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1.
Cancer Metastasis Rev ; 42(2): 575-587, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37061644

RESUMO

Colorectal cancer (CRC) patients frequently develop liver metastases, which are the major cause of cancer-related mortality. The molecular basis and management of colorectal liver metastases (CRLMs) remain a challenging clinical issue. Recent genomic evidence has demonstrated the liver tropism of CRC and the presence of a stricter evolutionary bottleneck in the liver as a target organ compared to lymph nodes. This bottleneck challenging CRC cells in the liver is organ-specific and requires adaptation not only at the genetic level, but also at the phenotypic level to crosstalk with the hepatic microenvironment. Here, we highlight the emerging evidence on the clonal evolution of CRLM and review recent insights into the molecular mechanisms orchestrating the bidirectional interactions between metastatic CRC cells and the unique liver microenvironment.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/genética , Genômica , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Evolução Molecular , Microambiente Tumoral/genética
2.
Ann Surg Oncol ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879668

RESUMO

INTRODUCTION: Despite the increasing widespread adoption and experience in minimally invasive liver resections (MILR), open conversion occurs not uncommonly even with minor resections and as been reported to be associated with inferior outcomes. We aimed to identify risk factors for and outcomes of open conversion in patients undergoing minor hepatectomies. We also studied the impact of approach (laparoscopic or robotic) on outcomes. METHODS: This is a post-hoc analysis of 20,019 patients who underwent RLR and LLR across 50 international centers between 2004-2020. Risk factors for and perioperative outcomes of open conversion were analysed. Multivariate and propensity score-matched analysis were performed to control for confounding factors. RESULTS: Finally, 10,541 patients undergoing either laparoscopic (LLR; 89.1%) or robotic (RLR; 10.9%) minor liver resections (wedge resections, segmentectomies) were included. Multivariate analysis identified LLR, earlier period of MILR, malignant pathology, cirrhosis, portal hypertension, previous abdominal surgery, larger tumor size, and posterosuperior location as significant independent predictors of open conversion. The most common reason for conversion was technical issues (44.7%), followed by bleeding (27.2%), and oncological reasons (22.3%). After propensity score matching (PSM) of baseline characteristics, patients requiring open conversion had poorer outcomes compared with successful MILR cases as evidenced by longer operative times, more blood loss, higher requirement for perioperative transfusion, longer duration of hospitalization and higher morbidity, reoperation, and 90-day mortality rates. CONCLUSIONS: Multiple risk factors were associated with conversion of MILR even for minor hepatectomies, and open conversion was associated with significantly poorer perioperative outcomes.

3.
Acta Pharmacol Sin ; 45(4): 686-703, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38049578

RESUMO

Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) is the most frequently mutated oncogene in human cancers with mutations predominantly occurring in codon 12. These mutations disrupt the normal function of KRAS by interfering with GTP hydrolysis and nucleotide exchange activity, making it prone to the GTP-bound active state, thus leading to sustained activation of downstream pathways. Despite decades of research, there has been no progress in the KRAS drug discovery until the groundbreaking discovery of covalently targeting the KRASG12C mutation in 2013, which led to revolutionary changes in KRAS-targeted therapy. So far, two small molecule inhibitors sotorasib and adagrasib targeting KRASG12C have received accelerated approval for the treatment of non-small cell lung cancer (NSCLC) harboring KRASG12C mutations. In recent years, rapid progress has been achieved in the KRAS-targeted therapy field, especially the exploration of KRASG12C covalent inhibitors in other KRASG12C-positive malignancies, novel KRAS inhibitors beyond KRASG12C mutation or pan-KRAS inhibitors, and approaches to indirectly targeting KRAS. In this review, we provide a comprehensive overview of the molecular and mutational characteristics of KRAS and summarize the development and current status of covalent inhibitors targeting the KRASG12C mutation. We also discuss emerging promising KRAS-targeted therapeutic strategies, with a focus on mutation-specific and direct pan-KRAS inhibitors and indirect KRAS inhibitors through targeting the RAS activation-associated proteins Src homology-2 domain-containing phosphatase 2 (SHP2) and son of sevenless homolog 1 (SOS1), and shed light on current challenges and opportunities for drug discovery in this field.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia de Alvo Molecular , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Descoberta de Drogas , Guanosina Trifosfato , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/genética , Antineoplásicos/química , Antineoplásicos/uso terapêutico
4.
Pestic Biochem Physiol ; 202: 105967, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879344

