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2.
World J Gastrointest Surg ; 16(6): 1775-1790, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38983337

RESUMO

BACKGROUND: Hepatitis is a systemic disease that often results in various comorbidities. Meta-bolic disorders, the most common comorbidities in clinical practice, were selected for this study. AIM: To investigate the causal relationship between comorbidities and hepatitis trea-tment outcomes. METHODS: A total of 23583378 single nucleotide polymorphisms from 1248743 cases and related summaries of genome-wide association studies were obtained from online public databases. A two-sample Mendelian randomization (MR) was performed to investigate causality between exposure [type 2 diabetes mellitus (T2D), hyperlipidemia, and hypertension] and outcome (chronic hepatitis B or C in-fections). RESULTS: The data supported the causal relationship between comorbidities and hepatitis infections, which will affect the severity of hepatitis progression and will also provide a reference for clinical researchers. All three exposures showed a link with progression of both hepatitis B (T2D, P = 0.851; hyperlipidemia, P = 0.596; and hypertension, P = 0.346) and hepatitis C (T2D, P = 0.298; hyperlipidemia, P = 0.141; and hypertension, P = 0.035). CONCLUSION: The results of MR support a possible causal relationship between different ex-posures (T2D, hyperlipidemia, and hypertension) and chronic hepatitis progression; however, the potential mechanisms still need to be elucidated.

3.
World J Clin Cases ; 12(18): 3368-3377, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38983410

RESUMO

BACKGROUND: With advancements in the diagnosis and treatment of lung diseases, lung segment surgery has become increasingly common. Postoperative rehabilitation is critical for patient recovery, yet challenges such as complications and adverse outcomes persist. Incorporating humanized nursing modes and novel treatments like nitric oxide inhalation may enhance recovery and reduce postoperative complications. AIM: To evaluate the effects of a humanized nursing mode combined with nitric oxide inhalation on the rehabilitation outcomes of patients undergoing lung surgery, focusing on pulmonary function, recovery speed, and overall treatment costs. METHODS: A total of 79 patients who underwent lung surgery at a tertiary hospital from March 2021 to December 2021 were divided into a control group (n = 39) receiving a routine nursing program and an experimental group (n = 40) receiving additional humanized nursing interventions and atomized inhalation of nitric oxide. Key indicators were compared between the two groups alongside an analysis of treatment costs. RESULTS: The experimental group demonstrated significant improvements in pulmonary function, reduced average recovery time, and lower total treatment costs compared to the control group. Moreover, the quality of life in the experimental group was significantly better in the 3 months post-surgery, indicating a more effective rehabilitation process. CONCLUSION: The combination of humanized nursing mode and nitric oxide inhalation in postoperative care for lung surgery patients significantly enhances pulmonary rehabilitation outcomes, accelerates recovery, and reduces economic burden. This approach offers a promising reference for improving patient care and rehabilitation efficiency following lung surgery.

4.
Adv Mater ; : e2405502, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38885327

RESUMO

The development of bioorthogonal activation in drug release represents a promising avenue for precise and safe anticancer treatment. However, two significant limitations currently hinder their clinical application: i) the necessity for separate administration of the drug precursor and its corresponding activator, leading to poor drug accumulation and potential side effects; ii) the reliance on exogenous metal or organic activators for triggering bioorthogonal activation, which often exhibit low efficiency and systemic toxicity when extending to living animals. To overcome these limitations, a nitric oxide (NO)-mediated bioorthogonal codelivery nanoassembly, termed TTB-NH2@PArg, which comprises a precursor molecular (TTB-NH2) and amphipathic polyarginine (PArg) is developed. In TTB-NH2@PArg, PArg serves as both self-assembled nanocarrier for TTB-NH2 and a NO generator. In tumor microenvironment (TME), the TME-specific generation of NO acts as a gas activator, triggering in situ bioorthogonal bond formation that transforms TTB-NH2 into TTB-AZO. This tumor-specific generation of TTB-AZO not only serves as a potential photothermal agent for effective tumor inhibition but also induces fluorescence change that enables real-time monitoring of bioorthogonal activation. This study presents a drug codelivery approach that enables precise and safe control of bioorthogonal activation for anticancer treatment, improving cancer therapy efficacy while minimizing side effects.

