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1.
Heliyon ; 10(9): e30112, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38737287

RESUMO

Background: The reasons for gastrointestinal bleeding among patients with acquired immune deficiency syndrome (AIDS) were complex. Here we present an unusual case of life-threatening gastrointestinal bleeding caused by a cytomegalovirus-induced duodenal ulcer in an AIDS patient. Case presentation: A 31-year-old male with AIDS was admitted on July 18, 2023, complaining of abdominal pain for 38 days and intermittent hematochezia for 12 days. During his hospitalization, gastrointestinal endoscopy attributed gastrointestinal bleeding to a giant duodenal ulcer. Furthermore, cytomegalovirus(CMV) infection was confirmed as the reason for the ulcer through metagenomic next-generation sequencing (mNGs), hematoxylin-eosin(HE) staining, and immunohistochemistry (IHC) staining for the biopsy tissue. The patient's gastrointestinal bleeding was stopped by interventional embolization. Following a 4-week course of anti-CMV treatment, the giant duodenal ulcer was cured. Conclusions: For AIDS patients with gastrointestinal bleeding, the CMV-induced gastrointestinal ulcer should be considered. Comprehensive mothods (mNGs, HE staining and IHC staining for biopsy tissue) were benefit for confirmed diagnosis. Beside anti-CMV treatment, the interventional embolization is a choice for hemostasis.

2.
Molecules ; 29(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38474689

RESUMO

Hollow silica spheres have been widely studied for drug delivery because of their excellent biosecurity and high porosity. However, difficulties with degradation in the tumor microenvironment (TME) and premature leaking during drug delivery limit their clinical applications. To alleviate these problems, herein, hollow organosilica spheres (HOS) were initially prepared using a "selective etching strategy" and loaded with a photothermal drug: new indocyanine green (IR820). Then, the Cu2+-tannic acid complex (Cu-TA) was deposited on the surface of the HOS, and a new nanoplatform named HOS@IR820@Cu-TA (HICT) was finally obtained. The deposition of Cu-TA can gate the pores of HOS completely to prevent the leakage of IR820 and significantly enhance the loading capacity of HOS. Once in the mildly acidic TME, the HOS and outer Cu-TA decompose quickly in response, resulting in the release of Cu2+ and IR820. The released Cu2+ can react with the endogenous glutathione (GSH) to consume it and produce Cu+, leading to the enhanced production of highly toxic ·OH through a Fenton-like reaction due to the overexpressed H2O2 in the TME. Meanwhile, the ·OH generation was remarkably enhanced by the NIR light-responsive photothermal effect of IR820. These collective properties of HICT enable it to be a smart nanomedicine for dually enhanced chemodynamic therapy through GSH depletions and NIR light-triggered photothermal effects.


Assuntos
Complexos de Coordenação , Nanopartículas , Neoplasias , Polifenóis , Humanos , Peróxido de Hidrogênio , Sistemas de Liberação de Medicamentos , Glutationa , Microambiente Tumoral , Linhagem Celular Tumoral
4.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38493338

RESUMO

In recent years, there has been a growing trend in the realm of parallel clustering analysis for single-cell RNA-seq (scRNA) and single-cell Assay of Transposase Accessible Chromatin (scATAC) data. However, prevailing methods often treat these two data modalities as equals, neglecting the fact that the scRNA mode holds significantly richer information compared to the scATAC. This disregard hinders the model benefits from the insights derived from multiple modalities, compromising the overall clustering performance. To this end, we propose an effective multi-modal clustering model scEMC for parallel scRNA and Assay of Transposase Accessible Chromatin data. Concretely, we have devised a skip aggregation network to simultaneously learn global structural information among cells and integrate data from diverse modalities. To safeguard the quality of integrated cell representation against the influence stemming from sparse scATAC data, we connect the scRNA data with the aggregated representation via skip connection. Moreover, to effectively fit the real distribution of cells, we introduced a Zero Inflated Negative Binomial-based denoising autoencoder that accommodates corrupted data containing synthetic noise, concurrently integrating a joint optimization module that employs multiple losses. Extensive experiments serve to underscore the effectiveness of our model. This work contributes significantly to the ongoing exploration of cell subpopulations and tumor microenvironments, and the code of our work will be public at https://github.com/DayuHuu/scEMC.


