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1.
Bioresour Technol ; 413: 131512, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39307473

RESUMO

The implementation of environmentally friendly and sustainable remediation strategies positively impacts solid waste management. In this study, the Kocuria marina H-2 and Pseudomonas putida B6-2 co-culture system demonstrated enhanced naphthalene biodegradation efficiency compared to single-strain cultures. Under optimal conditions of 35 °C, 200 rpm/min, and a 1:1 ratio of the co-culture system, the naphthalene biodegradation potential was further increased. Notably, the addition of both ethylenediamine-pretreated lignin and p-hydroxybenzoic acid significantly elevated naphthalene degradation rates to 68.5 %. In addition, the oil-liquid surface tension decreased, while cell surface hydrophobicity and colony-forming units increased with the addition of lignin-derived compounds. The modification of naphthalene bioavailability by ethylenediamine-pretreated lignin would accelerate the uptake and transport of hydrocarbons via ABC transporters and flagellar assembly. Importantly, genes related to bacterial chemotaxis and fatty acid biosynthesis were upregulated during the co-metabolism of naphthalene and p-hydroxybenzoic acid, further enhancing naphthalene bioconversion.

2.
Biomater Sci ; 12(19): 5076-5090, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39219371

RESUMO

Metabolic disorders of cancer cells create opportunities for metabolic interventions aimed at selectively eliminating cancer cells. Nevertheless, achieving this goal is challenging due to cellular plasticity and metabolic heterogeneity of cancer cells. This study presents a dual-drug-loaded, macrophage membrane-coated polymeric nanovesicle designed to reprogram cancer metabolism with high specificity through integrated extracellular and intracellular interventions. This nanoformulation can target cancer cells and largely reduce their glucose intake, while the fate of intracellular glucose internalized otherwise is redirected at the specially introduced oxidation reaction instead of inherent cancer glycolysis. Meanwhile, it inhibits cellular citrate intake, further reinforcing metabolic intervention. Furthermore, the nanoformulation causes not only H2O2 production, but also NADPH down-regulation, intensifying redox damage to cancer cells. Consequently, this nanoformulation displays highly selective toxicity to cancer cells and minimal harm to normal cells mainly due to metabolic vulnerability of the former. Once administered into tumor-bearing mice, this nanoformulation is found to induce the transformation of pro-tumor tumor associated macrophages into the tumor-suppressive phenotype and completely inhibit tumor growth with favourable biosafety.


Assuntos
Nanopartículas , Polímeros , Animais , Camundongos , Humanos , Polímeros/química , Polímeros/farmacologia , Polímeros/administração & dosagem , Nanopartículas/química , Nanopartículas/administração & dosagem , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Glucose/metabolismo , Células RAW 264.7 , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Portadores de Fármacos/química , Proliferação de Células/efeitos dos fármacos , Reprogramação Metabólica
3.
Artigo em Inglês | MEDLINE | ID: mdl-39303011

RESUMO

The nanoscale multidrug codelivery system for synergistic therapy is an effective strategy for tumor treatment. However, the low drug delivery efficiency and poor therapeutic effects limit its application. Here, based on the coordination effect of Artemisinin (Art), quercetin (Qc), and Fe3+, we had constructed a safe and efficient carrier-free hyaluronic acid (HA)-modified Art-Fe-Qc nanoparticles (AFQ@HA NPs) for enhanced chemotherapy/photothermal therapy (PTT)-chemodynamic therapy (CDT) synergistic therapy, which achieved an ultrahigh drug loading efficiency and a multifunction anticancer strategy. The results showed that high drug loading was achieved based on drug coordination self-assembly, with Art and Qc contents of 38.6 and 42.7%, respectively. At the same time, based on the Qc-Fe coordination molecular network, the system had excellent photothermal conversion performance with an efficiency of 57.3% and could effectively inhibit the expression of HSP70, achieving enhanced PTT. Further, under the stimulation of excessive H2O2 and glutathione (GSH) in the tumor microenvironment, the AFQ@HA NPs were continuously degraded, while releasing Art and Fe3+/Fe2+ to achieve iron ion-enhanced CDT. The results of in vitro and in vivo experiments showed that AFQ@HA NPs could achieve chemotherapy-PTT-CDT synergistic therapy in response to tumor microenvironment by passively targeting and actively targeting tumor cells with CD44, demonstrating its excellent targeted antitumor effects.

