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1.
Nucleic Acids Res ; 51(4): 1823-1842, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36660855

RESUMO

Photosynthesis is the most temperature-sensitive process in the plant kingdom, but how the photosynthetic pathway responds during low-temperature exposure remains unclear. Herein, cold stress (4°C) induced widespread damage in the form DNA double-stranded breaks (DSBs) in the mesophyll cells of rice (Oryza sativa), subsequently causing a global inhibition of photosynthetic carbon metabolism (PCM) gene expression. Topoisomerase genes TOP6A3 and TOP6B were induced at 4°C and their encoded proteins formed a complex in the nucleus. TOP6A3 directly interacted with KU70 to inhibit its binding to cold-induced DSBs, which was facilitated by TOP6B, finally blocking the loading of LIG4, a component of the classic non-homologous end joining (c-NHEJ) pathway. The repression of c-NHEJ repair imposed by cold extended DSB damage signaling, thus prolonging the inhibition of photosynthesis in leaves. Furthermore, the TOP6 complex negatively regulated 13 crucial PCM genes by directly binding to their proximal promoter regions. Phenotypically, TOP6A3 overexpression exacerbated the γ-irradiation-triggered suppression of PCM genes and led to the hypersensitivity of photosynthesis parameters to cold stress, dependent on the DSB signal transducer ATM. Globally, the TOP6 complex acts as a signal integrator to control PCM gene expression and synchronize cold-induced photosynthesis inhibition, which modulates carbon assimilation rates immediately in response to changes in ambient temperature.


Assuntos
DNA Topoisomerases , Oryza , Fotossíntese , Carbono/metabolismo , Reparo do DNA por Junção de Extremidades , Reparo do DNA , Proteínas de Ligação a DNA/genética , Células do Mesofilo/metabolismo , Oryza/enzimologia , Oryza/fisiologia , DNA Topoisomerases/fisiologia , Temperatura Baixa
2.
Bioorg Med Chem Lett ; 58: 128526, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34998903

RESUMO

The COVID-19 pandemic has drastically impacted global economies and public health. Although vaccine development has been successful, it was not sufficient against more infectious mutant strains including the Delta variant indicating a need for alternative treatment strategies such as small molecular compound development. In this work, a series of SARS-CoV-2 main protease (Mpro) inhibitors were designed and tested based on the active compound from high-throughput diverse compound library screens. The most efficacious compound (16b-3) displayed potent SARS-CoV-2 Mpro inhibition with an IC50 value of 116 nM and selectivity against SARS-CoV-2 Mpro when compared to PLpro and RdRp. This new class of compounds could be used as potential leads for further optimization in anti COVID-19 drug discovery.


Assuntos
Antivirais/farmacologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Descoberta de Drogas , Inibidores de Proteases/farmacologia , SARS-CoV-2/efeitos dos fármacos , Tiazóis/farmacologia , Antivirais/síntese química , Antivirais/química , Proteases 3C de Coronavírus/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Inibidores de Proteases/síntese química , Inibidores de Proteases/química , SARS-CoV-2/enzimologia , Tiazóis/síntese química , Tiazóis/química , Tratamento Farmacológico da COVID-19
3.
BMC Infect Dis ; 22(1): 280, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35321647