Assuntos
Cromatina , RNA Citoplasmático Pequeno , Análise da Expressão Gênica de Célula Única , Análise por Conglomerados , Aprendizagem , RNA Citoplasmático Pequeno/genética , Transposases , Análise de Sequência de RNA , Perfilação da Expressão Gênica
5.
Nature ; 627(8004): 656-663, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38418883

RESUMO

Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies1. Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers. KRAS mutant cancer cells showed distinct transcriptional features, reduced differentiation and low levels of aneuploidy. Non-malignant areas surrounding human LUAD samples were enriched with alveolar intermediate cells that displayed elevated KRT8 expression (termed KRT8+ alveolar intermediate cells (KACs) here), reduced differentiation, increased plasticity and driver KRAS mutations. Expression profiles of KACs were enriched in lung precancer cells and in LUAD cells and signified poor survival. In mice exposed to tobacco carcinogen, KACs emerged before lung tumours and persisted for months after cessation of carcinogen exposure. Moreover, they acquired Kras mutations and conveyed sensitivity to targeted KRAS inhibition in KAC-enriched organoids derived from alveolar type 2 (AT2) cells. Last, lineage-labelling of AT2 cells or KRT8+ cells following carcinogen exposure showed that KACs are possible intermediates in AT2-to-tumour cell transformation. This study provides new insights into epithelial cell states at the root of LUAD development, and such states could harbour potential targets for prevention or intervention.


Assuntos
Adenocarcinoma de Pulmão , Diferenciação Celular , Células Epiteliais , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Aneuploidia , Carcinógenos/toxicidade , Células Epiteliais/classificação , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Organoides/efeitos dos fármacos , Organoides/metabolismo , Lesões Pré-Cancerosas/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Taxa de Sobrevida , Produtos do Tabaco/efeitos adversos , Produtos do Tabaco/toxicidade
6.
Small ; : e2311027, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263719

RESUMO

Nanozyme-based metabolic regulation triggered by tumor-specific endogenous stimuli has emerged as a promising therapeutic strategy for tumors. The current efficacy, however, is constrained by the limited concentration of endogenous substrates and the metabolic plasticity of tumors. Consequently, the implementation of efficient metabolic regulation in tumor therapy is urgently needed. Herein, a versatile nanozyme-based nicotinamide adenine dinucleotide (NADH) circulating oxidation nanoreactor is reported. First, the synthesized cobalt-doped hollow carbon spheres (Co-HCS) possess NADH oxidase (NOX)-mimicking activity for the NADH oxidation to disrupt oxidative phosphorylation (OXPHOS) pathway of tumor cells. Second, the substrate-cycle manner of Co-HCS can be used for NADH circulating oxidation to overcome the limitation of substrate deficiency. Finally, 2-Deoxy-D-glucose (2-DG) and 6-aminonicotinamide (6-AN) are introduced to block glycolysis and pentose phosphate pathway (PPP), thus creating a versatile nanozyme-based NADH circulating oxidation nanoreactor (Co-HCS/D/A) for tumor therapy through triple cellular metabolism disruption. In vitro and in vivo results demonstrate that the designed nanoreactor not only enhances the catalytic efficiency but also disrupts the tumor metabolic homeostasis, leading to efficient therapy outcome. This study develops a novel NADH circulating oxidation nanoreactor for tumor therapy through triple cellular metabolism disruption, which addresses the limitations of current nanozyme-based metabolism regulation for tumor therapy.

