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1.
Chemistry ; : e202402716, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39167361

ABSTRACT

Dithiocarbamate is a key structural sequence in pharmaceuticals and agrochemicals, and its synthesis is crucial in organic chemistry. Although significant progress has been made in related synthesis research, developing a practical and universal synthesis method remains fascinating. Herein, we report a new visible-light-induced decarboxylation coupling reaction between N-hydroxyphthalimide esters and tetraalkylthiuram disulfides, which uses Ir(ppy)3 as a photocatalyst to promote the generation of corresponding decarboxylation thioacylation product-dithiocarbamates in high yields. This redox-neutral protocol uses inexpensive and readily available starting material under mild reaction conditions, exhibiting broad substrate scope and wide functional group compatibility. This method can be further used for post modification of complex natural products and bioactive drugs.

2.
Front Endocrinol (Lausanne) ; 15: 1453601, 2024.
Article in English | MEDLINE | ID: mdl-39175578

ABSTRACT

Background: The presence of lymph node metastasis (LNM) is frequently observed in papillary thyroid carcinoma (PTC), and most clinical guidelines recommend total thyroidectomy. However, the impact of LNM on specific types of locoregional recurrence remains uncertain, particularly for stage T1 PTC. Methods: The present retrospective cohort study enrolled patients diagnosed with stage T1 PTC between 2008 and 2015. Propensity score matching was performed in patients with lobectomy accompanied by varying degrees of LNM. Logistic regression analysis was performed to compare the effect of LNM on relapse types, and Kaplan-Meier method was utilized to calculate recurrence-free survival. Results: The study cohort comprised 2,785 patients who were followed up for an average duration of 69 months. After controlling follow-up time and potential prognostic factors, we include a total of 362 patients in each group. Recurrence rates in the N0, N1a, and N1b groups were found to be 2.5%, 9.7%, and 10.2% respectively. Notably, group N1a versus group N0 (P=0.803), N1b group versus N0 group (P=0.465), and group N1b versus group N1a (P=0.344) had no difference in residual thyroid recurrence. However, when considering lymph node recurrence, both N1a(P=0.003) and N1b(P=0.009) groups showed a higher risk than N0 group. In addition, there was no difference in lymph node recurrence between N1b group and N1a group (P=0.364), but positive lymph node (PLN) and lymph node positive rate (LNPR) demonstrated a strong discriminatory effect (P<0.001). Conclusion: Lobectomy may be more appropriate for patients with unilateral stage T1 PTC in the low LNPR group.


Subject(s)
Lymphatic Metastasis , Neoplasm Recurrence, Local , Neoplasm Staging , Thyroid Cancer, Papillary , Thyroid Neoplasms , Thyroidectomy , Humans , Male , Female , Thyroidectomy/methods , Thyroid Cancer, Papillary/surgery , Thyroid Cancer, Papillary/pathology , Retrospective Studies , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Middle Aged , Adult , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Follow-Up Studies , Prognosis , Treatment Outcome , Lymph Nodes/pathology , Lymph Nodes/surgery
3.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(4): 611-620, 2024 Apr 28.
Article in English, Chinese | MEDLINE | ID: mdl-39019790