RESUMO

Coumarin is a natural product known for its diverse biological activities. While its antifungal properties in agricultural chemistry have been extensively studied, there is limited research on its antibacterial potential. In this study, we developed several novel coumarin derivatives by combining coumarin with pyridinium salt through molecular hybridization and chemical synthesis. Our findings reveal that most of these derivatives exhibit promising antibacterial activity. Among them, derivative A25 has been identified as the most effective compound based on three-dimensional quantitative structure-activity relationships. It demonstrates significant in vitro and in vivo activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicola (Xoc), and Xanthomonas campestris pv. citri (Xac), outperforming the commercially available thiediazole copper. Initial investigations into its mechanism of action suggest that A25 disrupts the cell membranes of Xoc and Xoo, thereby inhibiting bacterial growth. Additionally, A25 enhances the activity of defense enzymes in rice and modulates the expression of proteins related to the pyruvate metabolism pathway. This dual action contributes to rice's resistance against bacterial infestation. We anticipate that this study will serve as a foundation for the development of coumarin-based bactericides.


Assuntos
Antibacterianos , Cumarínicos , Testes de Sensibilidade Microbiana , Oryza , Xanthomonas , Cumarínicos/farmacologia , Cumarínicos/síntese química , Cumarínicos/química , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Xanthomonas/efeitos dos fármacos , Oryza/microbiologia , Compostos de Piridínio/farmacologia , Compostos de Piridínio/química , Compostos de Piridínio/síntese química , Xanthomonas campestris/efeitos dos fármacos , Desenho de Fármacos , Sais/farmacologia , Sais/química , Relação Estrutura-Atividade
5.
J Proteome Res ; 22(4): 1080-1091, 2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-36511424

RESUMO

Investigating the functions of the proteins with no or less functional annotations is an important goal of the HPP (Human Proteome Project) Grand Project. In this study, we investigated the function of such a protein, ZSWIM1 (C20orf162), its gene located on chromosome 20. Its expression is upregulated in lung adenocarcinoma compared with the adjacent normal tissues and negatively correlated with the overall survival. Overexpressing ZSWIM1 markedly promotes the proliferation, migration, invasion as well as epithelial-to-mesenchymal transition in lung adenocarcinoma cells, while knocking down ZSWIM1 functions oppositely. The interactome of ZSWIM1 was identified by immunoprecipitation-mass spectrometry, and we verified the interaction of ZSWIM1 with the potential partner, STK38. ZSWIM1 antagonized the function of STK38. Mechanically, ZSWIM1 promoted the activation of MEKK2/ERK1/2 pathway through interacting with STK38, leading to the release of MEKK2. Taken together, ZSWIM1 can be annotated as an oncogene in lung adenocarcinoma, and the STK38/MEKK2/ERK1/2 axis mediates its promoting role in lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Sistema de Sinalização das MAP Quinases , Fosforilação , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Neoplasias Pulmonares/metabolismo , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo
6.
Funct Integr Genomics ; 23(3): 248, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37474836