7.
J Hazard Mater ; 465: 133284, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38134699

RESUMO

The phosphate-mineralizing bacteria (PMBs) has shown great potential as a sustainable solution to support pollution remediation through its induced mineralization capacity. However, few studies have been conducted on the mechanism of cadmium (Cd) tolerance in PMBs. In this study, a PMB strain, Enterobacter sp. PMB-5, screened from Cd-contaminated rhizosphere soil, has high resistance to Cd (540 - 1220 mg/L) and solubilized phosphate (232.08 mg/L). The removal experiments showed that the strain PMB-5 removed 71.69-98.24% and 34.83-76.36% of Cd with and without biomineralization, respectively. The characterization result of SEM, EDS, TEM, XPS and XRD revealed that PMB-5 induced Cd to form amorphous phosphate precipitation through biomineralization and adopted different survival strategies, including biomineralization, bioaccumulation, and biosorption to resistance Cd in the microbial induced phosphate precipitation (MIPP) system and the non-MIPP system, respectively. Moreover, the results of whole genome sequencing and qRT-PCR indicated that phosphorus metabolism genes such as pst, pit, phn, ugp, ppk, etc. and heavy metal tolerance genes (including ion transport, ion efflux, redox, antioxidant stress), such as czcD, zntA, mgtA, mgtC, katE, SOD2, dsbA, cysM, etc. were molecular for the PMB-5 mineralization and Cd tolerance of PMB-5. Together, our findings suggested Enterobacter sp. PMB-5 is a potential target for developing more effective bioinoculants for Cd contamination remediation.


Assuntos
Enterobacter , Poluentes do Solo , Enterobacter/metabolismo , Cádmio/metabolismo , Biomineralização , Fosfatos , Bioacumulação , Poluentes do Solo/metabolismo , Solo
8.
BMC Infect Dis ; 23(1): 795, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37964230

RESUMO

BACKGROUND: A surge of more than 80 million Omicron variant infected cases was reported in China less than a month after the "zero COVID" strategy ended on December 7, 2022. In this circumstance, whether people living with HIV (PLWH) in China experience a similar risk is not clear. METHODS: A cross-sectional study was conducted in the Wuchang District of Wuhan between December 20, 2022, and January 18, 2023 through a self-administered online survey. PLWH and HIV-negative people aged ≥ 18 years old who volunteered for this survey were eligible. The prevalence of Omicron variant infection between PLWH and HIV-negative people was compared, and the factors associated with the Omicron variant infection among PLWH and HIV-negative people were further evaluated, respectively. RESULTS: In total, 890 PLWH and 1,364 HIV-negative adults from Wuchang District were enrolled. Among these participants, 690 PLWH (77.5%) and 1163 HIV-negative people (85.3%) reported SARS-CoV-2 infection. Gender, chronic disease conditions, and COVID-19 vaccination status significantly differed between the two groups. After adjusting gender, age, comorbidities, and COVID-19 vaccination status, the risk of SARS-CoV-2 infection among PLWH was significantly lower than among HIV-negative people (aOR 0.56, 95%CI 0.42-0.76). Multivariable logistic regression analysis showed that PLWH with older age and detectable HIV-viral load (HIV-VL) had decreased risk of SARS-CoV-2 infection (aOR 0.98, 95%CI 0.96-0.99; aOR 0.59, 95%CI 0.36-0.97). Compared with PLWH receiving one/two doses of COVID-19 vaccines, no significant differences in the risk of SARS-CoV-2 infection were observed among PLWH receiving three doses of inactivated vaccines and four doses of vaccines (three doses of inactivated vaccines plus one dose of inhaled recombinant adenovirus type 5 (AD5)-vectored vaccine). Among HIV-negative people, those receiving four doses of COVID-19 vaccines had a lower risk of SARS-CoV-2 infection than those receiving one/two doses (aOR 0.14, 95%CI 0.08-0.25). CONCLUSIONS: Our study proves that PLWH have a lower risk of Omicron variant infection than HIV-negative people. However, even PLWH with younger age and virological suppression should strengthen the prevention against SARS-CoV-2 infection. Three doses of inactivated vaccines plus one dose of inhaled recombinant AD5-vectored COVID-19 vaccine may provide better protection for HIV-negative people.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Humanos , Adolescente , Estudos Transversais , COVID-19/epidemiologia , China/epidemiologia , Vacinas de Produtos Inativados
9.
Am J Trop Med Hyg ; 109(6): 1274-1276, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-37972321