4.
Ying Yong Sheng Tai Xue Bao ; 35(6): 1509-1517, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-39235008

RESUMO

We established a mixed-effects model incorporating climatic factors for the base diameter and length of the primary branches of Larix kaempferi using stepwise regression, based on climatic data from a total of 40 standard plots located in Xiaolongshan, Gansu Province, Changlinggang Forest Farm in Jianshi County, Hubei Province, and Dagujia Forest Farm in Qingyuan County, Liaoning Province, as well as the data from 120 L. kaempferi sample trees. Additionally, we created prediction charts for the fixed effects portion of the optimal mixed model to determine the relationship between climatic factors and base diameter and branch length, to explore the differential response of L. kaempferi branches to climatic variables. The results showed that the base diameter mixing model with annual mean temperature and water vapor deficit and the branch length mixing model with annual mean temperature had the best fitting effect, with R2 of 0.6152 and 0.6823, respectively. Based on the fixed effects prediction chart of the mixed model, the overall basal diameter showed an increasing trend with the increases of relative branch depth. The average basal diameter size was in an order of young-aged plantation

Assuntos
Clima , Larix , Larix/crescimento & desenvolvimento , China , Temperatura , Caules de Planta/crescimento & desenvolvimento , Modelos Teóricos , Ecossistema
5.
Ying Yong Sheng Tai Xue Bao ; 35(6): 1608-1614, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-39235019

RESUMO

As a kind of tonic Chinese medicine with dual use in medicine and food, there is a large market demanding for Codonopsis pilosula. Taking one-year-old C. pilosula seedlings as materials, we conducted a field experiment to examine the effect of compound fertilizer (750 kg·hm-2), organic fertilizer (15 t·hm-2) and Streptomyces pactum Act12 agent (9 t·hm-2 Act12+10 t·hm-2 organic fertilizer) treatments on root morphology, secondary metabolite content and expression level of lobetyolin metabolic pathway gene of C. pilosula, to clarify the effects of three fertilizers on the root morphology and medicinal quality. Compared to the control (10 t·hm-2 organic fertilizer, conventional fertilization), three fertilization treatments could promote root growth and formation. All fertilization treatments promoted the accumulation of C. pilosula polysaccharides and secondary metabolites. Act12 agent significantly increased the content of lobetyolin, atractylenolideIII, and 5-hydroxymethylfurfural. The qRT-PCR analysis indicated that three fertilization treatments increased the expression level of lobetyolin metabolic pathway genes, with Act12 agent treatment showing the most significant effect. Pearson correlation analysis demonstrated that the expression level of CpHCT and CpFAD genes was significantly positively correlated with atractylenolide III content. In conclusion, three fertilization treatments could effectively improve the yield and quality of C. pilosula. Among the three treatments, Act12 agent performed better than that of compound fertilizer and organic fertilizer, which was an effective measure to increase the yield and quality of C. pilosula.


Assuntos
Codonopsis , Fertilizantes , Raízes de Plantas , Streptomyces , Codonopsis/crescimento & desenvolvimento , Codonopsis/metabolismo , Streptomyces/crescimento & desenvolvimento , Streptomyces/metabolismo , Streptomyces/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plantas Medicinais/crescimento & desenvolvimento , Plantas Medicinais/metabolismo , Plantas Medicinais/química
6.
Public Health ; 236: 193-203, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39265377

RESUMO

OBJECTIVES: Bladder cancer is a common malignancy worldwide, with substantial morbidity and mortality. This study aimed to assess the global, regional, and national burden of bladder cancer from 1990 to 2019 using data from the Global Burden of Disease (GBD) 2019 study and to analyze the trends using an age-period-cohort (APC) model. STUDY DESIGN: In this cross-sectional study, secondary analyses were conducted to assess the burden of bladder cancer using data from GBD 2019. METHODS: Bladder cancer prevalence, incidence, mortality, disability-adjusted life years (DALYs), and their age-standardized rates (ASRs) were obtained from the GBD 2019 study. The estimated annual percentage changes (EAPCs) were calculated to quantify the trends in ASRs. An APC analysis was performed to distinguish the effects of age, period, and cohort on the observed temporal trends. RESULTS: The global prevalence of bladder cancer increased substantially from 1990 to 2019, reaching 2,869,046.4 cases (95% UI: 2,614,200.3-3,114,474.4) in 2019. The age-standardized prevalence rate rose from 20.9 per 100,000 population in 1990 to 37.1 per 100,000 population in 2019, with an EAPC of 1.97 (95% CI: 1.93-2.01). The global burden of bladder cancer, as measured by DALYs, increased from 48.0 per 100,000 population in 1990 to 56.8 per 100,000 population in 2019, with an EAPC of 0.47 (95% CI: 0.4-0.53), demonstrating the growing impact of this disease on population health. CONCLUSIONS: This study demonstrates a significant increase in prevalence, incidence, mortality, and DALYs, with substantial variations across sociodemographic index (SDI) quintiles and GBD regions. The findings emphasize the need for concerted efforts at the global, regional, and national levels to reduce the burden of bladder cancer through primary prevention, early detection, and improved access to treatment services.