RESUMO

Long noncoding RNAs play important roles in the occurrence and development of many malignant cancers. This study focuses on the effects of LINC01087 on gastric cancer and its underlying mechanism. In the present study, LINC01087 and CAAP1 were found to be upregulated, and miR-135a-5p was diminished in gastric cancer specimens and cells. Inhibition of LINC01087 resulted in cell proliferation inhibition and induced cell apoptosis through the intrinsic apoptosis signaling pathway, as evidenced by the activation of caspase-3 and caspase-9. An investigation of the signaling pathway revealed that the effects on proliferation and apoptosis following LINC01087 knockdown were mediated by suppression of CAAP1. Furthermore, application of a miR-135a-5p inhibitor or overexpression of CAAP1 could attenuate the apoptotic effect achieved by LINC01087 inhibition, confirming the involvement of miR-135a-5p/CAAP1 signaling in the occurrence of gastric cancer. In conclusion, the LINC01087/miR-135a-5p/CAAP1 axis modulates gastric cancer tumorigenesis and pathogenesis and presents new insight into gastric cancer targeted therapy.


Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Gástricas/genética , Apoptose/genética , Carcinogênese , Transdução de Sinais , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
7.
Mol Hum Reprod ; 29(9)2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37471586

RESUMO

Circular RNAs (circRNAs), which exert critical functions in the regulation of transcriptional and post-transcriptional gene expression, are found in mammalian cells but their functions in mammalian preimplantation embryo development remain poorly understood. Here, we showed that circKDM5B mediated miRNA-128 (miR-128) to regulate porcine early embryo development. We screened circRNAs potentially expressed in porcine embryos through an integrated analysis of sequencing data from mouse and human embryos, as well as porcine oocytes. An authentic circRNA originating from histone demethylase KDM5B (referred to as circKDM5B) was abundantly expressed in porcine embryos. Functional studies revealed that circKDM5B knockdown not only significantly reduced blastocyst formation but also decreased the number of total cells and trophectoderm (TE) cells. Moreover, the knockdown of circKDM5B resulted in the disturbance of tight junction assembly and impaired paracellular sealing within the TE epithelium. Mechanistically, miR-128 inhibitor injection could rescue the early development of circKDM5B knockdown embryos. Taken together, the findings revealed that circKDM5B functions as a miR-128 sponge, thereby facilitating early embryonic development in pigs through the modulation of gene expression linked to tight junction assembly.


Assuntos
Blastocisto , MicroRNAs , RNA Circular , Animais , Humanos , Camundongos , Blastocisto/metabolismo , Embrião de Mamíferos , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , Mamíferos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Suínos , Histona Desmetilases com o Domínio Jumonji/genética
8.
Ann Surg Oncol ; 30(8): 4783-4796, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37202573

RESUMO

INTRODUCTION: Despite the advances in minimally invasive (MI) liver surgery, most major hepatectomies (MHs) continue to be performed by open surgery. This study aimed to evaluate the risk factors and outcomes of open conversion during MI MH, including the impact of the type of approach (laparoscopic vs. robotic) on the occurrence and outcomes of conversions. METHODS: Data on 3880 MI conventional and technical (right anterior and posterior sectionectomies) MHs were retrospectively collected. Risk factors and perioperative outcomes of open conversion were analyzed. Multivariate analysis, propensity score matching, and inverse probability treatment weighting analysis were performed to control for confounding factors. RESULTS: Overall, 3211 laparoscopic MHs (LMHs) and 669 robotic MHs (RMHs) were included, of which 399 (10.28%) had an open conversion. Multivariate analyses demonstrated that male sex, laparoscopic approach, cirrhosis, previous abdominal surgery, concomitant other surgery, American Society of Anesthesiologists (ASA) score 3/4, larger tumor size, conventional MH, and Institut Mutualiste Montsouris classification III procedures were associated with an increased risk of conversion. After matching, patients requiring open conversion had poorer outcomes compared with non-converted cases, as evidenced by the increased operation time, blood transfusion rate, blood loss, hospital stay, postoperative morbidity/major morbidity and 30/90-day mortality. Although RMH showed a decreased risk of conversion compared with LMH, converted RMH showed increased blood loss, blood transfusion rate, postoperative major morbidity and 30/90-day mortality compared with converted LMH. CONCLUSIONS: Multiple risk factors are associated with conversion. Converted cases, especially those due to intraoperative bleeding, have unfavorable outcomes. Robotic assistance seemed to increase the feasibility of the MI approach, but converted robotic procedures showed inferior outcomes compared with converted laparoscopic procedures.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Fatores de Risco , Tempo de Internação , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento
9.
FASEB J ; 36(8): e22454, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35839067