RESUMO

Oral ulcers are often neglected in patients with AIDS. However, giant oral ulcers are uncommon and are usually suspected to be malignant lesions. Our study presents a case of giant ulcers in an AIDS patient that were initially suspected to be oral cancer. To assist with diagnosis, conventional microbiological tests, metagenomic next-generation sequencing, and a pathological examination were conducted on oral lesion biopsy specimens. The case was finally confirmed via hematoxylin-eosin staining and immunohistochemical staining to be a cytomegalovirus infection.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por Citomegalovirus , Úlceras Orais , Humanos , Úlceras Orais/etiologia , Síndrome da Imunodeficiência Adquirida/complicações , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Coloração e Rotulagem
10.
Zhonghua Nan Ke Xue ; 29(1): 31-37, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-37846829

RESUMO

OBJECTIVE: To explore the clinical value of the inflammasomes NLRP1 and NLRC4 in the diagnosis and treatment of PCa. METHODS: Using immunohistochemical staining, we detected the expressions of the inflammasomes NLRP1 and NLRC4 and the inflammatory cytokines IL-18 and IL-1ß in 54 cases of BPH and 58 cases of PCa treated in Pinghu First People's Hospital from January 2022 to May 2022. We analyzed the characteristics of their expressions in the two groups of patients and the correlation of NLRP1 and NLRC4 expressions with tPSA, fPSA and Gleason scores in the PCa patients. Based on the Cancer Genome Atlas dataset, we compared the expressions of NLRP1 and NLRC4 in different stages of PCa. RESULTS: The NLRP1 and NLRC4 expressions were significantly increased in the PCa patients (P < 0.001). The expression of NLRP1 was linearly correlated with those of IL-1ß and IL-18 (P < 0.05), and so was the expression of NLRC4 with that of IL-18 (P < 0.05). The expressions of NLRP1 and NLRC4 were positively correlated with the Gleason scores of the PCa patients (P < 0.05), the former remarkably higher in T3 and T4 than in T1 (P > 0.05), and the latter markedly higher in T2, T3 and T4 than in T1 (P < 0.05). CONCLUSION: The inflammasomes NLRP1 and NLRC4 are highly expressed in PCa and facilitate tumorgenesis by promoting the maturation and release of the inflammatory cytokines IL-1ß and IL-18, which indicates their important role in the progression of tumors and clinical value in the risk assessment and prognosis of PCa.


Assuntos
Inflamassomos , Neoplasias da Próstata , Masculino , Humanos , Inflamassomos/metabolismo , Interleucina-18/metabolismo , Citocinas/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteínas NLR/metabolismo
11.
Oncol Lett ; 26(3): 385, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37559581

RESUMO

The present study explored the clinical value of the protein expression levels of nucleotide binding oligomerization-like receptor family pyrin domain containing 1 (NLRP1) and nucleotide-binding oligomerization domain leucine-rich repeat and caspase recruitment domain-containing 4 (NLRC4) inflammasomes in the diagnosis and treatment of prostate cancer. A total of 54 patients with prostatic hyperplasia and 58 patients with prostate cancer were recruited at The First People's Hospital of Pinghu between January and May 2022. Immunohistochemical staining was used to determine the protein expression levels of the NLRP1 and NLRC4 inflammasomes in addition to the proinflammatory cytokines IL-18 and IL-1ß in the two groups of patients. The protein expression levels of NLRP1 and NLRC4 inflammasome were significantly increased in patients with prostate cancer compared with patients with prostate hyperplasia. The differences in expression of NLRP1 and NLRC4 inflammatory vesicles in prostate cancer of different stages were also compared based on data from The Cancer Genome Atlas. The protein expression level of NLRP1 demonstrated a significant positive correlation with IL-1ß and IL-18 expression, and the protein expression level of the NLRC4 inflammasome was significantly positively correlated with IL-18 expression. The protein expression levels of both NLRP1 and NLRC4 demonstrated a significant positive correlation with the Gleason score of prostate cancer. The expression of NLRP1 in tumor (T)3/T4 was significantly higher compared with T1 and expression of the NLRC4 inflammasome in T2 and T3/T4 was significantly higher compared with T1. Expression of the NLRP1 and NLRC4 inflammasomes was significantly higher in patients with prostate cancer, compared with patients with prostatic hyperplasia. Therefore, expression of NLRP1 and NLRC4 may promote tumorigenesis by promoting the maturation and release of proinflammatory cytokines IL-1ß and IL-18. Expression of the NLRP1 and NLRC4 inflammasomes demonstrated a significant positive correlation with the risk of prostate cancer. Expression of the NLRP1 and NLRC4 inflammasomes in middle- and advanced-stage tumors was higher compared with early-stage tumors. These results suggested that inflammasome expression may serve a significant role in the progression of tumors and could provide a fixed value for the risk assessment and prognosis prediction of prostate cancer.