RESUMO

BACKGROUND: Deep neck space abscess (DNSA) is a serious infection in the head and neck. Antibiotic therapy is an important treatment in patients with DNSA. However, the results of bacterial culture need at least 48 h, and the positive rate is only 30-50%, indicating that the use of empiric antibiotic treatment for most patients with DNSA should at least 48 h or even throughout the whole course of treatment. Thus, how to use empiric antibiotics has always been a problem for clinicians. This study analyzed the distribution of bacteria based on disease severity and clinical characteristics of DNSA patients, and provides bacteriological guidance for the empiric use of antibiotics. METHODS: We analyzed 433 patients with DNSA who were diagnosed and treated at nine medical centers in Guangdong Province between January 1, 2015, and December 31, 2020. A nomogram for disease severity (mild/severe) was constructed using least absolute shrinkage and selection operator-logistic regression analysis. Clinical characteristics for the Gram reaction of the strain were identified using multivariate analyses. RESULTS: 92 (21.2%) patients developed life-threatening complications. The nomogram for disease severity comprised of seven predictors. The area under the receiver operating characteristic curves of the nomogram in the training and validation cohorts were 0.951 and 0.931, respectively. In the mild cases, 43.2% (101/234) had positive culture results (49% for Gram-positive and 51% for Gram-negative strains). The positive rate of cultures in the patients with severe disease was 63% (58/92, 37.9% for Gram-positive, and 62.1% for Gram-negative strains). Diabetes mellitus was an independent predictor of Gram-negative strains in the mild disease group, whereas gas formation and trismus were independent predictors of Gram-positive strains in the severe disease group. The positivity rate of multidrug-resistant strains was higher in the severe disease group (12.1%) than in the mild disease group (1.0%) (P < 0.001). Metagenomic sequencing was helpful for the bacteriological diagnosis of DNSA by identifying anaerobic strains (83.3%). CONCLUSION: We established a DNSA clinical severity prediction model and found some predictors for the type of Gram-staining strains in different disease severity cases. These results can help clinicians in effectively choosing an empiric antibiotic treatment.


Assuntos
Abscesso , Pescoço , Abscesso/tratamento farmacológico , Abscesso/microbiologia , Antibacterianos/uso terapêutico , Humanos , Metagenômica , Pescoço/microbiologia , Índice de Gravidade de Doença
4.
Mol Ther ; 26(12): 2766-2778, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30217729

RESUMO

Neurotropic infiltrative growth and distant metastasis are the main causes of death in salivary adenoid cystic carcinoma (SACC) patients. Long noncoding RNAs (lncRNAs) are involved in many human neoplasms, however, their potential roles in SACC are unclear. In our study, we found that ADAM metallopeptidase with thrombospondin type 1 motif, 9 (ADAMTS9) antisense RNA 2 (ADAMTS9-AS2) was significantly upregulated in SACC patients with metastasis and SACC-lung metastasis (LM) cells. Moreover, ADAMTS9-AS2 expression was closely associated with the prognosis and distant metastasis in SACC patients. Next, we found that c-myc could specifically bind to the promoter of ADAMTS9-AS2 and activated its transcription. Knockdown of ADAMTS9-AS2 significantly inhibited migration and invasion of SACC cells in vitro and distant lung metastasis in vivo. Furthermore, ADAMTS9-AS2, which mainly expressed in the cytoplasm, shared microRNA (miRNA) response elements with Integrin α6 (ITGA6). Overexpression of ADAMTS9-AS2 competitively bound to miR-143-3p that inhibited ITGA6 from miRNA-mediated degradation, and thus it activated the activity of PI3K/Akt and MEK/Erk signaling and facilitated SACC metastasis. In summary, ADAMTS9-AS2 promotes migration and invasion in SACC by competing with miR-143-3p. This sheds a new insight into the regulation mechanism of ADAMTS9-AS2, and it provides a possible application for the SACC treatment.


Assuntos
Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/metabolismo , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismo , Transdução de Sinais , Animais , Biomarcadores Tumorais , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Modelos Animais de Doenças , Humanos , Sistema de Sinalização das MAP Quinases , Camundongos , MicroRNAs/genética , Metástase Neoplásica , Estadiamento de Neoplasias , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/patologia
5.
Mol Ther ; 26(6): 1494-1508, 2018 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-29699939

RESUMO

Increasing evidence has shown that chemo-resistance is related to the process of epithelial-mesenchymal transition (EMT) and increased invasiveness by tongue squamous cell carcinoma (TSCC) cells. Long non-coding RNAs (lncRNAs) play pivotal roles in tumor metastasis and progression. However, the roles and mechanisms of lncRNAs in cisplatin-resistance-induced EMT and metastasis are not well understood. In this study, a chemotherapy-induced lncRNA 1 (CILA1) was discovered by using microarrays and was functionally identified as a regulator of chemo-sensitivity in TSCC cells. Upregulation of CILA1 promotes EMT, invasiveness, and chemo-resistance in TSCC cells, whereas the inhibition of CILA1 expression induces mesenchymal-epithelial transition (MET) and chemo-sensitivity, and inhibits the invasiveness of cisplatin-resistant cells both in vitro and in vivo. We also found that CILA1 exerts its functions via the activation of the Wnt/ß-catenin signaling pathway. High CILA1 expression levels and low levels of phosphorylated ß-catenin were closely associated with cisplatin resistance and advanced disease stage, and were predictors of poor prognosis in TSCC patients. These findings provided a new biomarker for the chemo-sensitivity of TSCC tumors and a therapeutic target for TSCC treatment.