RESUMO

The peripheral benzodiazepine receptor (TSPO/PBR) is highly conserved among different species but with perplexing biochemical functions. Multiple ligands of TSPO show commendable regulatory activities in lots of biological functions, such as neuro-protection, cholesterol transport, and so on. These researches support that TSPO may be a potential target for disease treatment and drug development. Previous studies have shown that its ligands benzodiazepines show a satisfactory effect on melanogenic promotion. However, the potential application of TSPO in drug development for pigmentary disorder needs further investigation. In this study, we confirmed the melanogenesis induction of TSPO ligand, Ro5-4864 in mouse melanoma cell lines, human skin tissue, and zebrafish embryos by inducing melanin synthesis and melanosome transport. Molecular genetics and pharmacological studies showed that TSPO deficiency did not affect melanin production in B16F10 cells and zebrafish embryos, nor did it affect the melanin promotion effect of Ro5-4864. Whether or not TSPO exists, the expression of lots of melanogenesis-related proteins, such as TYR, TRP-1, DCT, Mlph, and Rab27 was upregulated with the Ro5-4864 administration. These results indicated that Ro5-4864 induces melanogenesis in a TSPO-independent manner, which is inconsistent with previous research. This research is a reminder that we need to be very careful during target validation in drug development.


Assuntos
Melaninas , Receptores de GABA , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Benzodiazepinonas/farmacologia , Benzodiazepinonas/uso terapêutico , Humanos , Ligantes , Melaninas/biossíntese , Melaninas/metabolismo , Melanoma , Camundongos , Receptores de GABA/genética , Receptores de GABA/metabolismo , Receptores de GABA-A/metabolismo , Peixe-Zebra/metabolismo
10.
Ann Hematol ; 102(2): 337-347, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36378304

RESUMO

Acute myeloid leukemia (AML) with NPM1 mutation is a distinct genetic entity with favorable outcomes. Nevertheless, emerging evidence suggests that NPM1-mutated AML is still a highly heterogeneous disorder. In this study, 266 patients with AML with NPM1 mutations were retrospectively analyzed to evaluate the associations between variant allele frequency (VAF) of NPM1 mutations, co-mutated genes, measurable residual disease (MRD), and patient outcomes. Multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (RT-PCR) were used for monitoring MRD. Ultimately, 106 patients were included in the long-term follow-up period. Patients with high NPM1 VAF (≥ 42.43%) had poorer 2-year relapse-free survival (RFS) (55.7% vs. 70.2%, P = 0.017) and overall survival (OS) (63.7% vs. 82.0%, P = 0.027) than those with low VAF. DNMT3A mutations negatively influenced the outcomes of patients with NPM1 mutations. Patients with high DNMT3A VAF or NPM1/DNMT3A/FLT3-ITD triple mutations had shorter RFS and significantly lower OS than that in controls. After two cycles of chemotherapy, patients with positive MFC MRD results had lower RFS (MRD+ vs. MRD-:44.9% vs. 67.6%, P = 0.007) and OS (61.5% vs. 76.6%, P = 0.011) than those without positive MFC MRD results. In multivariate analysis, high NPM1 VAF (hazard ratio [HR] = 2.045; P = 0.034) and positive MRD after two cycles of chemotherapy (HR = 3.289; P = 0.003) were independent risk factors for RFS; MRD positivity after two cycles of chemotherapy (HR = 3.293; P = 0.008) independently predicted the OS of the patients. These results indicate that VAF of both NPM1 gene itself or certain co-occurring gene pre-treatment and MRD post-treatment are potential markers for restratifying the prognoses of patients AML having NPM1 mutations.