ABSTRACT

OBJECTIVES: The antimicrobial resistance of Staphylococcus aureus (S. aureus) has become a challenge in the treatment of infectious diseases. It is of great clinical value to discovery effective antimicrobial agents against multi-drug resistant S. aureus and its biofilms. This study aims to explore the antibacterial activity of the antiparasitic drug closantel against methicillin-resistant S. aureus and its biofilms through drug repurposing. METHODS: The sensitivity of S. aureus to closantel was assessed using microbroth dilution and disk diffusion methods. The bacteriostatic and bactericidal activities of closantel were determined by time-kill curves and colony count. Scanning electron microscopy combined with SYTOX Green and DiSC3(5) fluorescence probes were used to study the bactericidal mechanism of closantel. The influence of resistance was assessed by continuous exposure to sub-inhibitory concentrations of closantel. The anti-biofilm activity was evaluated using 96-well plates and crystal violet staining, and cytotoxicity was measured using the CCK-8 assay. RESULTS: The minimal inhibitory concentration (MIC) of closantel for both methicillin-sensitive and methicillin-resistant S. aureus ranged from 0.125 to 1.000 µg/mL. Disk diffusion tests showed that 80 µg of closantel created an inhibition zone, which increased in diameter with higher drug amounts. Sub-inhibitory concentrations (0.031 µg/mL) of closantel significantly inhibited S. aureus proliferation, reducing bacterial turbidity from 0.26±0.00 to 0.11±0.01 (t=16.06, P<0.001), with stronger inhibition at higher concentrations. Closantel at 0.25×MIC inhibited S. aureus proliferation for 12 hours, while 1×MIC inhibited it for over 24 hours, with the number of viable bacteria decreasing as the drug concentration increased. Mechanistic studies indicated that closantel effectively disrupted the integrity of S. aureus cell membranes, significantly increasing SYTOX Green and DiSC3(5) fluorescence intensity. Even after 25 days of continuous exposure to sub-inhibitory concentrations of closantel, no resistance developed. Closantel at 0.0625 µg/mL significantly inhibited biofilm formation, reducing it from 1.29±0.16 to 0.62±0.04 (t=11.62, P<0.001), showing a clear dose-dependent effect. Closantel at 2 µg/mL also significantly eradicated established biofilms, reducing biofilm mass from 1.62±0.34 to 0.51±0.39 (t=4.84, P<0.01). Additionally, closantel exhibited extremely low cytotoxicity, with half-maximal lethal concentrations for HepG2 liver cancer cells and normal LO2 liver cells both exceeding 64 µg/mL. CONCLUSIONS: Closantel exhibits strong antibacterial activity against S. aureus and its biofilm with low cytotoxicity against human cells, making it a promising candidate for new therapeutic strategies against S. aureus-related infections.


Subject(s)
Anti-Bacterial Agents , Biofilms , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Salicylanilides , Biofilms/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Salicylanilides/pharmacology
4.
Biomedicines ; 12(7)2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39062109

ABSTRACT

Septic encephalopathy (SE) represents a severe inflammatory syndrome linked to elevated septic mortality rates, lacking specific therapeutic interventions, and often resulting in enduring neurological sequelae. The present investigation endeavors to elucidate the involvement of C-X-C Motif Chemokine Receptor 2 (CXCR2) in the pathogenesis of SE and to explore the potential of CXCR2 modulation as a therapeutic avenue for SE. Employing a murine SE model induced by lipopolysaccharide (LPS) administration, CXCR2 knockout mice and the CXCR2 inhibitor SB225002 were utilized to assess neutrophil recruitment, endothelial integrity, and transendothelial migration. Our findings substantiate that either CXCR2 deficiency or its inhibition curtails neutrophil recruitment without impacting their adhesion to cerebral endothelial cells. This phenomenon is contingent upon endothelial CXCR2 expression rather than CXCR2's presence on neutrophils. Furthermore, the CXCR2 blockade preserves the integrity of tight junction protein ZO-1 and mitigates F-actin stress fiber formation in cerebral endothelial cells following septic challenge. Mechanistically, CXCL1-mediated CXCR2 activation triggers cerebral endothelial actin contraction via Rho signaling, thereby facilitating neutrophil transmigration in SE. These observations advocate for the potential therapeutic efficacy of CXCR2 inhibition in managing SE.

