose of this study is to investigate the anti-osteoporotic effects of Radix Dipsaci total saponins (RTS). We showed that RTS was able to improve bone properties by either an increase of osteoblastic activity or a decrease in osteoclastic activity. INTRODUCTION: Radix Dipsaci has long been used as an anti-osteoporotic drug. The present study investigates the anti-osteoporotic effects of RTS. METHODS: Three-month-old female rats were randomly assigned into a sham-operated group (sham) and five ovariectomy (OVX) subgroups, namely, OVX with vehicle (OVX), OVX with 17ß-ethinylestradiol (E(2)), and OVX with graded doses of RTS (50, 100, or 200 mg/kg/d). RTS and E(2) were administered orally, daily from 1 week after OVX treatment for 4 months. Bone mass, turnover, and strength were evaluated by dual-energy X-ray absorptiometry, biochemical markers, and the three-point bending test. The trabecular bone microarchitecture was assessed by microCT. In vitro experiments were performed to determine the potential molecular mechanisms of the anti-osteoporotic effect of RTS. RESULTS: RTS prevented the loss of bone mass induced by OVX. The preventive effect on bone loss was primarily indicated by decreasing levels of bone turnover markers and confirmed by the changes in urinary calcium and phosphorus excretion. The treatment also enhanced the biomechanical strength of bone and prevented the deterioration of trabecular bone microarchitecture. RTS induced MC3T3-E1 and primary osteoblastic cell maturation and differentiation and increased bone formation by increasing BMP-2 synthesis. In addition, RTS inhibited osteoclastogenesis through an increase in osteoprotegrin and a decrease in NF-kB ligand expression in vitro. CONCLUSIONS: RTS treatment can effectively suppress the loss of bone mass induced by OVX and in vitro evidence suggests this could be through actions on both osteoblasts and osteoclasts.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Dipsacaceae , Medicamentos de Ervas Chinesas/uso terapêutico , Osteoporose/prevenção & controle , Saponinas/uso terapêutico , Animais , Peso Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Proteína Morfogenética Óssea 2/biossíntese , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Medicamentos de Ervas Chinesas/farmacologia , Estradiol/uso terapêutico , Feminino , Fêmur/diagnóstico por imagem , Fêmur/fisiopatologia , Tamanho do Órgão/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Osteoporose/diagnóstico por imagem , Osteoporose/patologia , Osteoporose/fisiopatologia , Osteoprotegerina/biossíntese , Ovariectomia , Fósforo/metabolismo , Ligante RANK/biossíntese , Ratos , Ratos Sprague-Dawley , Saponinas/farmacologia , Tomografia Computadorizada por Raios X , Regulação para Cima/efeitos dos fármacos , Útero/patologiaRESUMO
Despite broad interest in aluminum gallium nitride (AlGaN) optoelectronic devices for deep ultraviolet (DUV) applications, the performance of conventional Al(Ga)N planar devices drastically decays when approaching the AlN end, including low internal quantum efficiencies (IQEs) and high device operation voltages. Here we show that these challenges can be addressed by utilizing nitrogen (N) polar Al(Ga)N nanowires grown directly on Si substrate. By carefully tuning the synthesis conditions, a record IQE of 80% can be realized with N-polar AlN nanowires, which is nearly ten times higher compared to high quality planar AlN. The first 210 nm emitting AlN nanowire light emitting diodes (LEDs) were achieved, with a turn on voltage of about 6 V, which is significantly lower than the commonly observed 20 - 40 V. This can be ascribed to both efficient Mg doping by controlling the nanowire growth rate and N-polarity induced internal electrical field that favors hole injection. In the end, high performance N-polar AlGaN nanowire LEDs with emission wavelengths covering the UV-B/C bands were also demonstrated.
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Methylene chloride extracts of particulates from liquefied petroleum gas (LPG) combustion appliance were studied by using Ames test, micronucleus test and inducibility of pulmonary and hepatic aryl hydrocarbon hydroxylase (AHH) and glutathione S-transferase (GST) in rats. The extracts showed mutagenicity for Salmonella typhimurium strain TA98 and its derivatives TA98NR and TA98/1,8-DNP6 with or without S9 mix. The revertants in strains TA98NR and TA98/1,8-DNP6 were less than 40% and 50% of that in strain TA98 without S9 mix, respectively. Positive results were obtained in mouse bone marrow micronucleus assay. Intratracheal instillation of the extracts led to increase in pulmonary (but not hepatic) AHH and GST activities in rats. It was seen that AHH was more sensitive than GST to induction by the extracts.