Assuntos
Leucemia Mieloide Aguda , Proteínas Nucleares , Humanos , Proteínas Nucleares/genética , Nucleofosmina , Estudos Retrospectivos , Citometria de Fluxo , Prognóstico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Recidiva , Mutação , Neoplasia Residual/genética
11.
Langmuir ; 39(1): 64-74, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36575153

RESUMO

The shedding kinematics of water droplets in a condensation environment when exposed to aerodynamic forces in microgravity was studied. Understanding the shedding of droplets from a surface is a critical part of the dropwise condensation process for improving heat transfer. Because gravity as a droplet removal technique is not available in space, the use of airflow to shed droplets is considered for condensing heat exchangers in environmental control and life support systems. Surface coatings affect drop adhesion, and here, four different surfaces (PMMA, PS, PTFE, and SHS) and various droplet sizes (80, 60, and 40 µL) were used to understand the above phenomenon. It was found that the critical velocity to shed a droplet in microgravity was up to 8% lower than that in normal gravity. Also, the effect of the droplet size was investigated for both microgravity and normal gravity; the shedding velocity was lower for microgravity, and it decreased as droplet size increased. Increasing the hydrophobicity of the coating decreased the critical velocity for shedding. Finally, the droplet was found to detach from superhydrophobic surfaces in microgravity. The detachment of droplets from the substrate will hamper the condensation process that can produce a larger fresh area; also, detachment of droplets and entrainment in airflow counter the concept of removing moisture from the air in a dehumidification process.

12.
Mol Biol Rep ; 50(12): 10301-10313, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37971570

RESUMO

BACKGROUND: Brachyura crab is the largest branch of Decapoda crustacean. Phylogenetic relationships within Brachyura remain controversial to be investigated. The mitochondrial genome (mitogenome) is an important molecular marker for studying the phylogenetic relationships of Brachyura. METHODS AND RESULTS: To understand the phylogeny of Brachyura, the three complete mitogenomes from Charybdis annulata, Leptodius exaratus, and Spider crab were sequenced and annotated. Their full length was 15,747, 15,716, and 16,608 bp long, respectively. The first two crabs both contained 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes and a control region. However, Spider crab contained 13 PCGs, two rRNA genes, 25 tRNA genes and a control region. The mitogenomes of each of the three crabs exhibited high AT content (67.8%, 69.1%, and 70.8%), with negative AT skews (-0.014, - 0.028, and - 0.017) and GC skews (-0.269, - 0.286, and - 0.341). The gene order of C. annulata was identical to the ancestor of Brachyura. Compared with the ancestor of Brachyura, L. exaratus exhibited the gene rearrangements of Val (V)-rrnS-control region, and Spider crab had the four copies of Lys (K). Phylogenetic analyses indicated that C. annulata belonged to Portunidae family, Portunoidea superfamilies, L. exaratus belonged to Xanthidae family, Xanthoidea superfamilies, and Spider crab belonged to Mithracidae family, Majoidea superfamilies. Phylogenetic analyses showed that the two species (Somanniathelphusa boyangensis and Huananpotamon lichuanense) belonging to the Potamoidea were sister groups to the Thoracotremata, thus supporting the conclusion that Heterotremata is polyphyletic. CONCLUSION: The results of this study enriched the crab mitogenome database and enabled us to better understand the phylogenetic relationships of Brachyura.