5.
Cell Discov ; 10(1): 70, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38937452

RESUMO

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants. TKD is composed of a KRAS-binding nanobody, a cell-penetrating peptide selectively targeting cancer cells, and a lysosome-binding motif. Our data revealed that TKD selectively binds to KRAS in cancer cells and effectively induces KRAS degradation via a lysosome-dependent process. Functionally, TKD suppresses tumor growth with no obvious side effects and enhances the antitumor effects of PD-1 antibody and cetuximab. This study not only provides a strategy for developing drugs targeting "undruggable" proteins but also reveals that TKD is a promising therapeutic for treating KRAS-mutant cancers.

6.
J Thorac Dis ; 16(5): 3142-3151, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38883638

RESUMO

Background: With the need for "actionable histology" in the current era of targeted cancer treatment, and the increasing practice of upfront thoracoscopy (without a prior diagnostic thoracentesis) or a "biopsy first" approach in suspected malignant pleural effusions (MPEs), we sought to prospectively evaluate the diagnostic accuracy, including full molecular profiling of cancer, and safety of medical thoracoscopy (MT) at a tertiary referral hospital. Methods: Patients with MT performed for an undiagnosed pleural effusion between January 2020 and December 2022 were included in this observational cohort study. All procedures were performed with a semirigid thoracoscope under conscious sedation. Clinical outcomes and adverse events were recorded prospectively. Results: We evaluated 141 patients, with a mean age of 67±12 years. Talc poudrage was performed in 67 (47.5%) patients with a median of 2 [interquartile range (IQR), 1-4] hospitalisation days after MT. Upfront thoracoscopy was performed in approximately half (55.3%) of patients. The overall diagnostic accuracy of MT was 95.7% in our cohort. A final diagnosis of cancer was made in 116 (82.3%) patients, with lung (67.2%) and breast cancer (8.6%) the most common. The diagnostic sensitivity of MT for malignancy was 94.8%, and molecular profiling of relevant cancer types for oncogenic mutations was achieved in all patients with malignancy seen on histopathology. The most common non-malignant diagnosis was tuberculous pleuritis in 14 patients (9.9%). Major complications occurred in 3 (2.1%) patients. Two patients had re-expansion pulmonary edema that resolved with low flow oxygen supplementation in the general ward, and one patient required intensive care unit admission for cardiac tamponade from a malignant pericardial effusion. There were no cases of mortality, bleeding complications or persistent air leaks. Conclusions: MT is a well-tolerated and effective option for the evaluation of undiagnosed pleural effusions. With expanding utility and expertise with MT and other pleural interventions, the challenge for respiratory physicians is integrating these into expeditious diagnostic and effective therapeutic pathways, individualised to patients' needs.

7.
PLoS One ; 19(5): e0298118, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38722833

RESUMO

It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression. This study included all eligible 156 cervical cancers diagnosed during 2003-2008 and followed up through 2014, 102 cervical intraepithelial neoplasia (CIN) patients, and 16 participants with normal cervix identified at the same period. Correlation of expression of TPP1 and hTERT in these lesions was assessed using Kappa statistics. TPP1 was knocked down by siRNA in three cervical cancer cell lines. We assessed mRNA expression using quantitative real-time polymerase chain reaction and protein expression using tissue microarray-based immunohistochemical staining. We further analyzed the impact of TPP1 expression on the overall survival of cervical cancer patients by calculating the hazard ratio (HR) with 95% confidence intervals (CIs) using the multivariable-adjusted Cox regression model. Compared to the normal cervix, high TPP1expression was significantly associated with CIN 3 and cervical cancers (P<0.001 for both). Expressions of TPP1 and hTERT were highly correlated in CIN 3 (Kappa statistics = 0.50, P = 0.005), squamous cell carcinoma (Kappa statistics = 0.22, P = 0.011), and adenocarcinoma/adenosquamous carcinoma (Kappa statistics = 0.77, P = 0.001). Mechanistically, knockdown of TPP1 inhibited the expression of hTERT in both mRNA and protein levels. High expression of TPP1 (HR = 2.61, 95% CI 1.23-5.51) and co-high expression of TPP1 and hTERT (HR = 2.38, 95% CI 1.28-4.43) were independently associated with worse survival in cervical cancer patients. TPP1 and hTERT expression was correlated and high expression of TPP1 was associated with high risk of CIN 3 and cervical cancer and could predict a worse survival in cervical cancer.


