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The ß3-adrenoceptor is a protein responsible for regulating the body's response to the neurotransmitter adrenaline and the hormone norepinephrine. It is critical in various physiological processes, including metabolism, thermogenesis, and cardiovascular function. Recently, researchers have discovered that the ß3-adrenoceptor is also implicated in tumor progression and metastasis. Infections caused by Salmonella can lead to gastroenteritis; however, intriguingly, Salmonella is associated with tumor inhibition. In this study, Salmonella treatment resulted in the downregulation of ß3-adrenoceptor expression and a decrease in the phosphorylation of the Protein Kinase-B (AKT)/Mammalian Target of Rapamycin (mTOR) pathway, as observed through immunoblotting in a dose-dependent manner. Notably, Salmonella treatment significantly reduced tumor cell migration, as demonstrated by wound healing and Transwell assays. Moreover, tumor-bearing mice that received Salmonella-pre-treated tumor cells exhibited improved survival rates compared to those injected with tumor cells without prior Salmonella treatment. The observed anti-metastatic effect in this study suggests that Salmonella treatment could hold promise as a potential therapeutic approach to combat tumor metastasis. Further research is warranted to explore its full therapeutic potential.
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Phenols, ubiquitous environmental contaminants found in water, soil, and air, pose risks to organisms even at minimal concentrations, and many are classified as hazardous pollutants. Skin pigmentation is a natural shield against ultraviolet-induced DNA damage and oxidative stress, pivotal in reducing skin cancer incidences. Studies on B16F10 melanoma cells and zebrafish offer valuable insights into potential therapeutic avenues for melanoma in the context of phenol exposure. Upon phenol treatment, there was a marked decrease in melanin content and melanogenesis-associated protein expression, such as tyrosinase and the microphthalmia-associated transcription factor (MITF) in these melanoma cells. Additionally, phenols led to diminished p38 phosphorylation, amplified extracellular signal-regulated kinase (ERK) phosphorylation, and curtailed melanin expression in zebrafish. These observations underscore the detrimental impact of phenols on melanogenesis and propose a mechanism of action centered on the ERK/p38 signaling pathway. Consequently, our data spotlight the adverse effects of phenols on melanogenesis."
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Melanoma , Poluentes Químicos da Água , Animais , Melaninas/metabolismo , Peixe-Zebra/metabolismo , Melanogênese , Fenóis/toxicidade , Fenol , Poluentes Químicos da Água/toxicidade , Monofenol Mono-Oxigenase , Linhagem Celular TumoralRESUMO
Epithelial cell adhesion molecules (EpCAM) are highly expressed in many carcinomas and regulate the epithelial-mesenchymal transition, which is required for tumor metastasis. Furthermore, EpCAM overexpression induces tumor cells to develop a stem cell-like phenotype and promotes tumor progression. Targeting EpCAM may be a promising approach for inhibiting tumor metastasis and progression. Salmonella treatment suppresses tumor growth and reduces metastatic nodules in tumor-bearing mice. Based on these results, we hypothesized that Salmonella-based treatments could inhibit the expression of metastasis-associated proteins. The dose-dependent Salmonella treatment significantly downregulated the levels of EpCAM and decreased the phosphorylation of protein kinase-B (AKT)/mTOR (mammalian target of rapamycin) pathway, as shown by immunoblotting. In addition, Salmonella treatment increased the levels of epithelial markers and decreased the levels of mesenchymal markers in a dose-dependent manner. Wound-healing and Transwell assays showed that Salmonella treatment significantly reduced tumor cell migration. The mice were intravenously injected with B16F10 and CT26 cells pre-incubated with or without Salmonella, and the survival of tumor-bearing mice in the Salmonella group increased, indicating an antimetastatic effect. Our findings demonstrate that Salmonella plays a role in inhibiting tumor metastasis by downregulating EpCAM via the AKT/mTOR signaling pathway and has great potential for cancer therapy.