Assuntos
Braquiúros , Genoma Mitocondrial , Animais , Filogenia , Genoma Mitocondrial/genética , Braquiúros/genética , Rearranjo Gênico/genética , RNA de Transferência/genética
13.
Bioorg Chem ; 141: 106895, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37797456

RESUMO

In this study, twenty-one novel 2,4-diaminopyrimidine cinnamyl derivatives as inhibitors targeting FAK were designed and synthesized based on the structure of TAE-226, and the inhibitory effects of these compounds on both the FAK enzyme and three cancer cell lines (MGC-803, HCT-116, and KYSE30) were investigated. Among them, compound 12s displayed potent inhibitory potency on FAK (IC50 = 47 nM), and demonstrated more significant antiproliferative activities in MGC-803, HCT-116 and KYSE30 cells (IC50 values were 0.24, 0.45 and 0.44 µM, respectively) compared to TAE-226. Furthermore, compound 12s significantly inhibited FAK activation leading to the negative regulation of FAK-related signaling pathways such as AKT/mTOR and MAPK signaling pathways. Molecular docking study suggested that compound 12s could well occupy the ATP-binding pocket site of FAK similar to TAE-226. In addition, compound 12s also efficiently inhibited the proliferation, induced apoptosis and cellular senescence in MGC-803 cells. In conclusion, compound 12s emerges a potent FAK inhibitor that could exert potent inhibitory activity against gastric cancer cells.


Assuntos
Antineoplásicos , Neoplasias Gástricas , Humanos , Relação Estrutura-Atividade , Antineoplásicos/química , Simulação de Acoplamento Molecular , Neoplasias Gástricas/tratamento farmacológico , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases
14.
Surg Endosc ; 37(5): 3439-3448, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36542135

RESUMO

BACKGROUND: Left lateral sectionectomy (LLS) is one of the most commonly performed minimally invasive liver resections. While laparoscopic (L)-LLS is a well-established technique, over traditional open resection, it remains controversial if robotic (R)-LLS provides any advantages of L-LLS. METHODS: A post hoc analysis of 997 patients from 21 international centres undergoing L-LLS or R-LLS from 2006 to 2020 was conducted. A total of 886 cases (214 R-LLS, 672 L-LLS) met study criteria. 1:1 and 1:2 propensity score matched (PSM) comparison was performed between R-LLS & L-LLS. Further subset analysis by Iwate difficulty was also performed. Outcomes measured include operating time, blood loss, open conversion, readmission rates, morbidity and mortality. RESULTS: Comparison between R-LLS and L-LLS after PSM 1:2 demonstrated statistically significantly lower open conversion rate in R-LLS than L-LLS (0.6% versus 5%, p = 0.009) and median blood loss was also statistically significantly lower in R-LLS at 50 (80) versus 100 (170) in L-LLS (p = 0.011) after PSM 1:1 although there was no difference in the blood transfusion rate. Pringle manoeuvre was also found to be used more frequently in R-LLS, with 53(24.8%) cases versus to 84(12.5%) L-LLS cases (p < 0.001). There was no significant difference in the other key perioperative outcomes such as operating time, length of stay, postoperative morbidity, major morbidity and 90-day mortality between both groups. CONCLUSION: R-LLS was associated with similar key perioperative outcomes compared to L-LLS. It was also associated with significantly lower blood loss and open conversion rates compared to L-LLS.


Assuntos
Laparoscopia , Neoplasias Hepáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Pontuação de Propensão , Resultado do Tratamento , Tempo de Internação , Estudos Retrospectivos , Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
15.
BMC Geriatr ; 23(1): 494, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587447