Assuntos
Complexo Shelterina , Telomerase , Proteínas de Ligação a Telômeros , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Telomerase/genética , Telomerase/metabolismo , Proteínas de Ligação a Telômeros/metabolismo , Proteínas de Ligação a Telômeros/genética , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/metabolismo , Displasia do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/metabolismo
8.
Int J Biol Macromol ; 269(Pt 2): 132216, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729483

RESUMO

Agricultural by-products of sesame are promising bioresources in food processing. This study extracted lignin from the by-products of sesame oil production, namely, the capsules and straw of black and white sesame. Using acid, alkali, and ethanol methods, 12 distinct lignins were obtained to prepare biochar, aiming to investigate both the structural characteristics of lignin-based biochar (LBB) and its ability to remove benzo[a]pyrene (BaP) from sesame oil. The results showed that white sesame straw was the most suitable raw material for preparing biochar. In terms of the preparation method, acid-extracted lignin biochar was more effective in removing BaP than alkaline or ethanol methods. Notably, WS-1LB (white sesame straw acid-extracted lignin biochar) exhibited the highest BaP adsorption efficiency (91.44 %) and the maximum specific surface area (1065.8187 m2/g), characterized by porous structures. The pseudo 2nd and Freundlich models were found to be the best fit for the adsorption kinetics and isotherms of BaP on LBB, respectively, suggesting that a multilayer adsorption process was dominant. The high adsorption of LBB mainly resulted from pore filling. This study provides an economical and highly efficient biochar adsorbent for the removal of BaP in oil.


Assuntos
Carvão Vegetal , Lignina , Óleo de Gergelim , Lignina/química , Carvão Vegetal/química , Adsorção , Óleo de Gergelim/química , Benzo(a)pireno/química , Cinética
9.
World J Psychiatry ; 14(5): 715-725, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38808090

RESUMO

BACKGROUND: Psychological distress, especially depression, associated with perianal fistulizing Crohn's disease (PFCD) is widespread and refractory. However, there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD. AIM: To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD. METHODS: The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff. Depressive symptoms, life quality, and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9, Inflammatory Bowel Disease Patient Quality of Life Questionnaire (IBDQ), and Inflammatory Bowel Disease (IBD) Fatigue Patient Self-assessment Scale. The basic demographic information, overall disease features, perianal clinical information, and laboratory inflammation indicators were also gathered. Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD. RESULTS: A total of 123 patients with PFCD were involved, and 56.91% were suffering from depression. According to multivariate logistic regression analysis, Perianal Disease Activity Index (PDAI) score [odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.50 to 0.95], IBDQ score (OR = 0.93, 95%CI: 0.88 to 0.97), modified Van Assche index (OR = 1.24, 95%CI: 1.01 to 1.53), and IBD Fatigue score (OR = 1.72, 95%CI: 1.23 to 2.42) were independent risk factors of depression-related prevalence among patients with PFCD (P < 0.05). Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index (ß value = 0.166, 95%CI: 0.02 to 0.31) and decreasing IBDQ score (ß value = -0.116, 95%CI: -0.14 to -0.09) were independently associated with the severity of depression (P < 0.05). CONCLUSION: Depressive symptoms in PFCD patients have significantly high prevalence. PDAI score, modified Van Assche index, quality of life, and fatigue severity were the main independent risk factors.

10.
J Fr Ophtalmol ; 47(7): 104213, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38788251

RESUMO

PURPOSE: To investigate the rate of axial length elongation and high myopia progression in operated eyes before and after posterior scleral reinforcement (PSR) surgery. METHODS: This was a retrospective study. Children with pathological myopia treated with PSR at Beijing Tongren Hospital between May 2013 and May 2020 were recruited into the PSR surgery group. Children matched for age and myopia were recruited into the control group. All children underwent comprehensive ophthalmologic examinations. The presurgical and postsurgical rates of axial length elongation and myopic (spherical equivalent) progression were calculated. RESULTS: A total of 35 PSR patients were included in the study. The mean age was 6.5±3.0 years (range 2 to 14 years). Mean follow-up was 544 days (range 216 to 1657 days). The rate of axial length elongation was significantly less after posterior scleral reinforcement surgery (0.505±0.048mm per year prior to surgery; 0.382±0.045mm per year after surgery, P<0.001). The rate of myopic progression decreased after posterior scleral reinforcement surgery (1.162±0.118 D per year prior to surgery; 0.153±0.437 D per year after surgery, P=0.0239). There was no statistically significant difference in axial length elongation or myopic progression between pre-inclusion and post-inclusion in the control group. Moreover, the children's best-corrected visual acuity was significantly improved after posterior scleral reinforcement surgery (P<0.001). CONCLUSION: Posterior scleral reinforcement surgery effectively decreased the rate of high myopic progression and axial length elongation in children.