5.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39016698

ABSTRACT

"Molecular ping-pong," emerging as a control strategy in solid-state nanopore technology, presents a highly promising approach for repetitive measurements of single biomolecules, such as DNA. This paper introduces a high-precision, high-speed nanopore molecular ping-pong control system consisting of a home-built trans-impedance amplifier (TIA), a control system based on a Field Programmable Gate Array (FPGA), and a LabVIEW program operating on the host personal computer. Through feedback compensation and post-stage boosting, the TIA achieves a high bandwidth of about 200 kHz with a gain of 100 MΩ, along with low input-referred current noise of 1.6 × 10-4 pA2/Hz at 1 kHz and 1.1 × 10-3 pA2/Hz at 100 kHz. The FPGA-based control system demonstrates a minimum overall response time (tdelay) of 6.5 µs from the analog input current signal trigger to the subsequent reversal of the analog output drive voltage signal, with a control precision of 1 µs. Additionally, a LabVIEW program has been developed to facilitate rapid data exchange and communication with the FPGA program, enabling real-time signal monitoring, parameter adjustment, and data storage. Successful recapture of individual DNA molecules at various tdelay, resulting in an improvement in capture rate by up to 2 orders of magnitude, has been demonstrated. With unprecedented control precision and capture efficiency, this system provides robust technical support and opens novel research avenues for nanopore single-molecule sensing and manipulation.

6.
Chem Commun (Camb) ; 60(59): 7614-7617, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-38957034

ABSTRACT

A mild and efficient electrochemical method for radical addition, cyclization, and migration reaction was described in this work. A difluoromethyl radical was produced by anodizing CF2HSO2Na. The resulting product was then added to olefin, underwent Smiles cyclization, and migrated to form ß-difluoromethamide compounds after the release of SO2. The process was free from metals and catalysts, gram-grade, and resistant to a variety of electron-rich substrates.

7.
Chem Sci ; 15(28): 10989-10996, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39027270

ABSTRACT

The discovery of negative differential conductance (NDC) in a single molecule and mechanism controlling this phenomenon are important for molecular electronics. We investigated the electronic properties of a typical radical molecule 3-carbamoyl-2,2,5,5-tetramethyl-3-pyrrolin-1-yloxy (CTPO) on an Au(111) surface using low-temperature scanning tunneling microscopy (STM) and inelastic electron tunneling spectroscopy. Large NDC was observed in single CTPO molecules at the boundary of the crystal monolayer. The origin of observed NDC is revealed as the inelastic electron-phonon scattering during tunneling, and the strong spatial variation of the NDC over the single molecule illustrates the nature of the localized radical group. In addition, the NDC can be transformed into a positive differential conductance peak by tuning coupling strengths between different tunneling channels. An empirical multi-channel model has been developed to describe the competition between the valley-shaped NDC and peak-shaped positive differential conductance. The unique electronic property and giant conductance change observed in this radical molecule is valuable for designing novel molecular devices in the future.

8.
BMC Med Educ ; 24(1): 513, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720325

ABSTRACT

INTRODUCTION: Exercise enhances one's health and competitiveness. A strong physical fitness status can pave the way for a promising future. This study presents the time-based trends in physical fitness indicators-including height, weight, BMI, lung capacity, dash, long-distance running, and standing long jump-among medical undergraduates during their university years. Additionally, we analyzed the impact of students' physical fitness on their career paths. METHOD: We conducted a retrospective database study by collecting physical fitness test data and career paths information for 634 medical students from a university in southwestern China. These students graduated in 2022. The career paths included pursuits in further studies, employment, and unemployment. To detect differences in these aspects, we used the t-test and Chi-square test. RESULTS: Our study indicates a significant declining trend in the physical fitness of medical students during their university years. The changes observed between the first and fourth tests are as follows: Weight (kg): 58.52 ± 10.48 to 60.73 ± 12.07, P < 0.00 BMI (kg/m^2): 20.79 ± 2.74 to 21.24 ± 3.06, P < 0.00 50-m dash (s): 8.91 ± 0.99 to 9.25 ± 1.11, P < 0.00 Standing long jump (cm): 187.74 ± 30.98 to 182.59 ± 32.25, P < 0.00 800-m run for females (min): 3.84 ± 0.47 to 4.48 ± 0.85, P < 0.00 1000-m run for males (min): 3.98 ± 0.63 to 4.62 ± 0.87, P < 0.00 Sit-ups for females (count): 30.39 ± 7.5 to 29.03 ± 8.82, P < 0.00 Upon analyzing the correlation between changes in physical fitness and career paths, students with stable or decreased BMI had better post-graduation outcomes compared to students with increased BMI. CONCLUSIONS: Medical students show a declining trend in physical fitness during their undergraduate years. A good physical health status is beneficial for achieving better career paths. Medical students should place greater emphasis on physical exercise during their time in school.