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Proteínas Proto-Oncogênicas c-akt , Sirolimo , Animais , Camundongos , Molécula de Adesão da Célula Epitelial/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sirolimo/farmacologia , Linhagem Celular Tumoral , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismo , Salmonella , Transição Epitelial-Mesenquimal , Movimento Celular , Proliferação de Células/genética , Mamíferos/metabolismoRESUMO
The imbalance of mucosal immunity in the lower gastrointestinal tract can lead to chronic inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis. IBD is a chronic inflammatory disorder that causes small and/or large intestines ulceration. According to previous studies, recombinant interleukin (IL)-10 protein and genetically modified bacteria secreting IL-10 ameliorate dextran sulfate sodium (DSS)-induced colitis in mice. IL-19 is a transcriptional activator of IL-10 and can alter the balance of T helper 1 (Th)1/Th2 cells in favor of Th2. In this study, we aimed to investigate whether the expression of the murine IL-19 gene carried by Salmonella choleraesuis (S. choleraesuis) could ameliorate murine IBD. Our results showed that the attenuated S. choleraesuis could carry and express the IL-19 gene-containing plasmid for IBD gene therapy by reducing the mortality and clinical signs in DSS-induced acute colitis mice as compared to the untreated ones. We also found that IL-10 expression was induced in IL-19-treated colitis mice and prevented inflammatory infiltrates and proinflammatory cytokine expression in these mice. We suggest that S. choleraesuis encoding IL-19 provides a new strategy for treating IBD in the future.
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Chondrosarcomas are primary cancers of cartilaginous tissue and capable of alteration to highly aggressive, metastatic, and treatment-refractory states, leading to a poor prognosis with a five-year survival rate at 11 months for dedifferentiated subtype. At present, the surgical resection of chondrosarcoma is the only effective treatment, and no other treatment options including targeted therapies, conventional chemotherapies, or immunotherapies are available for these patients. Here, we identify a signal pathway way involving EZH2/SULF1/cMET axis that contributes to malignancy of chondrosarcoma and provides a potential therapeutic option for the disease. A non-biased chromatin immunoprecipitation sequence, cDNA microarray analysis, and validation of chondrosarcoma cell lines identified sulfatase 1 (SULF1) as the top EZH2-targeted gene to regulate chondrosarcoma progression. Overexpressed EZH2 resulted in downregulation of SULF1 in chondrosarcoma cell lines, which in turn activated cMET pathway. Pharmaceutical inhibition of cMET or genetically silenced cMET pathway significantly retards the chondrosarcoma growth and extends mice survival. The regulation of EZH2/SULF1/cMET axis were further validated in patient samples with chondrosarcoma. The results not only established a signal pathway promoting malignancy of chondrosarcoma but also provided a therapeutic potential for further development of effective target therapy to treat chondrosarcoma.
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Neoplasias Ósseas , Condrossarcoma , Proteína Potenciadora do Homólogo 2 de Zeste , Sulfotransferases , Animais , Camundongos , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Cartilagem/patologia , Condrossarcoma/genética , Condrossarcoma/metabolismo , Condrossarcoma/patologia , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais , Sulfotransferases/genética , Humanos , Proteína Potenciadora do Homólogo 2 de Zeste/genéticaRESUMO
Robust antimicrobial coatings featuring high transparency, strong bactericidal activity, and an easy application procedure on generic surfaces can be widely accepted by the public to prevent pandemics. In this work, we demonstrated the hand-sprayer-based approach to deposit complex oxide coatings composed of Co-Mn-Cu-Zn-Ag on screen protectors of smartphones through acidic redox-assisted deposition (ARD). The as-obtained coatings possess high transparency (99.74% transmittance at 550 nm) and long-lasting durability against swiping (for 135 days of average use) or wet cleaning (for a routine of 3 times/day for 33 days). The spray coating enabling 3.14% Escherichia coli viability can further be reduced to 0.21% through a consistent elemental composition achieved via the immersion method. The high intake of Cu2+ in the coating is majorly responsible for the bactericidal activity, and the presence of Ag+ and Zn2+ is necessary to achieve almost complete eradication. The success of extending the bactericidal coatings on other typical hand-touched surfaces (e.g., stainless steel railings, rubber handrails, and plastic switches) in public areas has been demonstrated.