11.
Adv Mater ; 36(28): e2404296, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38685574

RESUMO

Fluorescence imaging-guided photodynamic therapy (FIG-PDT) holds promise for cancer treatment, yet challenges persist in poor imaging quality, phototoxicity, and insufficient anti-tumor effect. Herein, a novel nanoplatform, LipoHPM, designed to address these challenges, is reported. This approach employs an acid-sensitive amine linker to connect a biotin-modified hydrophilic polymer (BiotinPEG) with a new hydrophobic photosensitizer (MBA), forming OFF-state BiotinPEG-MBA (PM) micelles via an aggregation-caused quenching (ACQ) effect. These micelles are then co-loaded with the tumor penetration enhancer hydralazine (HDZ) into pH-sensitive liposomes (LipoHPM). Leveraging the ACQ effect, LipoHPM is silent in both fluorescence and reactive oxygen species (ROS) generation during blood circulation but restores both properties upon disassembly. Following intravenous injection in tumor-bearing mice, LipoHPM actively targets tumor cells overexpressing biotin-receptors, contributing to enhanced tumor accumulation. Upon cellular internalization, LipoHPM disassembles within lysosomes, releasing HDZ to enhance tumor penetration and inhibit tumor metastasis. Concurrently, the micelles activate fluorescence for tumor imaging and boost the production of both type-I and type-II ROS for tumor eradication. Therefore, the smart LipoHPM synergistically integrates near-infrared emission, activatable tumor imaging, robust ROS generation, efficient anti-tumor and anti-metastasis activity, successfully overcoming limitations of conventional photosensitizers and establishing itself as a promising nanoplatform for potent FIG-PDT applications.


Assuntos
Micelas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Animais , Camundongos , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Linhagem Celular Tumoral , Imagem Óptica , Lipossomos/química , Neoplasias/tratamento farmacológico , Neoplasias/diagnóstico por imagem , Raios Infravermelhos , Nanopartículas/química , Polímeros/química , Biotina/química
12.
Biochem Biophys Res Commun ; 710: 149885, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38588612

RESUMO

Oxidative stress is a key factor in the disruption of cartilage homeostasis during the development of osteoarthritis (OA). Organic selenium (Se)-containing compounds such as diselenides have excellent antioxidant activity and may prevent related diseases. We aimed to examine the benefits of the synthetic small molecule diphenyl diselenide (DPDSe) in OA models in vitro and in vivo. Our findings showed that DPDSe could maintain extracellular matrix (ECM) homeostasis and inhibit reactive oxygen species (ROS) production in IL-1ß-treated chondrocytes. In a destabilization of the medial meniscus (DMM)-induced OA mouse model, intra-articular administration of DPDSe alleviated joint degeneration, as evidenced by a decrease in the OARSI score and the restoration of collagen II (COL2) and MMP-13 expression in cartilage tissues. We confirmed that DDS activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in IL-1ß-treated chondrocytes, and its chondroprotective effects were significantly counteracted when Nrf2 signaling was blocked by the inhibitor ML385 or by siRNA-mediated Nrf2 knockdown. The relatively strong performance of DPDSe makes it an ideal candidate for further trials as a disease-modifying OA drug (DMOAD).


Assuntos
Derivados de Benzeno , Compostos Organosselênicos , Osteoartrite , Camundongos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Transdução de Sinais , Compostos Organosselênicos/farmacologia , Compostos Organosselênicos/uso terapêutico , Condrócitos/metabolismo , Interleucina-1beta/metabolismo
13.
World J Psychiatry ; 14(3): 370-379, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38617978