Assuntos
Antineoplásicos/uso terapêutico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , RNA Longo não Codificante/genética , Neoplasias da Língua/tratamento farmacológico , Neoplasias da Língua/metabolismo , Via de Sinalização Wnt/fisiologia , beta Catenina/isolamento & purificação , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias da Língua/genética , Via de Sinalização Wnt/genética , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/genética
6.
Surg Endosc ; 31(8): 3203-3209, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27864725

RESUMO

BACKGROUND: A few modified approaches have been reported for performing endoscope-assisted dissections of benign parotid tumors, but none that use incisions totally hidden in a natural furrow. This study evaluated the feasibility of performing endoscope-assisted extracapsular dissections of benign parotid tumors using a single cephaloauricular furrow incision. METHODS: Forty-six patients with benign parotid superficial lobe tumors were randomly divided into two groups: an endoscope-assisted (21 patients) group or a conventional (25 patients) surgery group. Perioperative and postoperative outcomes of the patients were evaluated, including the maximum diameter of the tumors, length of the incision, operating time, estimated blood loss during the operation, amount and duration of drainage, satisfaction scores based on the cosmetic results, perioperative complications, and follow-up information. RESULTS: The diameters of the tumors were comparable between the groups, and all operations were successfully performed as planned. The mean length of the incision in the endoscope-assisted group (3.6 ± 0.5 cm) was significantly shorter than that in the conventional group (9.1 ± 1.9). Meanwhile, the intraoperative blood loss, amount of drainage, perioperative complications, and cosmetic outcomes were all improved in the endoscope-assisted group. No tumor recurrence was found during 11-40 months of follow-up. CONCLUSIONS: Cephaloauricular furrow incisions were totally and naturally hidden in this procedure. Endoscope-assisted extracapsular dissections of benign parotid tumors via a small cephaloauricular furrow incision were found to be feasible and reliable, providing a minimally invasive approach and a satisfactory appearance.


Assuntos
Recidiva Local de Neoplasia/cirurgia , Neoplasias Parotídeas/cirurgia , Adulto , Perda Sanguínea Cirúrgica , Pavilhão Auricular/cirurgia , Endoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias , Resultado do Tratamento , Adulto Jovem
7.
Int J Mol Sci ; 16(1): 1576-89, 2015 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-25588213

RESUMO

Ponicidin has a variety of biological effects such as immunoregulatory and anti-inflammatory functions as well as anti-viral functions especially in the upper respiratory tract infection. This study was aimed to elucidate the antitumor effect of ponicidin in gastric carcinoma MKN28 cells and the possible molecular mechanism involved. Cell viability was measured by the Cell Count Kit-8 (CCK8). Cell apoptosis was assessed by flow cytometry as well as cell cycle and reactive oxygen species (ROS) analysis. Western blot analysis was used to detect the active form of caspase-3 as well as Bax and B-cell lymphoma-2 (Bcl-2) expressions after cells were treated with different concentrations of ponicidin. The results revealed that ponicidin could inhibit the growth of MKN28 cells significantly in both a time- and dose-dependent manner. The cell cycle was blocked and ROS generation was increased after the cells were treated with ponicidin. Bcl-2 expression was down-regulated remarkably while Bax expression and the active form of caspase-3 were increased after apoptosis occurred. We therefore conclude that ponicidin exhibited significant growth inhibition of gastric carcinoma cell line MKN28 and induced apoptosis of MKN28 cells via the signaling pathway regulated by Janus kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3). Ponicidin may serve as a potential therapeutic agent for gastric carcinoma.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Diterpenos/farmacologia , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Antivirais/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Mucosa Gástrica/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estômago/efeitos dos fármacos , Estômago/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
8.
Ann Surg Oncol ; 21(12): 3876-81, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24912615