12.
Biomed Mater ; 18(5)2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37467765

RESUMO

As an emerging treatment method, photodynamic therapy (PDT) has attracted considerable interest due to the characteristics of non-invasiveness, repeatable treatment, high spatiotemporal resolution and few side effects. However, the life span (<40 ns) and diffusion distance (<20 nm) of reactive oxygen species such as singlet oxygen (1O2) in tumor cells are extremely short, which has seriously limited therapeutic efficacy of PDT. The enrichment site of photosensitizers in cancer cells is usually the first site of PDT action, which will not only affect the biological signaling pathway of cancer cell death, but also is closely related to the final therapeutic effect. Therefore, the design and preparation of photosensitizers targeting specific subcellular organelles can directly break the biological function of the organelle and trigger the corresponding cell death signaling pathway, which can significantly improve the efficacy of PDT. Herein, a lysosome-targeted silicon quantum dots (L-Si QDs) was first made by diethylene glycol-mediated synthetic route as a multicolor fluorescent imaging reagents and a new photosensitizer. The as-prepared L-Si QDs exhibit bright fluorescence with excellent pH stability and time stability, excitation-dependent emission, and good biocompatibility. Furthermore, the results of cell experiments showed that L-Si QDs was accumulated in lysosomes after being taken up by cancer cells, and can efficiently produce1O2upon 635 nm laser irradiation, which can damage lysosomes, up-regulate cleavage caspase-3, increase Bax release, down-regulate Bcl-2 and induce cell apoptosis finally. This study significantly broadens the biomedical applications of silicon quantum dots and provides excellent nanomaterials candidates for tumor phototherapy.


Assuntos
Neoplasias , Fotoquimioterapia , Pontos Quânticos , Humanos , Fármacos Fotossensibilizantes , Fotoquimioterapia/métodos , Silício , Medicina de Precisão , Neoplasias/tratamento farmacológico , Lisossomos
13.
Medicine (Baltimore) ; 102(30): e34349, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37505161

RESUMO

RATIONALE: Multiple primary malignant tumors are rare and challenging to diagnose. Diffuse malignant peritoneal mesothelioma (DMPM) originate from the peritoneum, which lacks specific clinical manifestations and is difficult to diagnose, with a short survival about 10 to 13 months for inoperable ones. This is the first report of metachronous double primary malignant tumors in nasopharyngeal carcinoma and DMPM accompanied with paraneoplastic syndromes. PATIENT CONCERNS: A 61-year-old man presented with abdominal discomfort with a history of nasopharyngeal carcinoma 5 years ago. DIAGNOSES: The diagnosis of DMPM was finally confirmed by laparoscopic mesenteric biopsies. Paraneoplastic syndromes including increased platelets were present when diagnosis, followed by increased neutrophils after disease progression. INTERVENTIONS: Due to intolerable for surgery, he was treated with pemetrexed combined with nivolumab, intraperitoneal infusion of nivolumab, radiotherapy, anlotinib and maintenance treatment of nivolumab. OUTCOMES: Progression-free survival in first line is 12 months, overall survival is 23 months. LESSONS: This indicate that comprehensive treatment including immunotherapy may be helpful for inoperable DMPM patients with nasopharyngeal carcinoma accompanied with paraneoplastic syndromes.