RESUMO

BACKGROUND: Dexmedetomidine and propofol are two sedatives used for long-term sedation. It remains unclear whether dexmedetomidine provides superior cerebral protection for patients undergoing long-term mechanical ventilation. AIM: To compare the neuroprotective effects of dexmedetomidine and propofol for sedation during prolonged mechanical ventilation in patients without brain injury. METHODS: Patients who underwent mechanical ventilation for > 72 h were randomly assigned to receive sedation with dexmedetomidine or propofol. The Richmond Agitation and Sedation Scale (RASS) was used to evaluate sedation effects, with a target range of -3 to 0. The primary outcomes were serum levels of S100-ß and neuron-specific enolase (NSE) every 24 h. The secondary outcomes were remifentanil dosage, the proportion of patients requiring rescue sedation, and the time and frequency of RASS scores within the target range. RESULTS: A total of 52 and 63 patients were allocated to the dexmedetomidine group and propofol group, respectively. Baseline data were comparable between groups. No significant differences were identified between groups within the median duration of study drug infusion [52.0 (IQR: 36.0-73.5) h vs 53.0 (IQR: 37.0-72.0) h, P = 0.958], the median dose of remifentanil [4.5 (IQR: 4.0-5.0) µg/kg/h vs 4.6 (IQR: 4.0-5.0) µg/kg/h, P = 0.395], the median percentage of time in the target RASS range without rescue sedation [85.6% (IQR: 65.8%-96.6%) vs 86.7% (IQR: 72.3%-95.3), P = 0.592], and the median frequency within the target RASS range without rescue sedation [72.2% (60.8%-91.7%) vs 73.3% (60.0%-100.0%), P = 0.880]. The proportion of patients in the dexmedetomidine group who required rescue sedation was higher than in the propofol group with statistical significance (69.2% vs 50.8%, P = 0.045). Serum S100-ß and NSE levels in the propofol group were higher than in the dexmedetomidine group with statistical significance during the first six and five days of mechanical ventilation, respectively (all P < 0.05). CONCLUSION: Dexmedetomidine demonstrated stronger protective effects on the brain compared to propofol for long-term mechanical ventilation in patients without brain injury.

14.
Int Immunopharmacol ; 132: 111935, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599096

RESUMO

Finding novel therapeutic modalities, improving drug delivery efficiency and targeting, and reducing the immune escape of tumor cells are currently hot topics in the field of tumor therapy. Bacterial therapeutics have proven highly effective in preventing tumor spread and recurrence, used alone or in combination with traditional therapies. In recent years, a growing number of researchers have significantly improved the targeting and penetration of bacteria by using genetic engineering technology, which has received widespread attention in the field of tumor therapy. In this paper, we provide an overview and assessment of the advancements made in the field of tumor therapy using genetically engineered bacteria. We cover three major aspects: the development of engineered bacteria, their integration with other therapeutic techniques, and the current state of clinical trials. Lastly, we discuss the limitations and challenges that are currently being faced in the utilization of engineered bacteria for tumor therapy.


Assuntos
Bactérias , Engenharia Genética , Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Animais , Bactérias/genética , Imunoterapia/métodos , Sistemas de Liberação de Medicamentos
16.
Angew Chem Int Ed Engl ; 63(22): e202403539, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38556813

RESUMO

The design and orderly layered co-immobilization of multiple enzymes on resin particles remain challenging. In this study, the SpyTag/SpyCatcher binding pair was fused to the N-terminus of an alcohol dehydrogenase (ADH) and an aldo-keto reductase (AKR), respectively. A non-canonical amino acid (ncAA), p-azido-L-phenylalanine (p-AzF), as the anchor for covalent bonding enzymes, was genetically inserted into preselected sites in the AKR and ADH. Employing the two bioorthogonal counterparts of SpyTag/SpyCatcher and azide-alkyne cycloaddition for the immobilization of AKR and ADH enabled sequential dual-enzyme coating on porous microspheres. The ordered dual-enzyme reactor was subsequently used to synthesize (S)-1-(2-chlorophenyl)ethanol asymmetrically from the corresponding prochiral ketone, enabling the in situ regeneration of NADPH. The reactor exhibited a high catalytic conversion of 74 % and good reproducibility, retaining 80 % of its initial activity after six cycles. The product had 99.9 % ee, which that was maintained in each cycle. Additionally, the double-layer immobilization method significantly increased the enzyme loading capacity, which was approximately 1.7 times greater than that of traditional single-layer immobilization. More importantly, it simultaneously enabled both the purification and immobilization of multiple enzymes on carriers, thus providing a convenient approach to facilitate cascade biocatalysis.


Assuntos
Álcool Desidrogenase , Biocatálise , Enzimas Imobilizadas , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Álcool Desidrogenase/metabolismo , Álcool Desidrogenase/química , Álcool Desidrogenase/genética , Engenharia de Proteínas , Aldo-Ceto Redutases/metabolismo , Aldo-Ceto Redutases/química , Aldo-Ceto Redutases/genética , Fenilalanina/química , Fenilalanina/metabolismo , Fenilalanina/análogos & derivados , Azidas/química
17.
Food Funct ; 15(7): 3552-3565, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38465899