RESUMO

BACKGROUND: Selective neck dissection (SND) in clinical N0 (cN0) cases of oral squamous cell carcinoma (SCC) has been performed by surgeons using a retroauricular or modified facelift approach with robotic or endoscopic assistance. However, these procedures provide cosmetic satisfaction at the cost of possible maximal invasiveness. In this prospective study, we introduced and evaluated the feasibility as well as surgical invasiveness and cosmetic outcome of endoscopically-assisted SND via a small submandibular approach. METHODS: Forty-four patients with cT1-2N0 oral SCC (OSCC) were randomly divided into two groups of endoscopically-assisted SND and conventional SND. Perioperative and postoperative outcomes of patients were evaluated, including the length of the incision, operating time for neck dissection, estimated blood loss during the operation, amount and duration of drainage, total hospitalization period, total number of lymph nodes retrieved, satisfaction scores based on the cosmetic results, perioperative local complications, shoulder syndrome, and follow-up information. RESULTS: The mean operation time in the endoscopically-assisted group (126.04 ± 12.67 min) was longer than that in the conventional group (75.67 ± 16.67 min). However, the mean length of the incision was 4.33 ± 0.76 cm in the endoscopically-assisted SND group, and the amount and duration of drainage, total hospital stay, postoperative shoulder pain score, and cosmetic outcomes were superior in the endoscopically-assisted SND group. Additionally, the retrieved lymph nodes and complications were comparable. CONCLUSIONS: Endoscopically-assisted SND via a small submandibular approach had a longer operation time than the conventional approach. However, endoscopically-assisted SND was feasible and reliable while providing minimal invasiveness and satisfactory appearance.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Endoscopia , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias Bucais/cirurgia , Esvaziamento Cervical/métodos , Glândula Submandibular/cirurgia , Carcinoma de Células Escamosas/patologia , Estudos de Viabilidade , Seguimentos , Humanos , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Duração da Cirurgia , Procedimentos Cirúrgicos Bucais , Complicações Pós-Operatórias , Prognóstico , Estudos Prospectivos
9.
Clin Invest Med ; 37(1): E1-9, 2014 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-24502806

RESUMO

PURPOSE: Tetramethylpyrazine (TMP) is an effective Chinese plant-derived medicine for colitis in the clinic, but the underlying molecular mechanisms of its use remain poorly understood. The purpose of this study was to investigate the mechanisms involved in its therapeutic action. METHODS: A colitis mouse model was induced by oxazolone enema. TMP was administered at 80 mg/kg/day and sulphasalazine (SASP) was used as positive control and administered at 100 mg/kg/day for the treatment of colitis. On the fourth day after enema, mice were sacrificed. The inflammatory response was assessed by the disease activity index and histology. Colon mucosa was isolated and biochemically analyzed. In addition, in vitro studies were performed to evaluate the activity of TMP in Caco-2 cells. RESULTS: Our results showed that TMP improved the colonic inflammatory status as evidenced by histological findings, as well as SASP. These effects were associated with a decrease in nucleus translocation of NF-κB. Paired with this inhibitive activity, there was a decrease in downstream signaling, such as C-MYC, iNOS and COX-2. In vitro assays revealed that TMP inhibited NF-κB translocation and its downstream production of inflammatory factors, such as TNF-α, IL-6 and IL-8, and that ROS production that was induced by LPS in Caco-2 cells. CONCLUSION: TMP improved the colitis induced by oxazoline, and its activity was associated with inhibition of NF-κB translocation, and subsequent inhibition of pro-inflammatory factor production and oxidative stress.