RESUMO

BACKGROUND: Sarcopenia is commonly seen in the older adults and increases in incidence with age, also in Parkinson's disease (PD). Although research has indicated that the development of sarcopenia in patients with PD may be related to both motor symptoms and non-motor symptoms (NMS), the precise relationship between the two conditions remains unclear. Therefore, we aimed to investigate the incidence of sarcopenia in patients with PD and its association with NMS. METHODS: The study included 123 patients with PD and 38 age- and sex-matched healthy controls (HC). All participants were evaluated for sarcopenia using the 2019 Asian Sarcopenia Diagnostic Criteria, and patients with PD underwent standard assessments of motor symptoms and NMS. Multiple logistic regression and receiver operating characteristic (ROC) curve analyses were used to examine the association between sarcopenia and NMS in patients with PD. RESULTS: The incidence of sarcopenia was significantly higher in patients with PD than in HC (26.8% vs. 10.4%, p = 0.046). Multiple logistic regression analysis revealed that poorer sleep quality (odds ratio [OR]: 1.245; 95% confidence interval [CI]: 1.011-1.533; p = 0.040) and fatigue (OR: 1.085, 95% CI: 1.006-1.170, p = 0.034) were independently associated with sarcopenia. ROC analysis indicated that the optimal cut-off value for Pittsburgh Sleep Quality Index (PSQI) scores was 10, with 72.7% sensitivity and 74.4% specificity (area under the curve [AUC] = 0.776, 95% CI: 0.683-0.868, p < 0.001). The optimal cut-off value for Fatigue Severity Scale (FSS) scores was 39, with 87% sensitivity and 50% specificity (AUC = 0.725, 95% CI: 0.629 -0.820, p < 0.001). Joint use of FSS and PSQI scores increased the predictive value for sarcopenia(AUC = 0.804, 95% CI: 0.724-0.885, p < 0.001). CONCLUSION: Patients with PD are more susceptible to sarcopenia than healthy older adults, and fatigue and poorer sleep are positively associated with sarcopenia. Further longitudinal studies are needed to clarify the causal relationships.


Assuntos
Doença de Parkinson , Sarcopenia , Humanos , Idoso , Estudos Transversais , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , População do Leste Asiático , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Fadiga
16.
Yi Chuan ; 45(5): 409-424, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-37194588

RESUMO

The circadian clock exists in almost all life forms, and is an internal activity generated by organisms adapting to the daily periodic changes of the external environment. The circadian clock is regulated by the transcription-translation-negative feedback loop in the body, which can regulate the activities of tissues and organs. Its normal maintenance is important for the health, growth, and reproduction of organisms. In contrast, due to the season changes of the environment, organisms have also formed annual cycle physiological changes in their bodies, such as seasonal estrus, etc. The annual rhythm of living things is mainly affected by environmental factors such as photoperiod, and is related to gene expression, hormone content, morphological changes of cell and tissues in vivo. Melatonin is an important signal to recognize the changes of photoperiod, and the circadian clock plays an important role in the pituitary to interpret the signal of melatonin and regulate the changes of downstream signals, which plays an important guiding role in the recognition of annual changes in the environment and the generation of the body's annual rhythm. In this review, we summarize the progress of research on the mechanism of action of circadian clocks in influencing annual rhythms, by introducing the mechanisms of circadian and annual rhythms generation in insects and mammals, and in the context of annual rhythms in birds, with the aim of providing a broader range of ideas for future research on the mechanism of annual rhythms influence.


Assuntos
Relógios Circadianos , Melatonina , Animais , Feminino , Ritmo Circadiano/genética , Melatonina/metabolismo , Fotoperíodo , Estações do Ano , Mamíferos/metabolismo
17.
Indian J Microbiol ; 63(1): 146-151, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37188240

RESUMO

Sucrose non-fermenting 1 (SNF1) protein kinase plays an important role in the utilization of selective carbon sources and regulation of lipid metabolism. In order to further explore the function of SNF1 in regulating lipid accumulation by responding nutritional signals from non-glucose carbon sources, in the present study, the lipid production and SNF1 transcriptional levels of Mucor circinelloides were analyzed and compared on different carbon sources. The results indicated that M. circinelloides could effectively utilize some secondary metabolic carbon sources of monosaccharides and disaccharides for growth and lipids production, such as fructose, maltose and galactose. Snf-ß subunit was associated with the regulation of lipid metabolism in response to nutritional signals from different carbon sources. This is the first report on the transcriptional analysis of SNF1 subunits on different carbons metabolism in oleaginous filamentous fungi. This research has suggested that genetic engineering of SNF1 subunits will alter the lipid production of M. circinelloides from alternative carbon sources. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01070-z.