Subject(s)
Physical Fitness , Students, Medical , Humans , Male , Female , Longitudinal Studies , Retrospective Studies , China , Young Adult , Career Choice , Adult , Body Mass Index , Education, Medical, Undergraduate
9.
Phytomedicine ; 130: 155642, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38759315

ABSTRACT

BACKGROUND: Huangkui capsule (HKC), as an ethanol extract of Abelmoschus manihot (L.), has a significant efficacy in treatment of the patients with diabetic kidney disease (DKD). The bioactive ingredients of HKC mainly include the flavonoids such as rutin, hyperoside, hibifolin, isoquercetin, myricetin, quercetin and quercetin-3-O-robinobioside. PURPOSE: To explore the molecular mechanisms of A. manihot in treatment of DKD. STUDY DESIGN: A single-cell RNA sequencing analysis of kidneys in db/db mice with and without HKC administration. METHODS: Urinary biochemical and histopathological examination in C57BL/6 and db/db mice of DKD and HKC groups was done. Single-cell RNA sequencing pipeline was then performed. The regulatory mechanisms of seven flavonoids in HKC were revealed by cell communication, prediction of transcription factor regulatory network, and molecular docking. RESULTS: By constructing ligand-receptor regulatory network and performing molecular docking between 75 receptors with different activities and seven flavonoids. 11 key receptors in 4 cell types (segment 3 proximal convoluted tubular cell, ascending limbs of the loop of Henle, distal convoluted tubule, and T cell) in kidneys were found to be directly interacted with HKC. The interactions regulated 8 downstream regulons. The docking receptors in T cell led to transcriptional event differences in the regulons such as Cebpb, Rel, Tbx21 and Klf2 and consequently affected the activation, differentiation, and infiltration of T cell, while the receptors Tgfbr1 and Ldlr in stromal cells of kidneys were closely associated with the downstream transcriptional events of renal injury and proteinuria in DKD. CONCLUSION: The current study provides novel information of the key receptors and regulons in renal cells for a better understanding of the cell type specific molecular mechanisms of A. manihot in treatment of DKD.


Subject(s)
Abelmoschus , Diabetic Nephropathies , Flavonoids , Mice, Inbred C57BL , Molecular Docking Simulation , Abelmoschus/chemistry , Diabetic Nephropathies/drug therapy , Animals , Flavonoids/pharmacology , Male , Mice , Kidney/drug effects , Single-Cell Analysis , Receptor, Transforming Growth Factor-beta Type I/metabolism , Gene Expression Regulation/drug effects , Drugs, Chinese Herbal/pharmacology , Plant Extracts/pharmacology
11.
Angew Chem Int Ed Engl ; 63(27): e202404295, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38649323