7.
Angew Chem Int Ed Engl ; : e202413428, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39254504

RESUMO

Different from the reported work focusing on the construction of single P- or C-stereocenter via hydrophosphinylation of unsaturated carbon bonds, the highly diastereo- and enantioselective hydrophosphinylation reaction of allenes, conjugated enynes and 1,3-dienes is achieved via a designed Pd/Co dual catalysis and newly modified masked phosphinylating reagent. A series of allyl motifs bearing both a tertiary C- and P-stereocenter are prepared in generally good yields, >20:1 dr, >20:1 rr and 99% ee. The unprecedented diastereo- and enantioselective hydrophosphinylation of 1,3-enynes is established to generate skeletons containing both a P-stereocenter and a nonadjacent chiral axis. The first stereodivergent hydrophosphinylation reaction is also developed to achieve all four P-containing stereoisomers. The present protocol features the use of only 3-minutes reaction time and 0.1% catalyst, and with the observation of up to 730 TON. A set of mechanistic studies reveal the necessity and roles of two metal catalysts and corroborate the designed synergistic process.

8.
Chin J Integr Med ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225883

RESUMO

OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. ß-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS: YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. ß-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.

9.
Asia Pac J Clin Nutr ; 33(4): 539-544, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39209363

RESUMO

BACKGROUND AND OBJECTIVES: Women are more prone to iron deficiency (ID) anemia when pregnant. The diagnostic use of mean reticulocyte volume (MRV) in identifying ID anemia during pregnancy has not been thoroughly investigated. The objective of this study is to evaluate the effectiveness of MRV in diagnosing ID in pregnant women. METHODS AND STUDY DESIGN: Firstly, MRV of 20 healthy female volunteers (healthy group) was measured on specific days for one month. Subsequently, clinical data from 724 pregnant women were thoroughly examined. These women were divided into two groups: 282 with ID (research group) and 442 without ID (control group). Parameters such as MRV, reticulocyte hemoglobin equivalent (RHE), red blood cell volume distribution width-standard deviation (RDW-SD), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), hematocrit (HCT), reticulocyte count (RET), MRV/MCV ratio, and serum ferritin (SF) were analyzed and compared. RESULTS: MRV remained consistent over a period of one month for 20 healthy individuals. In addition, there were significant differences in MRV, RHE, RDW-SD, MCV, MCH, MCHC, HCT, RET, and MRV/MCV between the research group and control group. The receiver operating characteristic (ROC) analysis showed that the areas under the curve (AUCs) for these measures were as follow: 0.840, 0.837, 0.676, 0.654, 0.639, 0.602, 0.571, 0.550, and 0.816, respectively. Ultimately, there was a substantial disparity in MRV prior to and following therapy with oral iron treatments. CONCLUSIONS: In healthy women, MRV remains stable and is a reliable ID marker, which can be used to assess oral iron treatment effectiveness during pregnancy.