Assuntos
Mesotelioma Maligno , Mesotelioma , Neoplasias Nasofaríngeas , Síndromes Paraneoplásicas , Neoplasias Peritoneais , Masculino , Humanos , Pessoa de Meia-Idade , Peritônio/patologia , Nivolumabe/uso terapêutico , Mesotelioma/complicações , Mesotelioma/tratamento farmacológico , Carcinoma Nasofaríngeo , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/tratamento farmacológico , Síndromes Paraneoplásicas/etiologia , Neoplasias Nasofaríngeas/complicações , Neoplasias Nasofaríngeas/tratamento farmacológico
14.
Front Cell Infect Microbiol ; 13: 1162420, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37483385

RESUMO

Background: Currently the responses of peripheral cytokine-secreting cells in the natural course of human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection haven't been fully elucidated. Methods: The function of peripheral proinflammatory, regulatory and cytotoxic cytokine-secreting cells were investigated by direct intracellular cytokine staining (ICS) and flow cytometry, additionally, the absolute numbers of different cytokine-secreting cells were measured among patients with HIV/TB co-infection (HT group), and compared them with the healthy controls (HC group), patients with TB (TB group) and patients with HIV infection (HIV group). After one week's anti-TB treatment, the changes of the percentages of cytokine-secreting cells were further evaluated in TB and HT groups. Results: Totally 26 individuals in the HC group, 51 in the TB group, 26 in the HIV group and 29 in the HT group were enrolled. The HT. HT group exhibited significantly lower absolute numbers of IFN-γ+CD4+, IFN-γ+CD8+, TNF-α+CD4+, IL17A+CD4+ T cells and TNF-α+CD14+ monocytes than the TB and HIV groups. Compared with the TB group, the percentages of CD8+ T cells secreting IFN-γ and perforin (p=0.010; p=0.043) were significantly lower among the HT group. Compared with the HIV group, the percentages of CD4+, CD8+ T cells and CD14+ monocytes secreting TNF-α (p=0.013; p=0.001; p<0.001) were significantly decreased, and the percentage of CD8+ T cells secreting IL-17A (p=0.015) was significantly increased among the HT group. Both the percentages of CD4+ T cells secreting TGF-ß (p<0.001; p=0.001), and CD4+ and CD8+ T cells secreting granzyme A (all p<0.001), were significantly higher among the HT group than among the TB group and HIV group. After one week's anti-TB treatment, an increased percentage of CD4+ T cells secreting TNF-α (p=0.003) was found in the TB group, and an increased percentage of CD8+ T cells secreting TNF-α (p=0.029) was found in the HT group. Conclusion: Significantly different functional profiles of peripheral proinflammatory, regulatory, and cytotoxic cytokine-secreting cells were observed in the natural course of HIV/TB co-infection compared to TB and HIV infection alone, even though the absolute numbers of those cells were significantly lower in HIV/TB co-infection. TNF-α-secreting CD8+ T cells may be a more sensitive marker for early evaluation of anti-TB treatment efficacy in patients with HIV/TB co-infection.


Assuntos
Coinfecção , Infecções por HIV , Tuberculose Latente , Tuberculose , Humanos , Citocinas , Infecções por HIV/complicações , Linfócitos T CD8-Positivos , Fator de Necrose Tumoral alfa , Linfócitos T CD4-Positivos
15.
Adv Mater ; 35(44): e2305073, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37421648

RESUMO

Pyroptosis is increasingly considered a new weathervane in cancer immune therapy. However, triggering specific pyroptotic tumor cell death while preserving normal cells still remains a major challenge. Herein, a brand-new pyroptosis inducer, copper-bacteriochlorin nanosheet (Cu-TBB), is designed. The synthesized Cu-TBB can be activated to an "on" state in the tumor microenvironment with glutathione (GSH) overexpression, leading to the release of Cu+ and TBB, respectively. Intriguingly, the released Cu+ can drive cascade reactions to produce O2 -• and highly toxic ·OH in cells. Additionally, the released TBB can also generate O2 -• and 1 O2 upon 750 nm laser irradiation. Encouragingly, both Cu+ -driven cascade reactions and photodynamic therapy pathways result in potent pyroptosis along with dendritic cell maturation and T cell priming, thus simultaneously eliminating the primary tumors and inhibiting the distant tumor growth and metastases. Conclusively, the well-designed Cu-TBB nanosheet is shown to trigger specific pyroptosis in vitro and in vivo, leading to enhanced tumor immunogenicity and antitumor efficacy while minimizing systemic side effects.