ABSTRACT

Homogeneous electrocatalysts can indirect oxidate the high overpotential substrates through single-electron transfer on the electrode surface, enabling efficient operation of organic electrosynthesis catalytic cycles. However, the problems of this chemistry still exist such as high dosage, difficult recovery, and low catalytic efficiency. Single-atom catalysts (SACs) exhibit high atom utilization and excellent catalytic activity, hold great promise in addressing the limitations of homogeneous catalysts. In view of this, we have employed Fe-SA@NC as an advanced redox mediator to try to change this situation. Fe-SA@NC was synthesized using an encapsulation-pyrolysis method, and it demonstrated remarkable performance as a redox mediator in a range of reported organic electrosynthesis reactions, and enabling the construction of various C-C/C-X bonds. Moreover, Fe-SA@NC demonstrated a great potential in exploring new synthetic method for organic electrosynthesis. We employed it to develop a new electro-oxidative ring-opening transformation of cyclopropyl amides. In this new reaction system, Fe-SA@NC showed good tolerance to drug molecules with complex structures, as well as enabling flow electrochemical syntheses and gram-scale transformations. This work highlights the great potential of SACs in organic electrosynthesis, thereby opening a new avenue in synthetic chemistry.

12.
J Gastroenterol Hepatol ; 39(4): 658-666, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38251791

ABSTRACT

BACKGROUND AND AIM: Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS: This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS: A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION: This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.


Subject(s)
Amines , Esophagitis, Peptic , Gastroesophageal Reflux , Peptic Ulcer , Pyrroles , Humans , Double-Blind Method , Esomeprazole/adverse effects , Esophagitis, Peptic/drug therapy , Esophagitis, Peptic/etiology , Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/complications , Peptic Ulcer/complications , Proton Pump Inhibitors/adverse effects , Treatment Outcome
13.
Small ; 20(4): e2304336, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37712103

ABSTRACT

Recently, metal 1halide perovskites have shown compelling optoelectronic properties for both light-emitting devices and scintillation of ionizing radiation. However, conventional lead-based metal halide perovskites are still suffering from poor material stability and relatively low X-ray light yield. This work reports cadmium-based all-inorganic metal halides and systematically investigates the influence of the metal ion incorporation on the optoelectronic properties. This work introduces the bi-metal ion incorporation strategy and successfully enhances the photoluminescence quantum yield (98.9%), improves thermal stability, and extends the photoluminescence spectra, which show great potential for white light emission. In addition, the photoluminescent decay is also modulated with single metal ion incorporation, the charge carrier lifetime is successfully reduced to less than 1 µs, and the high luminescent efficiency and X-ray light yield (41 000 photons MeV-1 ) are maintained. Then, these fast scintillators are demonstrated for high-speed light communication and sensitive X-ray detection and imaging.

14.
Clin Cancer Res ; 30(1): 127-138, 2024 01 05.
Article in English | MEDLINE | ID: mdl-37931242

ABSTRACT

PURPOSE: Medullary thyroid carcinoma (MTC) presents a distinct biological context from other thyroid cancers due to its specific cellular origin. This heterogeneous and rare tumor has a high prevalence of advanced diseases, making it crucial to address the limited therapeutic options and enhance complex clinical management. Given the high clinical accessibility of methylation information, we construct the largest MTC methylation cohort to date. EXPERIMENTAL DESIGN: Seventy-eight fresh-frozen MTC samples constituted our methylation cohort. The comprehensive study process incorporated machine learning, statistical analysis, and in vitro experiments. RESULTS: Our study pioneered the identification of a three-class clustering system for risk stratification, exhibiting pronounced epigenomic heterogeneity. The elevated overall methylation status in MTC-B, combined with the "mutual exclusivity" of hypomethylated sites displayed by MTC-A and MTC-C, distinctively characterized the MTC-specific methylation pattern. Integrating with the transcriptome, we further depicted the features of these three clusters to scrutinize biological properties. Several MTC-specific aberrant DNA methylation events were emphasized in our study. NNAT expression was found to be notably reduced in poor-prognostic MTC-C, with its promoter region overlapping with an upregulated differentially methylated region. In vitro experiments further affirmed NNAT's therapeutic potential. Moreover, we built an elastic-net logistic regression model with a relatively high AUC encompassing 68 probes, intended for future validation and systematic clinical application. CONCLUSIONS: Conducting research on diseases with low incidence poses significant challenges, and we provide a robust resource and comprehensive research framework to assist in ongoing MTC case inclusion and facilitate in-depth dissection of its molecular biological features.