Assuntos
Colite/tratamento farmacológico , Colite/metabolismo , NF-kappa B/antagonistas & inibidores , Pirazinas/uso terapêutico , Animais , Células CACO-2 , Colite/induzido quimicamente , Citocinas/biossíntese , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos , Oxazolona/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Transdução de Sinais/efeitos dos fármacos
10.
Eur Arch Otorhinolaryngol ; 271(10): 2789-93, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24292216

RESUMO

The aim of the study is to report the feasibility of endoscope-assisted second branchial cleft cyst resection via a small incision along the skin line on the lateral neck. In total, 41 patients from the Department of Otolaryngology, Foshan Hospital of Yat-sen University were randomly assigned to conventional (20 patients) or endoscope-assisted (21 patients) second branchial cleft cyst resection. The patient clinical characteristics, operation time, operative bleeding volume, postoperative complications, and subjective satisfaction with the incision scar (measured using a visual analog scale) were compared between the groups. All 41 s branchial cleft cyst resections were successfully performed, and the wounds healed uneventfully. The bleeding volume (6.3 ± 2.5 ml) and incision length (2.7 ± 0.3 cm) differed between the groups (P < 0.00). The mean patient satisfaction score was 8.0 ± 0.8 in the endoscope-assisted surgery group and 6.4 ± 0.9 in the control group (P < 0.00). All of the patients in the endoscope-assisted surgery group were satisfied with their cosmetic results. No marginal nerve palsy occurred. No complications such as bleeding, salivary fistula, or paresis of the marginal mandibular branch occurred. All of the patients were disease free through a follow-up period of 6-24 months (median: 14 months). Endoscope-assisted second branchial cleft cyst resection via a small incision along the dermatoglyph on the lateral neck is a feasible technique. This procedure may serve as an alternative approach, allowing a minimally invasive incision and better cosmetic results.


Assuntos
Branquioma/cirurgia , Endoscópios , Endoscopia/métodos , Neoplasias de Cabeça e Pescoço/cirurgia , Pescoço/cirurgia , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
11.
Artigo em Inglês | MEDLINE | ID: mdl-24861138

RESUMO

OBJECTIVES: The aim of this study was to evaluate the feasibility of an endoscope-assisted partial parotidectomy through a modified retroauricular incision. PATIENTS AND METHODS: Thirty patients with benign parotid superficial lobe tumors with a diameter of 2.4 ± 0.5 cm, located in the anterior portion of the inferior auricular lobule, underwent an endoscope-assisted partial-superficial parotidectomy. A retrograde approach through a small skin incision was used. An additional 30 patients who underwent conventional surgeries were used as controls. The operation time, operative bleeding volume and subjective satisfaction with the incision scar were compared between the groups. RESULTS: All operations were successfully performed. The endoscopic surgery duration (74.8 ± 15.7 min), bleeding volume (12.7 ± 3.9 ml) and incision length (4.8 ± 0.4 cm) differed between the groups (p = 0.001). The mean patient satisfaction score was 8.6 ± 1.2 in the endoscope-assisted surgery group and 5.4 ± 1.3 in the control group (p = 0.001). There were no tumor recurrences during the 9-36 months of follow-up. CONCLUSION: Endoscope-assisted partial-superficial parotidectomy via a modified retroauricular incision is a feasible method for the treatment of benign parotid superficial lobe tumors located in the anterior portion of the inferior auricular lobule. The main advantage of this procedure was that the small operative scars improved the cosmetic results.


Assuntos
Endoscopia/métodos , Glândula Parótida/cirurgia , Neoplasias Parotídeas/cirurgia , Adulto , Idoso , Endoscopia/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Resultado do Tratamento
12.
Pharm Biol ; 52(6): 789-95, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24824325

RESUMO

CONTEXT: Oleanolic acid (OA) belongs to the triterpenoid compound group existing widely in food, medicinal herbs and other plants. Its effects on gastric cancer cells and the mechanisms involved have not been investigated. OBJECTIVE: This study aimed to substantiate whether OA induces apoptosis of gastric cancer cell line (MKN28) and to elucidate the molecular mechanism involved. MATERIALS AND METHODS: Cell viability was assessed by MTT assay within the range of 0-160 µg/mL. The effects of OA (5, 10 and 20 µg/mL) on apoptosis of MKN28 cells were evaluated by flow cytometry, DNA fragmentation and mitochondrial membrane potential assays. Western blot and FQRT-PCR assays were used to investigate the mechanism of cell apoptosis induced by OA (5 and 10 µg/mL). RESULTS: OA evidently inhibited cell viability with IC50 of 44.8 and 15.9 µg/mL at 12 and 24 h, respectively. Furthermore, OA increased JNK phosphorylation, decreased AKT phosphorylation, but did not affect p38 and ERK phosphorylation in MKN28 cells. In contrast, OA also significantly enhanced the mRNA expression levels of caspase 3, caspase 9 and Apaf-1 in MKN28 cells. CONCLUSION: OA induces apoptosis of MKN28 cells via the mitochondrial pathway regulated by AKT and JNK signaling pathways.