19.
Glob Chang Biol ; 28(1): 154-166, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34651373

RESUMO

No-till (NT) is a sustainable option because of its benefits in controlling erosion, saving labor, and mitigating climate change. However, a comprehensive assessment of soil pH response to NT is still lacking. Thus, a global meta-analysis was conducted to determine the effects of NT on soil pH and to identify the influential factors and possible consequences based on the analysis of 114 publications. When comparing tillage practices, the results indicated an overall significant decrease by 1.33 ± 0.28% in soil pH under NT than that under conventional tillage (p < .05). Soil texture, NT duration, mean annual temperature (MAT), and initial soil pH are the critical factors affecting soil pH under NT. Specifically, with significant variations among subgroups, when compared to conventional tillage, the soil under NT had lower relative changes in soil pH observed on clay loam soil (-2.44%), long-term implementation (-2.11% for more than 15 years), medium MAT (-1.87% in the range of 8-16℃), neutral soil pH (-2.28% for 6.5 < initial soil pH < 7.5), mean annual precipitation (-1.95% in the range of 600-1200 mm), in topsoil layers (-2.03% for 0-20 cm), with crop rotation (-1.98%), N fertilizer input (the same for NT and conventional tillage) of 100-200 kg N ha-1 (-1.83%), or crop residue retention (-1.52%). Changes in organic matter decomposition under undisturbed soil and with crop residue retention might lead to a higher concentration of H+ and lower of basic cations (i.e., calcium, magnesium, and potassium), which decrease the soil pH, and consequently, impact nutrient dynamics (i.e., soil phosphorus) in the surface layer under NT. Furthermore, soil acidification may be aggravated by NT within site-specific conditions and improper fertilizer and crop residue management and consequently leading to adverse effects on soil nutrient availability. Thus, there is a need to identify strategies to ameliorate soil acidification under NT to minimize the adverse consequences.


Assuntos
Agricultura , Solo , Mudança Climática , Fertilizantes , Concentração de Íons de Hidrogênio
20.
Int J Colorectal Dis ; 37(11): 2397-2407, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36301375

RESUMO

BACKGROUND: Small intestine adenocarcinoma (SIA) is a scant disease that has no adequate clinical trials, so its prognostic factors are still unclear, especially in elderly patients. In this article, we aimed to explore the clinicopathology presentation, treatments, outcomes, and predictors of small intestine adenocarcinoma patients aged 65 years or older. METHODS: We retrieved clinicopathology data of small intestine adenocarcinoma patients diagnosed between 2004 and 2015 from the Surveillance Epidemiology and End Results (SEER) database. We clarified patients into two groups: the surgery and the non-surgery group and conducted propensity score matching (PSM) to compare survival outcoming. We identified the prognostic indicators for cancer-specific survival (CSS) and overall survival (OS) by the Cox proportional hazards model. RESULTS: In total, 1018 eligible cases were enrolled, with a median survival of 16 months; the 3-year OS and CSS rates were 36% and 41.7%, and the 5-year OS and CSS rates were 26.5% and 33.3%. Multivariate analyses revealed that age, grade, tumor stage, surgery, and chemotherapy were independent prognostic factors for OS, while grade, tumor stage, surgery, radiation, and chemotherapy were independent factors for CSS. After PSM, only surgery and tumor stage (AJCC 6th) were independent prognostic factors for OS and CSS. CONCLUSION: Surgery could bring benefit to survival for elderly SIA patients, and the early stage of the disease was another significant prognostic factor.


Assuntos
Adenocarcinoma , Idoso , Humanos , Pontuação de Propensão , Prognóstico , Programa de SEER , Estadiamento de Neoplasias , Adenocarcinoma/patologia , Intestino Delgado/patologia
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