Subject(s)
Carcinoma, Neuroendocrine , Thyroid Neoplasms , Humans , DNA Methylation , Thyroid Neoplasms/pathology , Carcinoma, Neuroendocrine/pathology
15.
Adv Sci (Weinh) ; 11(7): e2308238, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38064182

ABSTRACT

Alkenylboronates are highly versatile building blocks and valuable reagents in the synthesis of complex molecules. Compared with that of monosubstituted alkenylboronates, the synthesis of multisubstituted alkenylboronates is challenging. The copper-catalyzed carboboration of alkynes is an operationally simple and straightforward method for synthesizing bis/trisubstituted alkenylboronates. In this work, a series of copper-metallized N-Heterocyclic Carbene (NHC) ligand porous polymer catalysts are designed and synthesized in accordance with the mechanism of carboboration. By using CuCl@POL-NHC-Ph as the optimal nanocatalyst, this study realizes the ß-regio- and stereoselective (syn-addition) 1,2-carboboration of alkynes (regioselectivity up to >99:1) with satisfactory yields and a wide range of substrates. This work not only overcomes the selectivity of carboboration but also provides a new strategy for the design of nanocatalysts and their application in organic synthesis.

16.
Angew Chem Int Ed Engl ; 63(3): e202315032, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38057563

ABSTRACT

The oxygen evolution reaction (OER), characterized by a four-electron transfer kinetic process, represents a significant bottleneck in improving the efficiency of hydrogen production from water electrolysis. Consequently, extensive research efforts have been directed towards identifying single-atom electrocatalysts with exceptional OER performance. Despite the comprehensive understanding of the OER mechanism, its application to other valuable synthetic reactions has been limited. Herein, we leverage the MOOH intermediate, a key species in the Mn-N-C single-atom catalyst (Mn-SA@NC), which can be cyclically delivered in the OER. We exploit this intermediate' s capability to facilitate electrophilic transfer with silane, enabling efficient silane oxidation under electrochemical conditions. The SAC electrocatalytic system exhibits remarkable performance with catalyst loadings as low as 600 ppm and an exceptional turnover number of 9132. Furthermore, the catalytic method demonstrates stability under a 10 mmol flow chemistry setup. By serving as an OER electrocatalyst, the Mn-SA@NC drives the entire reaction, establishing a practical Mn SAC-catalyzed organic electrosynthesis system. This synthesis approach not only presents a promising avenue for the utilization of electrocatalytic OER but also highlights the potential of SACs as an attractive platform for organic electrosynthesis investigations.

17.
Org Lett ; 26(1): 193-197, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38147844

ABSTRACT

In this study, a multicomponent reaction via the Mannich intermediate was developed using methanol, secondary amine, and sulfonamide as starting materials. This method uses methanol as a green C1 source. The substrate scope is wide, and the yield is good. The mechanistic study shows that methanol generates formaldehyde under electrochemical conditions, and sulfonyl amidine as a nucleophile reacts with Schiff base intermediates to form N-sulfonyl amidine in a single step.