Assuntos
Apoptose/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Ácido Oleanólico/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo
13.
Head Neck ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488177

RESUMO

BACKGROUNDS: A deep neck space abscess (DNSA) is a critical condition resulting from infection of deep neck fascia and soft issue, leading to high morbidity and mortality. Therefore, intensive care can be very significant for patients with DNSA. This study aimed to develop models to predict the need for postoperative intensive care in patients with DNSA. METHODS: We retrospectively analyzed the records of 332 patients with DNSA who received drainage operation between 2015 and 2020. Multivariate logistic regression analysis and the eXtrem Gradient Boosting (XGBoost) algorithm were used to develop predictive models. RESULTS: We developed two predictive models, the nomogram and the XGBoost model. The area under the curve (AUC) of the nomogram was 0.911 and of the XGBoost model was 0.935. CONCLUSION: We developed two predictive models for guiding clinical decision making for postoperative ICU admission for DNSA patients, which may help improve prognosis and optimize intensive care resource allocation.

14.
Clin Cosmet Investig Dermatol ; 17: 1527-1541, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948922

RESUMO

Purpose: This study seeks to investigate the effect of evodiamine on psoriasis and psoriatic pruritus. Methods: Imiquimod-induced psoriasiform dermatitis in mice was used as a model, and evodiamine was topically applied for seven days. The mice were observed daily for skin damage on the back, clinical score and their scratching behavior was recorded. Blood samples were collected on the final day of the experiment, and the serum levels of pruritus-associated inflammatory cytokines tumor necrosis factor (TNF) -α, interleukin (IL) -23, and IL-17A were measured using enzyme-linked immunosorbent assay. Histopathological changes were observed in Hematoxylin and Eosin-stained skin specimens. The expression levels of transient receptor potential vanilloid (TRPV) 1, TRPV3, TRPV4, and the pruritus-related mediators Substance P (SP), nerve growth factor (NGF), and calcitonin gene-related peptide (CGRP) in the skin lesions were analyzed using Western blot and qRT-PCR. The effect of evodiamine on the exploratory behavior, motor, and coordination abilities of mice was assessed using open field, suspension, and Rota-Rod experiments. Molecular docking was utilized to verify the binding of evodiamine to the residues of TRPV1, TRPV3, and TRPV4. Results: Evodiamine reduced pruritus and inhibited inflammation by decreasing the levels of inflammatory mediators TNF-α, IL-23, and IL-17A in the serum of Imiquimod-induced mice and attenuated the mRNA and protein expression levels of SP, NGF, CGRP, TRPV1, TRPV3, and TRPV4 in the skin. Conclusion: Evodiamine is an effective treatment for psoriasis and pruritus, due to its ability to inhibit immune inflammation and pruritic mediators.

15.
Plants (Basel) ; 13(10)2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38794481

RESUMO

Bacterial leaf blight (BLB), among the most serious diseases in rice production, is caused by Xanthomonas oryzae pv. oryzae (Xoo). Xa23, the broadest resistance gene against BLB in rice, is widely used in rice breeding. In this study, the rice variety CBB23 carrying the Xa23 resistance gene was inoculated with AH28 and PXO99A to identify differentially expressed genes (DEGs) associated with the resistance. Transcriptome sequencing of the infected leaves showed 7997 DEGs between the two strains at different time points, most of which were up-regulated, including cloned rice anti-blight, peroxidase, pathology-related, protein kinase, glucosidase, and other coding genes, as well as genes related to lignin synthesis, salicylic acid, jasmonic acid, and secondary metabolites. Additionally, the DEGs included 40 cloned, five NBS-LRR, nine SWEET family, and seven phenylalanine aminolyase genes, and 431 transcription factors were differentially expressed, the majority of which belonged to the WRKY, NAC, AP2/ERF, bHLH, and MYB families. Metabolomics analysis showed that a large amount of alkaloid and terpenoid metabolite content decreased significantly after inoculation with AH28 compared with inoculation with PXO99A, while the content of amino acids and their derivatives significantly increased. This study is helpful in further discovering the pathogenic mechanism of AH28 and PXO99A in CBB23 rice and provides a theoretical basis for cloning and molecular mechanism research related to BLB resistance in rice.

