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1.
Transl Res ; 265: 26-35, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37914149

RESUMO

Lynch syndrome, an autosomal dominant hereditary disease arising from mutations in mismatch repair genes, is linked to the development of multiple tumor types, notably colorectal cancer, endometrial carcinoma and upper urinary tract urothelial carcinoma. In this study, we present the case of a young patient diagnosed with upper urinary tract urothelial carcinoma, notable for a familial history of diverse malignancies. By employing genetic analysis, we verified the presence of Lynch syndrome within the family and detected novel variants, MSH2 p.A604D and TSC2 p.C738Y, utilizing NGS technology. Subsequently, we conducted validation experiments to assess the pathogenicity of the MSH2 and TSC2 variants. We illustrated that the MSH2 variant can result in diminished MSH2 expression, compromised mismatch repair function, and induce resistance to cisplatin in urothelial carcinoma. Furthermore, we substantiated the promotional impact of the identified TSC2 variant on urothelial carcinoma, encompassing proliferation, invasion, and migration. Significantly, we found that the MSH2 p.A604D variant and TSC2 p.C738Y variant synergistically enhance the promotion of urothelial carcinoma.


Assuntos
Carcinoma de Células de Transição , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Renais , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/genética , China , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Proteína 2 Homóloga a MutS/genética , Neoplasias da Bexiga Urinária/genética
2.
Front Pharmacol ; 14: 1271252, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026987

RESUMO

Leukemia encompasses a group of highly heterogeneous diseases that pose a serious threat to human health. The long-term outcome of patients with leukemia still needs to be improved and new effective therapeutic strategies continue to be an unmet clinical need. Shikonin (SHK) is a naphthoquinone derivative that shows multiple biological function includes anti-tumor, anti-inflammatory, and anti-allergic effects. Numerous studies have reported the anti-leukemia activity of SHK during the last 3 decades and there are studies showing that SHK is particularly effective towards various leukemia cells compared to solid tumors. In this review, we will discuss the anti-leukemia effect of SHK and summarize the underlying mechanisms. Therefore, SHK may be a promising agent to be developed as an anti-leukemia drug.

3.
Front Microbiol ; 13: 989879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304945

RESUMO

China experienced another widespread Coronavirus disease 2019 (COVID-19) outbreak recently caused by the Omicron variant, which is less severe but far more contagious than the other COVID-19 variants, leading local governments to focus efforts on eliminating the spread of the disease. Previous studies showed that after "recovering" from the virus, some patients could re-test positive for COVID-19 with nucleic acid tests, challenging the control of disease spread. In this study, we aimed to analyze the clinical and laboratory characteristics of re-positive COVID-19 patients in Northeast China. We retrospectively analyzed data from confirmed reverse transcription polymerase chain reaction (RT-PCR) re-positive COVID-19 patients who were admitted to the First Hospital of Jilin University, Jilin Province, China, from March to June 2022. Detailed clinical symptoms, medical history, anti-Corona Virus (CoV) IgG and IgM levels, and CoV nucleic acid cycle threshold (Ct) values during the re-positive period were collected and analyzed. A total of 180 patients were included in this study, including 62 asymptomatic cases and 118 mild cases. The cohort included 113 men and 67 women, with an average age of 45.73 years. The median time between recovery from the virus and re-positivity was 13 days. Our results showed that the proportion of re-positive patients with symptoms was lower, and the nucleic acid test-positive duration was shorter during the re-positive period. Furthermore, in patients with underlying disease, the proportion of patients with symptoms was higher, anti-CoV IgG levels were lower, and the total disease duration was longer. In conclusion, during the re-positive period, the symptoms were milder, and the CoV nucleic acid test-positive course was shorter. The concomitant underlying disease is an important factor associated with clinical symptoms, and the overall course of COVID-19 re-positive patients may be associated with lower anti-CoV IgG levels. Large-scale and multicenter studies are recommended to better understand the pathophysiology of recurrence in patients with COVID-19.