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Mutagênicos/toxicidade , Petróleo/toxicidade , Animais , Hidrocarboneto de Aril Hidroxilases/biossíntese , Biotransformação , Indução Enzimática , Feminino , Glutationa Transferase/biossíntese , Fígado/enzimologia , Pulmão/enzimologia , Masculino , Camundongos , Testes para Micronúcleos , Ratos , Ratos Wistar , Salmonella typhimuriumRESUMO
The mutagenicity of urine from individuals exposed to the combustion products of liquefied petroleum gas (LPG) was detected with Salmonella typhimurium TA98 and its newly developed derivatives YG1021 (nitroreductase overproducing) and YG1024 (O-acetyltransferase overproducing). The detection showed significantly increased mutagenicity for the two YG strains and increased positive rates for all three strains in the presence of both rat liver S9 and beta-glucuronidase. Further analysis demonstrated that urine samples taken from smoking and non-smoking exposed individuals exhibited significantly higher mutagenic potency (revertants/10 microliters urine concentrate) than their corresponding controls. These results indicate that the increased urine mutagenicity is caused by the exposure to LPG combustion products or smoking. The mutagenic potency of urine samples of all exposed individuals tested with YG1024 was found to be about 7 times higher than with TA98. The difference in mutagenic potency was smaller for the same samples when comparison was made between YG1021 and TA98. This suggests that the mutagenic compounds present in the urine samples contain mainly aromatic compounds as glucuronide conjugates. Our results demonstrate that YG1024 is more sensitive than TA98 in detecting the mutagenicity of these samples. In addition, no significant difference in the mutagenic potency between the 'pure' exposed (non-smokers') and the 'pure' smokers' (unexposed) samples was found in all three tester strains. This might mean that the exposure extent of mutagens/carcinogens in LPG combustion products for exposed individuals roughly corresponds to the smoking level of smokers who smoke 20-40 cigarettes per day. Furthermore, the results also suggest that synergism might exist in the mutagenic effects of exposure to LPG combustion products and cigarette smoking.
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Óleos Combustíveis/toxicidade , Fumar/efeitos adversos , Urina/química , Adulto , Animais , Culinária , Humanos , Exposição por Inalação , Masculino , Testes de Mutagenicidade , Ratos , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Sensibilidade e EspecificidadeRESUMO
This report reviews the diagnosis, treatment and follow-up of 15 Chinese patients with tuberculous sacroiliitis (TBS) from 1997 to 2007. Buttock pain and lower back pain were the main complaints. All patients received antituberculosis chemotherapy treatment for at least 18 months; 10 also underwent surgery, with seven undergoing modified Smith-Petersen arthrodesis (evaluated using a visual analogue scale [VAS] for pain and the Oswestry Disability Index [ODI]). No simplex tuberculous synovitis existed at diagnosis. Bone-marrow oedema, cold abscess and soft-tissue oedema responded to antituberculosis treatment. Thirteen patients (86.7%) had satisfactory outcomes. There were also significant improvements in VAS and ODI scores post-operatively. In the chemotherapy plus surgery group, eight patients had solid bony fusions at 24 months post-operatively, while the five on chemotherapy alone presented with fibrous ankylosis at 24 months. Chemotherapy is the main treatment for TBS and modified arthrodesis is a feasible and effective method for treating severe joint destruction.
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Antituberculosos/uso terapêutico , Artrodese/métodos , Vértebras Lombares/patologia , Sacroileíte , Tuberculose Osteoarticular , Adolescente , Adulto , Anquilose/tratamento farmacológico , Anquilose/prevenção & controle , Anquilose/cirurgia , Antituberculosos/administração & dosagem , Edema/tratamento farmacológico , Edema/prevenção & controle , Edema/cirurgia , Feminino , Seguimentos , Humanos , Dor Lombar/tratamento farmacológico , Dor Lombar/prevenção & controle , Dor Lombar/cirurgia , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Estudos Retrospectivos , Sacroileíte/diagnóstico , Sacroileíte/tratamento farmacológico , Sacroileíte/cirurgia , Resultado do Tratamento , Tuberculose Osteoarticular/diagnóstico , Tuberculose Osteoarticular/tratamento farmacológico , Tuberculose Osteoarticular/cirurgiaRESUMO
General characteristics of waxes, adhesives and lubricants as well as the recent fundamental investigations on their physical and mechanical behaviour are introduced. The current R&D status for new type/generation of waxes, adhesives and lubricants from natural products is reviewed, with an emphasis on their tribological applications. In particular, some crucial issues and challenges relating to technological improvement and materials development are discussed. Based on the current predicted shortage of energy resources and environmental concerns, prospective research on the development of green waxes, adhesives and lubricants is suggested.
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Little is known about assembly of non-primate foamy virus (FV) such as bovine foamy virus (BFV). To help determine the requirements for assembly of BFV, we constructed BFV-Gag expression plasmids containing all or part of the gag gene, with or without modification by addition of myristate (Myr). Each construct was transfected alone, and with pFenv, into Sf-9 insect cells. The results showed that only the entire Gag could transit through nucleus, which is required for BFV viral assembly in the cytoplasm. Unlike other retroviruses (but like primate foamy viruses), BFV requires the coexpression of the Env protein for viral particle budding. In the case of BFV, this occurs at the plasma membrane rather than the endoplasmic reticulum (ER), due to lack of a functional ER retrieval signal (ERRS). The results also showed that addition of a Myr-membrane targeting signal to the C-terminus of Gag could restore the budding from plasma membrane, implying that Myr-membrane targeting signal could substitute for Env protein in budding.