Assuntos
Neoplasias , Porfirinas , Humanos , Piroptose , Cobre , Imunoterapia , Glutationa , Microambiente Tumoral , Linhagem Celular Tumoral , Neoplasias/terapia
16.
Brief Bioinform ; 24(4)2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37280190

RESUMO

Clustering methods have been widely used in single-cell RNA-seq data for investigating tumor heterogeneity. Since traditional clustering methods fail to capture the high-dimension methods, deep clustering methods have drawn increasing attention these years due to their promising strengths on the task. However, existing methods consider either the attribute information of each cell or the structure information between different cells. In other words, they cannot sufficiently make use of all of this information simultaneously. To this end, we propose a novel single-cell deep fusion clustering model, which contains two modules, i.e. an attributed feature clustering module and a structure-attention feature clustering module. More concretely, two elegantly designed autoencoders are built to handle both features regardless of their data types. Experiments have demonstrated the validity of the proposed approach, showing that it is efficient to fuse attributes, structure, and attention information on single-cell RNA-seq data. This work will be further beneficial for investigating cell subpopulations and tumor microenvironment. The Python implementation of our work is now freely available at https://github.com/DayuHuu/scDFC.


Assuntos
Algoritmos , Análise da Expressão Gênica de Célula Única , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Análise por Conglomerados , Perfilação da Expressão Gênica/métodos
17.
Environ Sci Pollut Res Int ; 30(32): 78408-78422, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37269515

RESUMO

In this study, the capacity of cadmium (Cd)-resistant plant growth-promoting bacteria (PGPB) Burkholderia sp. SRB-1 (SRB-1) and its mechanisms were explored through morphological characterizations, biochemical response, plant growth-promoting traits, and functional gene expression patterns. The results showed that SRB-1 was an excellent Cd-resistant bacteria (MIC was 420 mg L-1), and its maximum Cd removal rate reached 72.25%. Biosorption was the main removal method of Cd for SRB-1, preventing intracellular Cd accumulation and maintaining cellular metabolism. Various functional groups on the cell wall were involved in Cd binding, which deposited as CdS and CdCO3 on the cell surface according to XPS analysis and might be critical for reducing Cd physiochemical toxicity. Furthermore, metals exporting (zntA, czcA, czcB, czcC), detoxification (dsbA, cysM), and antioxidation (katE, katG, SOD1) related genes were annotated in the SRB-1 genome. The results of Cd distribution and antioxidative enzyme activity in SRB-1 also illustrated that Cd2+ efflux and antioxidative response were the main intracellular Cd-resistant mechanisms. These conclusions were further verified by qRT-PCR analysis. Overall, the strategies of extracellular biosorption, cation efflux, and intracellular detoxification jointly build the Cd-resistant system, which invested Burkholderia sp. SRB-1 with potential for bioremediation in heavily Cd-contaminated environmental sites.


Assuntos
Burkholderia , Poluentes do Solo , Cádmio/análise , Burkholderia/metabolismo , Biodegradação Ambiental , Poluentes do Solo/análise
18.
Sensors (Basel) ; 23(9)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37177699

RESUMO

Surgical skill assessment can quantify the quality of the surgical operation via the motion state of the surgical instrument tip (SIT), which is considered one of the effective primary means by which to improve the accuracy of surgical operation. Traditional methods have displayed promising results in skill assessment. However, this success is predicated on the SIT sensors, making these approaches impractical when employing the minimally invasive surgical robot with such a tiny end size. To address the assessment issue regarding the operation quality of robot-assisted minimally invasive surgery (RAMIS), this paper proposes a new automatic framework for assessing surgical skills based on visual motion tracking and deep learning. The new method innovatively combines vision and kinematics. The kernel correlation filter (KCF) is introduced in order to obtain the key motion signals of the SIT and classify them by using the residual neural network (ResNet), realizing automated skill assessment in RAMIS. To verify its effectiveness and accuracy, the proposed method is applied to the public minimally invasive surgical robot dataset, the JIGSAWS. The results show that the method based on visual motion tracking technology and a deep neural network model can effectively and accurately assess the skill of robot-assisted surgery in near real-time. In a fairly short computational processing time of 3 to 5 s, the average accuracy of the assessment method is 92.04% and 84.80% in distinguishing two and three skill levels. This study makes an important contribution to the safe and high-quality development of RAMIS.