Assuntos
Anemia Ferropriva , Reticulócitos , Humanos , Feminino , Gravidez , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/sangue , Adulto , Índices de Eritrócitos , Contagem de Reticulócitos , Adulto Jovem , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/diagnóstico
10.
Ren Fail ; 46(2): 2387205, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39120130

RESUMO

BACKGROUND: To compare the impact of tunneled cuffed catheters (TCCs) and arteriovenous fistulas (AVFs) on outcomes in elderly hemodialysis (HD) patients. METHODS: A retrospective matched cohort study was performed. Propensity score matching (PSM) was applied to balance the baseline conditions, and we compared all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCEs), hospitalization, and infection rates between AVF and TCC patients ≥70 years old. Cox survival analysis was used to analyze the risk factors for death. RESULTS: There were 2119 patients from our center in the Chinese National Renal Data System (CNRDS) between 1 January 2010 and 10 October 2023. Among these patients, 77 TCC patients were matched with 77 AVF patients. There was no significant difference in all-cause mortality between the TCC and AVF groups (30.1/100 vs. 33.3/100 patient-years, p = 0.124). Among the propensity score-matched cohorts, no significant differences in Kaplan-Meier curves were observed between the two groups (log-rank p = 0.242). The TCC group had higher rates of MACCEs, hospitalization, and infection than the AVF group (33.7/100 vs. 29.5/100 patient-years, 101.2/100 vs. 79.5/100 patient-years, and 30.1/100 vs. 14.1/100 patient-years, respectively). Multivariate analysis showed that high Charlson comorbidity index (CCI) score was a risk factor for death. CONCLUSIONS: There was no significant difference in all-cause mortality between elderly HD patients receiving TCCs and AVFs. Compared with those with a TCC, elderly HD patients with an AVF have a lower risk of MACCEs, hospitalization, and infection.


Assuntos
Derivação Arteriovenosa Cirúrgica , Falência Renal Crônica , Pontuação de Propensão , Diálise Renal , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Fatores de Risco , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Idoso de 80 Anos ou mais , Hospitalização/estatística & dados numéricos , China/epidemiologia , Prognóstico , Estimativa de Kaplan-Meier
11.
BMC Gastroenterol ; 24(1): 286, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187774

RESUMO

BACKGROUND: To investigate the effect of different working periods on missed diagnoses in patients with colorectal polyps in colonoscopy. METHODS: We conducted a retrospective analysis of patients who were diagnosed with colorectal polyps during colonoscopy in an outpatient department between July and December 2022. These patients were subsequently hospitalized for resection during this period. Patients with missed diagnoses were those who had newly discovered polyps in a second colonoscopy. The working periods were categorized as work, near the end of work, and delayed work, respectively, in the morning and afternoon. RESULTS: A total of 482 patients were included, and the miss rate of diagnosis was 48.1% (232/482), mainly in the transverse colon (25%), and the ascending colon (23%). Patient age was a risk factor for the miss rate of diagnosis (OR = 1.025, 95%CI: 1.009-1.042, P = 0.003) and was also associated with the number of polyps detected for the first colonoscopy (χ2 = 18.196, P = 0.001). The different working periods had no statistical effect on the missed rate of diagnosis (χ2 = 1.998, P = 0.849). However, there was an increasing trend in miss rates towards the end of work and delayed work periods, both in the morning and afternoon. The highest miss rate (60.0%) was observed during delayed work in the afternoon. Additionally, poor bowel preparation was significantly more common during delayed work in the afternoon. CONCLUSIONS: The increasing trend in miss rates towards the end of work and delayed work periods deserves clinical attention. Endoscopists cannot always stay in good condition under heavy workloads.


Assuntos
Pólipos do Colo , Colonoscopia , Diagnóstico Ausente , Humanos , Colonoscopia/estatística & dados numéricos , Estudos Retrospectivos , Masculino , Diagnóstico Ausente/estatística & dados numéricos , Feminino , Pólipos do Colo/diagnóstico , Pólipos do Colo/patologia , Pessoa de Meia-Idade , Idoso , Adulto , Fatores de Tempo , Fatores de Risco , Fatores Etários , Erros de Diagnóstico/estatística & dados numéricos
12.
Org Lett ; 26(35): 7468-7473, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39189837

RESUMO

The base-mediated allylic defluorinative functionalization of ß-CF2H-1,3-enynes with nucleophiles is described, affording terminal monofluoroalkenes bearing an alkynyl group in synthetically useful yields and Z/E selectivities. Importantly, the resultant Z/E mixture could be separated by flash chromatography in all cases; thus, stereoisomerically pure monofluoroenynes were obtained. Postsynthetic modifications of the synthesized monofluoroenynes were also accomplished to access diverse molecular structures. Computational studies disclosed the origin of the diastereoselectivity.