RESUMO

Osteoarthritis is the most prevalent degenerative joint disease reported worldwide. Conventional treatment strategies mainly focus on medication and involve surgical joint replacement. The use of these therapies is limited by gastrointestinal complications and the lifespan of joint prostheses. Hence, safe and efficacious drugs are urgently needed to impede the osteoarthritis progression. Urolithin B, a metabolite of ellagic acid in the gut, exhibits anti-inflammatory and antioxidant properties; however, its role in osteoarthritis remains unclear. In this study, we demonstrated that urolithin B efficiently inhibits the inflammatory factor-induced production of matrix metalloproteinases (MMP3 and MMP13) in vitro and upregulates the expression of type II collagen and aggrecan. Urolithin B alleviates cartilage erosion and osteophyte formation induced by anterior cruciate ligament transections. Moreover, urolithin B inhibits the activation of the NF-κB pathway by reducing the phosphorylation of Iκb-α and the nuclear translocation of P65. In summary, urolithin B significantly inhibits inflammation and alleviates osteoarthritis. Hence, urolithin B can be considered a potential agent suitable for the effective treatment of osteoarthritis in the future.


Assuntos
Cumarínicos , Osteoartrite , Transdução de Sinais , Humanos , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Condrócitos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Cartilagem/metabolismo , Interleucina-1beta/metabolismo
18.
J Environ Manage ; 356: 120591, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38490008

RESUMO

Research on the potential for chemical energy recovery and the optimization of recovery pathways in different regions of China is still lacking. This study aimed to address this gap by evaluating the potential and optimize the utilization pathways for chemical energy recovery in various regions of China for achieving sustainable wastewater treatment. The results showed that the eastern and northeastern regions of China exhibited higher chemical energy levels under the existing operating conditions. Key factors affecting chemical energy recovery included chemical oxygen demand removal (ΔCOD), treatment scale, and specific energy consumption (µ) of wastewater treatment plants (WWTPs). Furthermore, the average improvement in the chemical energy recovery rate with an optimized utilization pathway was approximately 40% in the WWTPs. The use of the net-zero energy consumption (NZE) model proved effective in improving the chemical energy recovery potential, with an average reduction of greenhouse gas (GHG) emissions reaching next to 95% in the investigated WWTPs.


Assuntos
Poluentes Ambientais , Purificação da Água , Águas Residuárias , Eliminação de Resíduos Líquidos/métodos , Purificação da Água/métodos , China
19.
Nat Prod Res ; : 1-5, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38516729

RESUMO

Bufo gargarizans Cantor (B. gargarizans) is the most widely distributed and abundant species of toad in China. Bufadienolides and indole alkaloids have cardiotonic and anti-tumor activities and are important pharmacological components of B. bufo gargarizans. In this experiment, a novel compound (1) and two known compounds (2 and 3) were isolated and identified from the dry skin of B. bufo gargarizans, both of which are bufadienolides. Various column chromatography methods were used to separate and purify the extract from the dried skin of B. bufo gargarizans. Accurate molecular weights were measured by HR-ESI-MS, and the chemical structure of the compounds was determined by NMR spectrometers. The structures were named as (2ß,5ß,16α)-2,5,16-trihydroxide bufa-14,20,22 dienolide (1), gamabufotalin (2) and desacetylbufotalin (3). In vitro cytotoxic activity assay indicated that compound 1 showed a moderate cytotoxicity against A549 cells with IC50 value of 12.65 µM.

20.
Int J Biol Macromol ; 264(Pt 1): 130612, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38447845

RESUMO

Effective photolytic regeneration of the NAD(P)H cofactor in enzymatic reductions is an important and elusive goal in biocatalysis. It can, in principle, be achieved using a near-infrared light (NIR) driven artificial photosynthesis system employing H2O as the sacrificial reductant. To this end we utilized TiO2/reduced graphene quantum dots (r-GQDs), combined with a novel rhodium electron mediator, to continuously supply NADPH in situ for aldo-keto reductase (AKR) mediated asymmetric reductions under NIR irradiation. This upconversion system, in which the Ti-O-C bonds formed between r-GQDs and TiO2 enabled efficient interfacial charge transfer, was able to regenerate NADPH efficiently in 64 % yield in 105 min. Based on this, the pharmaceutical intermediate (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol was obtained, in 84 % yield and 99.98 % ee, by reduction of the corresponding ketone. The photo-enzymatic system is recyclable with a polymeric electron mediator, which maintained 66 % of its original catalytic efficiency and excellent enantioselectivity (99.9 % ee) after 6 cycles.


Assuntos
Raios Infravermelhos , NAD , NADP , Aldo-Ceto Redutases , NAD/metabolismo , Fotossíntese
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