4.
Transl Cancer Res ; 10(11): 4979-4987, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35116348

RESUMO

Pelvic malignant solitary fibrous tumor (SFT) is a relatively rare disease, and literature on radical resection with transcatheter arterial embolization of pelvic SFT is lacking. In this work, we report on a 55-year-old man with a presacral mass who was hospitalized at our department. Computed tomography and magnetic resonance imaging indicated pelvic space-occupying lesions that were 12 cm × 10 cm in size and pelvic lesions that were not clearly demarcated from the right posterior wall of the bladder and the right ureter. This result suggested severe secondary hydronephrosis of the right renal pelvis. The patient underwent transcatheter iliac arterial embolization. Radical tumor resection was performed, and the results of pathological examination confirmed the diagnosis of malignant pelvic SFT. There was no SFT recurrence in this patient at 1-year follow-up. Herein, we report on the treatment of a patient with malignant pelvic SFT, a rare condition, who underwent successful radical resection after transcatheter arterial embolization. Transcatheter arterial embolization can block the blood supply of the SFT as much as possible and improve the possibility of tumor resection. In the future, pelvic SFTs can be considered improving the resection rate by transcatheter arterial embolization before surgery.

5.
Proc Natl Acad Sci U S A ; 117(33): 20254-20264, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32747543

RESUMO

Correlated activation of cortical neurons often occurs in the brain and repetitive correlated neuronal firing could cause long-term modifications of synaptic efficacy and intrinsic excitability. We found that repetitive optogenetic activation of neuronal populations in the mouse cortex caused enhancement of optogenetically evoked firing of local coactivated neurons as well as distant cortical neurons in both ipsilateral and contralateral hemispheres. This global enhancement of evoked responses required coactivation of a sufficiently large population of neurons either within one cortical area or distributed in several areas. Enhancement of neuronal firing was saturable after repeated episodes of coactivation, diminished by inhibition of N-methyl-d-aspartic acid receptors, and accompanied by elevated excitatory postsynaptic potentials, all consistent with activity-induced synaptic potentiation. Chemogenetic inhibition of neuronal activity of the thalamus decreased the enhancement effect, suggesting thalamic involvement. Thus, correlated excitation of large neuronal populations leads to global enhancement of neuronal excitability.


Assuntos
Potenciais de Ação/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Excitabilidade Cortical , Corantes Fluorescentes , Masculino , Camundongos , Rede Nervosa , Transmissão Sináptica/fisiologia
6.
Mol Cell Biol ; 32(7): 1226-36, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22290433

RESUMO

SIRT1, a highly conserved NAD(+)-dependent protein deacetylase, is a key metabolic sensor that directly links nutrient signals to animal metabolic homeostasis. Although SIRT1 has been implicated in a number of hepatic metabolic processes, the mechanisms by which hepatic SIRT1 modulates bile acid metabolism are still not well understood. Here we report that deletion of hepatic SIRT1 reduces the expression of farnesoid X receptor (FXR), a nuclear receptor that regulates bile acid homeostasis. We provide evidence that SIRT1 regulates the expression of FXR through hepatocyte nuclear factor 1α (HNF1α). SIRT1 deficiency in hepatocytes leads to decreased binding of HNF1α to the FXR promoter. Furthermore, we show that hepatocyte-specific deletion of SIRT1 leads to derangements in bile acid metabolism, predisposing the mice to development of cholesterol gallstones on a lithogenic diet. Taken together, our findings indicate that SIRT1 plays a vital role in the regulation of hepatic bile acid homeostasis through the HNF1α/FXR signaling pathway.


Assuntos
Colesterol/metabolismo , Cálculos Biliares/metabolismo , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Fígado/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Sirtuína 1/genética , Animais , Deleção de Genes , Regulação da Expressão Gênica , Células HEK293 , Humanos , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , Receptores Citoplasmáticos e Nucleares/genética , Transdução de Sinais , Sirtuína 1/metabolismo
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