16.
Eur J Med Chem ; 240: 114608, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35872393

RESUMO

Ebola virus (EBOV), one member of the family Filoviridae, can causes hemorrhagic fever and other severe diseases in humans with a high mortality rate (25-90%). Until recently, there were no approved drugs and very limited treatment method for Ebola virus disease. In this study, we discovered a series of potent Ebola entry inhibitors with the (3S,4aS,8aS)-2-(3-amino-2-hydroxypropyl)decahydroisoquinoline-3-carboxamide scaffold from high-throughput screening in reported pseudotyped virus system. Further optimization resulted a most potent compound 28 (IC50= 0.05 µM, SI = 98), which displayed 3-fold potency compared to the known inhibitor Toremifene (IC50= 0.17 µM, SI = 55). Moreover, compound 28 exhibited the remarkable selectivity between EBOV-GP and VSV-G (Spec. Index = 58), thus could exclude nonspecific effects. Structure-activity relationship and molecular docking analysis of the new chemical scaffold provided more information on the binding modes and the spare volume at the binding cavity, thus can guide the design of the further potent compounds.


Assuntos
Ebolavirus , Inibidores da Fusão de HIV , Doença pelo Vírus Ebola , Antivirais/química , Inibidores da Fusão de HIV/farmacologia , Doença pelo Vírus Ebola/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Internalização do Vírus
18.
Nat Commun ; 13(1): 3882, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35794100

RESUMO

Mitochondrial dynamics can regulate Major Histocompatibility Complex (MHC)-I antigen expression by cancer cells and their immunogenicity in mice and in patients with malignancies. A crucial role in the mitochondrial fragmentation connection with immunogenicity is played by the IRE1α-XBP-1s axis. XBP-1s is a transcription factor for aminopeptidase TPP2, which inhibits MHC-I complex cell surface expression likely by degrading tumor antigen peptides. Mitochondrial fission inhibition with Mdivi-1 upregulates MHC-I expression on cancer cells and enhances the efficacy of adoptive T cell therapy in patient-derived tumor models. Therefore mitochondrial fission inhibition might provide an approach to enhance the efficacy of T cell-based immunotherapy.


Assuntos
Dinâmica Mitocondrial , Neoplasias , Animais , Endorribonucleases , Complexo Principal de Histocompatibilidade , Camundongos , Dinâmica Mitocondrial/fisiologia , Neoplasias/terapia , Proteínas Serina-Treonina Quinases
19.
Laryngoscope ; 131(5): 1157-1162, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32975857

RESUMO

OBJECTIVES/HYPOTHESIS: To evaluate the application and advantages of coblation tonsillectomy with inferior pole capsule preservation in pediatric patients with tonsillar hypertrophy and recurrent tonsillitis. STUDY DESIGN: Retrospective chart review. METHODS: A total of 726 children who were diagnosed with either tonsillar hypertrophy or recurrent tonsillitis were included. Children were divided into two groups according to the surgical technique: conventional coblation tonsillectomy and coblation tonsillectomy with inferior pole capsule preservation. The duration of surgery, intraoperative hemorrhage volume, and postoperative pain, as well as postoperative hemorrhage data in the format of time, location, and degree were compared between the two groups. RESULTS: Of the 726 children included, conventional coblation tonsillectomy was performed in 320 children, coblation tonsillectomy with inferior pole capsule preservation was performed in 406 children. There were no significant differences in duration of surgery or intraoperative hemorrhage volume between the two groups. Children who underwent coblation tonsillectomy with inferior pole capsule preservation showed a remarkable improvement in postoperative pain on days 3 and 5 postoperatively. Additionally, the coblation tonsillectomy with inferior pole capsule preservation group exhibited a significantly lower total postoperative hemorrhage rate, secondary hemorrhage rate, and hemorrhage rate in the inferior pole compared with that in the conventional coblation tonsillectomy group. During the 1-year follow-up period, no cases of tonsillar re-hypertrophy or recurrent tonsillitis were observed in either group. CONCLUSION: For pediatric tonsillar hypertrophy and recurrent tonsillitis, coblation tonsillectomy with inferior pole capsule preservation is a safe and effective technique, capable of reducing postoperative pain and hemorrhage, especially secondary hemorrhage at the inferior pole. LEVEL OF EVIDENCE: 3b Laryngoscope, 131:1157-1162, 2021.