Assuntos
Robótica , Competência Clínica , Redes Neurais de Computação , Movimento (Física) , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
19.
Front Oncol ; 13: 1037156, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37064145

RESUMO

Rationale: Primary renal parenchymal squamous cell carcinoma (SCC) is an extremely rare tumor that is difficult to diagnose by hematology and imaging studies and is often diagnosed later than other primary renal cancers. Diagnosis: A 52-year-old male patient was found to have cysts in both kidneys for 1 week. No urgency and frequency of urination, no dysuria, no gross hematuria, and no significant changes in recent body weight were reported. Interventions: The upper pole of the right kidney is a cystic and solid mass (8.3 cm * 8.2 cm * 8.1 cm), the cystic part has long T1 and long T2 signals, the solid part has mixed signals, and some parts have limited diffusion. There were nodular long T1 and short T2 calcification signals. An enhanced scan of the solid part showed uneven enhancement and continuous enhancement of the mass capsule. Cystic renal cancer was considered because of the multiple cysts in both kidneys. Surgical treatment was performed. Postoperative pathology revealed well-differentiated squamous cell carcinoma of the right kidney with cystic degeneration, 8.5 cm * 6 cm in size, infiltrating the renal parenchyma, and the cutting edge was negative. The pathological stage was pT2bN0M0. Outcome: At the follow-up 5 months after the operation, no metastasis was found. Conclusion: Renal SCC is rare and easily misdiagnosed and missed. Pathological diagnosis is still the gold standard for its diagnosis. However, with active surgical treatment, the short-term prognosis of the patient is good.

20.
Quant Imaging Med Surg ; 13(4): 2426-2440, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37064370

RESUMO

Background: The sensitivity and correlation of coronary computed tomography angiography (CTA) as compared with histopathology are unknown in evaluating coronary arterial calcification. In this study, we retrospectively evaluated qualitatively and quantitatively the sensitivity and correlation of coronary CTA compared with histopathology in assessing coronary arterial calcification. Methods: This study was conducted on 12 randomly selected cadavers aged over 40 years at the time of death, and 53 segments of coronary arteries from these 12 cadavers were obtained from the Human Anatomy Laboratory of Tianjin Medical University. The artery segments were scanned using contrasted-enhanced dual-source computed tomography (DSCT) with an axial slice thickness of 0.6 mm. Coronary artery calcification in a coronary segment was defined as the presence of 1 or more voxels with a CT density >130 Hounsfield units. According to the arc of calcification in the cross section of the coronary artery wall, calcified plaques were divided into three categories: mild, moderate, and severe calcification. The coronary artery stenosis caused by calcified plaque was observed and calculated with multiplanar reconstruction (MPR), maximum density projection, volume rendering (VR), and cross-sectional reconstruction. After CT enhancement scanning, the coronary artery specimens were cut into 4-mm long segments and embedded in paraffin for pathological staining. Pathological classification and coronary artery stenosis measured with pathological analysis were used as comparison criteria. Results: Histopathology detected 69 Vb-type plaques, while DSCT detected 57 calcified plaques. The sensitivity of CT for detecting mild, moderate, and severe calcified plaques were 88.3% [95% confidence interval (CI): 74.1-95.6%], 100% (95% CI: 69.8-100%), and 100% (95% CI: 73.2-100%), respectively. DSCT had a significant (P<0.001) correlation with histopathology in quantifying coronary artery stenosis caused by mild, moderate, and severe calcified plaques (R2=0.9278, R2=0.9158, R2=0.7923, respectively). Compared with histopathology, DSCT overestimated coronary artery stenosis caused by mild, moderate, and severe calcified plaques (3.2%±2.0%, 4.9%±4.7%, and 14.7%±8.2%, respectively; P<0.05). Conclusions: DSCT contrast enhancement scanning can detect and characterize coronary artery calcification with a good correlation with histopathologic quantification of coronary artery stenosis caused by different types of calcified plaques, even though coronary CTA may overestimate the stenosis.

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