18.
Cytokine ; 173: 156442, 2024 01.
Article in English | MEDLINE | ID: mdl-37995395

ABSTRACT

PURPOSE: The characteristics of cytokine/chemokine(CK) profiles across different courses of chronic hepatitis B virus infection and the effects of NAs antiviral therapy on cytokine profiles remain unclear. METHODS: This report provides evidence from 383 patients with chronic HBV infection. The Luminex multiple cytokine detection technology was used to detect CK profiles. The predictive power of CKs across course of disease was assessedusing univariate analyses and with receiver operating characteristic (ROC) curves. RESULTS: Compared to healthy control (HC), expression levels of interleukin 6 (IL)-6, IL-8, IL-21, matrix metalloproteinases (MMP)-2 and tumor necrosis factor receptor (TNFR)-1 showed a significant increasing trend during chronic HBV infection. IL-23 and IL-33 increased respectively in chronic hepatitis B patients (CHB). interferon (IFN)-gamma and TNF-α changed significantly only in liver cirrhosis (LC) patients. Whereas, myeloid-related markers decreased dramatically in those with hepatocellular carcinoma (HCC). The ROC result suggests that combining IL-6, IL-8, CXCL9 and CXCL13 into a nomogram has closely correlation with HCC during chronic HBV infection. In addition, nucleotide analogues (NAs) antiviral treatments are capable of recoveringnormal liver functions and significantly reducing the viral loads, however, they seem to have a limited effect in changing CKs, especially specific antiviral factors. CONCLUSION: The differential CK and virological markers may serve as potential indicators of distinct immune statuses in chronic HBV infection. They also underscore the varying efficacy and limitations of NAs antiviral therapies. This next step would to break new ground in the optimization of current anti-HBV treatment programs although this requires further research.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B, Chronic , Liver Neoplasms , Humans , Hepatitis B virus , Nucleotides , Interleukin-8 , Cytokines/metabolism , Antiviral Agents/therapeutic use
19.
Biomed Pharmacother ; 169: 115899, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37984306

ABSTRACT

As a traditional Chinese medicine, Huangkui capsule (HKC) has been used to treat patients with kidney diseases, including diabetic nephropathy (DN). We have recently demonstrated that HKC could re-regulate the activities of solute carriers (SLC)s in proximal and distal convoluted tubules of kidneys in regression of the development of DN. The main active chemical constituents of HKC are the flavones of Abelmoschus manihot (L.). The current study aims to further evaluate the efficacy of total flavones of A. manihot (TFA) in the regression of DN by analyzing SLC activities in proximal and distal convoluted tubules of kidneys. TFA (0.076 g/kg/d) or vehicle was administered in db/db mice, the animal model of type 2 diabetes and DN, daily via oral gavage for four weeks. Blood glucose levels and urinary albumin-to-creatinine ratio (UACR) were measured and used for the determination of T2D and DN. Ten SLCs, including slc2a2, slc4A1, slc5a2, slc5A3, slc5a8, slc6a20, slc27a2, slc12a3, slc34a1 and slc38a2 were highly expressed in proximal and distinct convoluted tubules of kidneys. Their expression at mRNA and protein levels before and after TFA treatment were analyzed with real-time RT-PCR and immunohistochemistry. Data showed that UACR in the db/db mice after TFA treatment was significantly decreased. Compared with the group of non-diabetic control, slc2a2, slc4A1, slc5a2, slc5A3, slc5a8, slc6a20, slc27a2, slc12a3, slc34a1 and slc38a2 in the group of DN were down-regulated but up-regulated after TFA treatment. Further analyses of whole kidney sections indicated that the numbers and structures of the nephron in db/db mice was increased and improved after TFA treatment. Thereby, the current study provides further evidence that the flavones in A. manihot have pharmacological effects on the treatment of DN by improving the biological function of SLCs in kidneys.


Subject(s)
Abelmoschus , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Flavones , Humans , Rats , Mice , Animals , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/metabolism , Abelmoschus/chemistry , Flavones/pharmacology , Flavones/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Rats, Sprague-Dawley , Epithelial Cells
20.
Org Biomol Chem ; 21(39): 7895-7899, 2023 Oct 11.
Article in English | MEDLINE | ID: mdl-37747203

ABSTRACT

Aminophenols are a class of important compounds with various pharmacological activities such as anticancer, anti-inflammatory, antimalarial, and antibacterial activities. Herein, we introduce a mild and efficient electrochemical selenium-catalyzed strategy to synthesize polysubstituted aminophenols. High atom efficiency and transition metal-free and oxidant-free conditions are the striking features of this protocol. By merging electrochemical and organoselenium-catalyzed processes, the intramolecular rearrangement of N-aryloxyamides produces para-amination products at room temperature in a simple undivided cell.

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