Assuntos
Dor Pós-Operatória/diagnóstico , Tonsila Palatina/patologia , Hemorragia Pós-Operatória/epidemiologia , Tonsilectomia/métodos , Tonsilite/cirurgia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Hipertrofia/cirurgia , Masculino , Medição da Dor , Dor Pós-Operatória/etiologia , Tonsila Palatina/cirurgia , Hemorragia Pós-Operatória/etiologia , Recidiva , Estudos Retrospectivos , Tonsilectomia/efeitos adversos , Resultado do Tratamento
20.
Cell Death Dis ; 12(2): 144, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33542221

RESUMO

Abnormal expression of long-noncoding RNA is involved in the tumorigenesis and progression of various cancers, but the potential molecular regulatory mechanisms are unclear. Microbial flora and chronic inflammation, such as periodontitis, which is associated with oral cancer, affect the occurrence and progression of tumors. Accordingly, we stimulated the tongue squamous cell carcinoma (TSCC) cell lines CAL27 and SCC15 with a low concentration of lipopolysaccharide (LPS) from Porphyromonas gingivalis (P.g) for 6 days and then performed LncRNA sequencing on P.g-LPS-treated CAL27 cells and untreated CAL27 cells. LTSCCAT was upregulated in P.g-LPS-treated CAL27 cells compared with untreated CAL27 cells. LTSCCAT induced epithelial-mesenchymal transition and promoted the invasion and metastasis of TSCC in vitro and in vivo. LncRNA LTSCCAT was upregulated in TSCC patients with periodontitis and was correlated with metastasis and poor prognosis. We predicted through an online database and confirmed by dual-luciferase reporter assays that LTSCCAT is a competitive endogenous RNA for the regulation of miR-103a-2-5p. Another dual-luciferase reporter assay confirmed that miR-103a-2-5p has a binding site at the 3'-UTR of the histone methylation transferase SMYD3 and inhibits its translation. Chromatin immunoprecipitation experiments demonstrated that SMYD3 binds directly to the promoter region of TWIST1 and promotes its transcription, which is related to H3K4 trimethylation. The effect of pcDNA/LTSCCAT on expression was attenuated by miR-103a-2-5p mimics. The RF and SVM classifier predicts that LTSCCAT can bind to SMYD3, whereas the RNA immunoprecipitation (RIP) assay confirms that it cannot. In addition, we predicted the combination of LTSCCAT and SMYD3 through software, but the RIP assay confirmed that LTSCCAT could not be combined with SMYD3. For the first time, we showed that periodontitis promotes the invasion and metastasis of TSCC and clarified the molecular mechanism of LTSCCAT to promote invasion and metastasis of TSCC, providing a potential therapeutic target for clinical treatment of TSCC.


Assuntos
Histona-Lisina N-Metiltransferase/metabolismo , MicroRNAs/metabolismo , Proteínas Nucleares/metabolismo , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Neoplasias da Língua/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Feminino , Histona-Lisina N-Metiltransferase/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas Nucleares/genética , Periodontite/genética , Periodontite/metabolismo , Periodontite/patologia , Prognóstico , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias da Língua/genética , Neoplasias da Língua/patologia , Transfecção , Proteína 1 Relacionada a Twist/genética , Regulação para Cima
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