14.
Infect Dis Poverty ; 13(1): 54, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38982550

RESUMO

BACKGROUND: Rickettsia and related diseases have been identified as significant global public health threats. This study involved comprehensive field and systematic investigations of various rickettsial organisms in Yunnan Province. METHODS: Between May 18, 2011 and November 23, 2020, field investigations were conducted across 42 counties in Yunnan Province, China, encompassing small mammals, livestock, and ticks. Preliminary screenings for Rickettsiales involved amplifying the 16S rRNA genes, along with additional genus- or species-specific genes, which were subsequently confirmed through sequencing results. Sequence comparisons were carried out using the Basic Local Alignment Search Tool (BLAST). Phylogenetic relationships were analyzed using the default parameters in the Molecular Evolutionary Genetics Analysis (MEGA) program. The chi-squared test was used to assess the diversities and component ratios of rickettsial agents across various parameters. RESULTS: A total of 7964 samples were collected from small mammals, livestock, and ticks through Yunnan Province and submitted for screening for rickettsial organisms. Sixteen rickettsial species from the genera Rickettsia, Anaplasma, Ehrlichia, Neoehrlichia, and Wolbachia were detected, with an overall prevalence of 14.72%. Among these, 11 species were identified as pathogens or potential pathogens to humans and livestock. Specifically, 10 rickettsial organisms were widely found in 42.11% (24 out of 57) of small mammal species. High prevalence was observed in Dremomys samples at 5.60%, in samples from regions with latitudes above 4000 m or alpine meadows, and in those obtained from Yuanmou County. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis were broadly infecting multiple genera of animal hosts. In contrast, the small mammal genera Neodon, Dremomys, Ochotona, Anourosorex, and Mus were carrying individually specific rickettsial agents, indicating host tropism. There were 13 rickettsial species detected in 57.14% (8 out of 14) of tick species, with the highest prevalence (37.07%) observed in the genus Rhipicephalus. Eight rickettsial species were identified in 2375 livestock samples. Notably, six new Rickettsiales variants/strains were discovered, and Candidatus Rickettsia longicornii was unambiguously identified. CONCLUSIONS: This large-scale survey provided further insight into the high genetic diversity and overall prevalence of emerging Rickettsiales within endemic hotspots in Yunnan Province. The potential threats posed by these emerging tick-borne Rickettsiales to public health warrant attention, underscoring the need for effective strategies to guide the prevention and control of emerging zoonotic diseases in China.


Assuntos
Variação Genética , Filogenia , Rickettsiales , Carrapatos , China/epidemiologia , Animais , Prevalência , Rickettsiales/genética , Rickettsiales/isolamento & purificação , Rickettsiales/classificação , Carrapatos/microbiologia , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/análise , Gado/microbiologia , Infecções por Rickettsia/epidemiologia , Infecções por Rickettsia/microbiologia , Infecções por Rickettsia/veterinária , Rickettsia/isolamento & purificação , Rickettsia/genética , Rickettsia/classificação , Mamíferos/microbiologia , Humanos
15.
Genes Dis ; 11(5): 101042, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38966041

RESUMO

A long noncoding RNA (lncRNA) is longer than 200 bp. It regulates various biological processes mainly by interacting with DNA, RNA, or protein in multiple kinds of biological processes. Adenosine monophosphate-activated protein kinase (AMPK) is activated during nutrient starvation, especially glucose starvation and oxygen deficiency (hypoxia), and exposure to toxins that inhibit mitochondrial respiratory chain complex function. AMPK is an energy switch in organisms that controls cell growth and multiple cellular processes, including lipid and glucose metabolism, thereby maintaining intracellular energy homeostasis by activating catabolism and inhibiting anabolism. The AMPK signalling pathway consists of AMPK and its upstream and downstream targets. AMPK upstream targets include proteins such as the transforming growth factor ß-activated kinase 1 (TAK1), liver kinase B1 (LKB1), and calcium/calmodulin-dependent protein kinase ß (CaMKKß), and its downstream targets include proteins such as the mechanistic/mammalian target of rapamycin (mTOR) complex 1 (mTORC1), hepatocyte nuclear factor 4α (HNF4α), and silencing information regulatory 1 (SIRT1). In general, proteins function relatively independently and cooperate. In this article, a review of the currently known lncRNAs involved in the AMPK signalling pathway is presented and insights into the regulatory mechanisms involved in human ageing and age-related diseases are provided.

16.
Asian J Androl ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38978290

RESUMO

ABSTRACT: Compounds isolated from Epimedium include the total flavonoids of Epimedium, icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium, its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.

17.
Metabolism ; 160: 155980, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39053691

RESUMO

BACKGROUND: The effect of coronavirus disease 2019 (COVID-19) on adrenal endocrine metabolism in critically ill patients remains unclear. This study aimed to investigate the alterations in adrenal steroidogenic activity, elucidate underlying mechanisms, provide in situ histopathological evidence, and examine the clinical implications. METHODS: The comparative analyses of the adrenal cortices from 24 patients with fatal COVID-19 and 20 matched controls were performed, excluding patients previously treated with glucocorticoids. SARS-CoV-2 and its receptors were identified and pathological alterations were examined. Furthermore, histological examinations, immunohistochemical staining and ultrastructural analyses were performed to assess corticosteroid biosynthesis. The zona glomerulosa (ZG) and zona fasciculata (ZF) were then dissected for proteomic analyses. The biological processes that affected steroidogenesis were analyzed by integrating histological, proteomic, and clinical data. Finally, the immunoreactivity and responsive genes of mineralocorticoid and glucocorticoid receptors in essential tissues were quantitatively measured to evaluate corticosteroid responsiveness. FINDINGS: The demographic characteristics of COVID-19 patients were comparable with those of controls. SARS-CoV-2-like particles were identified in the adrenocortical cells of three patients; however, these particles did not affect cellular morphology or steroid synthesis compared with SARS-CoV-2-negative specimens. Although the adrenals exhibited focal necrosis, vacuolization, microthrombi, and inflammation, widespread degeneration was not evident. Notably, corticosteroid biosynthesis was significantly enhanced in both the ZG and ZF of COVID-19 patients. The increase in the inflammatory response and cellular differentiation in the adrenal cortices of patients with critical COVID-19 was positively correlated with heightened steroidogenic activity. Additionally, the appearance of more dual-ZG/ZF identity cells in COVID-19 adrenals was in accordance with the increased steroidogenic function. However, activated mineralocorticoid and glucocorticoid receptors and their responsive genes in vital tissues were markedly reduced in patients with critical COVID-19. INTERPRETATION: Critical COVID-19 was characterized by potentiated adrenal steroidogenesis, associated with increased inflammation, enhanced differentiation and elevated dual-ZG/ZF identity cells, alongside suppressed corticosteroid responsiveness. These alterations implied the reduced effectiveness of conventional corticosteroid therapy and underscored the need for evaluation of the adrenal axis and corticosteroid sensitivity.


Assuntos
Corticosteroides , COVID-19 , Estado Terminal , Humanos , COVID-19/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Corticosteroides/uso terapêutico , Corticosteroides/biossíntese , Idoso , SARS-CoV-2 , Zona Fasciculada/metabolismo , Zona Fasciculada/efeitos dos fármacos , Receptores de Glucocorticoides/metabolismo , Adulto , Córtex Suprarrenal/metabolismo , Córtex Suprarrenal/efeitos dos fármacos , Córtex Suprarrenal/patologia , Zona Glomerulosa/metabolismo , Zona Glomerulosa/efeitos dos fármacos , Zona Glomerulosa/patologia , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/efeitos dos fármacos
18.
World J Gastroenterol ; 30(24): 3120-3122, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38983961

RESUMO

Immune checkpoint inhibitors (ICIs) are widely used due to their effectiveness in treating various tumors. Immune-related adverse events (irAEs) are defined as adverse effects resulting from ICI treatment. Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects, such as diarrhea and colitis, which may lead to the discontinuation of ICIs.


Assuntos
Gastrite , Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Gastrite/induzido quimicamente , Gastrite/imunologia , Gastrite/diagnóstico , Gastrite/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neoplasias/imunologia
19.
Biol Sex Differ ; 15(1): 60, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080808

RESUMO

BACKGROUND: Cyp19a1a is a key enzyme in the pathway that converts androgens into estrogen and is regulated by TGF-ß signaling. Smad4 and FoxH1 are downstream effectors of TGF-ß signaling and may play important roles in ovarian development in M. albus. METHODS: We investigated the expression pattern of the Smad4 and FoxH1 using qRT‒PCR and immunofluorescence, then tested the changes of smad4 and foxh1 by qRT‒PCR after ovary incubation with FSH in vitro, and analysed the regulation of cyp19a1a transcription by Smad4 and FoxH1 by dual-luciferase reporter assays. RESULTS: We found that Smad4 encoded a putative protein of 449 amino acids and harbored the three conserved domains typical of this protein family. Smad4 and foxh1 exhibited similar expression patterns during ovarian development and after FSH incubation, with Pearson's coefficients of 0.873 and 0.63-0.81, respectively. Furthermore, Smad4, FoxH1 and Cyp19a1a colocalized in the granulosa cells and theca cells of ovaries during the mid-to-late vitellogenic stage. Smad4 repressed cyp19a1a activity via SBE1 (- 1372/-1364) and SBE2 (- 415/-407) in the cyp19a1a promoter, whereas mutating SBE1 or SBE2 restored cyp19a1a promoter activity. Co-overexpression of Smad4 and FoxH1 significantly reduced cyp19a1a promoter activity. CONCLUSIONS: This study provides new insights into the potential functions of transcription factors Smad4 and FoxH1 in ovarian development and the transcriptional regulation mechanism of cyp19a1a in M. albus, which will reveal Smad4/FoxH1-mediated TGF-ß signaling in reproduction and the regulation of the cyp19a1a. Aromatase, encoded by cyp19a1a, is involved in ovarian development and plays an important role in the quality of eggs, as well the sex ratio, of the teleost fish, M. albus. The research on the transcriptional regulation of cyp19a1a has contributed to the understanding of its role in ovarian development. In previous study, it was shown that FoxH1 inhibits cyp19a1a transcription. In the present study, Smad4 was confirmed as a cyp19a1a transcriptional repressor and Smad4 may also coordinate with FoxH1 to repress cyp19a1a transcription. At present, we provide a new perspective for the transcriptional regulation of cyp19a1a by transcription factors Smad4 and FoxH1 in teleost fish ovary. In the future, the regulatory networks of Smad4 and FoxH1 will be further studied and the gene editing technology will be applied to screen specific regulatory factors of cyp191a1a gene, so as to alter the female cycle and modulate the sex ratio of the eggs production.


Assuntos
Aromatase , Enguias , Fatores de Transcrição Forkhead , Ovário , Regiões Promotoras Genéticas , Proteína Smad4 , Animais , Feminino , Ovário/metabolismo , Aromatase/metabolismo , Aromatase/genética , Proteína Smad4/metabolismo , Proteína Smad4/genética , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Enguias/metabolismo , Proteínas de Peixes/metabolismo , Proteínas de Peixes/genética , Hormônio Foliculoestimulante/metabolismo
20.
J Environ Manage ; 362: 121349, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38833929

RESUMO

The use of Ni-based catalysts is a common method for eliminating tar through catalytic cracking. Carbon deposition is the main cause of deactivation in Ni/ZSM-5 catalysts, with filamentous MWCNTs being the primary form of carbon deposits. This study investigates the formation and evolution of CNTs during the catalytic process of biomass tar to explore the mechanism behind carbon deposition. The effect of the 9Ni/10MWCNTs/81ZSM-5 on toluene reforming was investigated through a vertical furnace. Gases produced by tar catalysis were evaluated through GC analysis. The physicochemical structure, properties and catalytic performance of the catalyst were also tested. TG analysis was used to assess the accumulation and oxidation reactivity of carbon on the catalyst surface. An analysis was conducted on the mechanism of carbon deposition during catalyst deactivation in tar catalysis. The results showed that the 9Ni/91ZSM-5 had a superior toluene conversion of 60.49%, but also experienced rapid and substantial carbon deposition up to 52.69%. Carbon is mainly deposited as curved filaments on both the surface and pore channels of the catalyst. In some cases, tip growth occurs where both carbon deposition and Ni coexist. Furthermore, specific surface area and micropore volume are reduced to varying degrees due to carbon deposition. With the time increased, the amount of carbon deposited on the catalyst surface increased to 62.81%, which gradually approached saturation, and the overall performance of the catalyst was stabilized. This situation causes toluene molecules to detach from the active sites within the catalyst, hindering gas release, which leads to reduced catalytic activity and further carbon deposition. It provides both a basis for the development of new catalysts and an economically feasible solution for practical tar reduction and removal.


Assuntos
Nanotubos de Carbono , Níquel , Catálise , Nanotubos de Carbono/química , Níquel/química , Alcatrões/química , Carbono/química , Tolueno/química , Oxirredução
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