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Antibacterianos , Anti-Infecciosos , Antibacterianos/farmacologia , Aço Inoxidável , Escherichia coli , ÓxidosRESUMO
Thyroid cancer has been known as the most common endocrine malignancy. Although majority of thyroid cancer types respond well to conventional treatment including surgery and radioactive iodine therapy, about 10% of those with differentiated thyroid cancer will present distant metastasis and will have persistent or recurrent disease. Even more serious is a rare type of thyroid cancer called anaplastic thyroid cancer (ATC), which accounts for about 1%, has been demonstrated as the most lethal and aggressive form of human malignancy. Unfortunately, these tumors are also frequently resistant to traditional therapy. Previous study have shown that Salmonella inhibits tumor growth, in part, by inducing autophagy - a cellular process that is important in the innate and adaptive immunity in response to viral or bacterial infection. In our study, we intended to investigate whether Salmonella can inhibit tumor growth by inducing autophagy, specifically in thyroid cancer and elucidate the possible molecular mechanism. In order to determine the signaling pathway involved in tumor cell autophagy, we used Salmonella to treat ATC cells line ASH-3 and KMH-2 in vitro. The autophagic markers, particularly autophagy-related gene 6 (Beclin-1), microtubule-associated protein 1A/1B-light chain 3 (LC3) and p62, were observed to be differentially expressed after infection with Salmonella indicating an activated autophagy in ATC cells. In addition, the protein expression levels of phospho-protein kinase B (P-AKT), phospho-mammalian targets of rapamycin (P-mTOR), phospho-p70 ribosomal s6 kinase (P-p70S6K) in tumor cells were decreased after Salmonella infection. In vivo, we also found that substantial cell numbers of Salmonella targeted tumor tissue, and regulated anti-tumor mechanisms. Our findings showed that Salmonella activated autophagic signaling pathway and inhibited ATC tumor growth via downregulation of AKT/mTOR pathway.
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Chemotherapy is a treatment method commonly used for cancer and that patients showing low to no response to the treatment often developed drug resistance via multiple mechanisms. Natural products have been shown to reduce tumor drug resistance. Hinokitiol, a natural tropolone derivative, has potential as an antitumor agent. To improve the efficacy and safety of hinokitiol, a further understanding of hinokitiol interactions with the tumor microenvironment is necessary. The presence of plasma membrane multidrug resistance protein P-glycoprotein (P-gp) is favorable for tumor cells to elicit chemotherapeutic resistance. Here, we showed that hinokitiol dose-dependently decreased P-gp expression and suppressed the P-gp-driven efflux activity based on Rhodamine 123 assay. The protein expression levels of phosph-protein kinase B (P-AKT), phosph-mammalian targets of rapamycin (P-mTOR), and phosph-p70 ribosomal s6 kinase (P-p70s6K) in tumor cells were likewise reduced after hinokitiol treatment. The transfection of cells with active P-AKT rescued hinokitiol-induced downregulation of P-gp, suggesting the involvement of Akt/mTOR/p70s6K signaling in P-gp expression. Our results showed that hinokitiol can chemosensitize cancer cells. These findings indicate that hinokitiol could enhance 5-Fluorouracil therapeutic effects in murine B16F10 and CT26 tumor cells via downregulation of the AKT/mTOR pathway.
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Bacteria-mediated cancer therapy (BMCT) is an emerging tool that may advance potential approaches in cancer immunotherapy, whereby tumors are eradicated by the hosts' immune system upon recruitment and activation by bacteria such as Salmonella. This paper provides an emphasis on the immunomodulatory effects that encompasses both the innate and adaptive immune responses inherently triggered by Salmonella. Furthermore, modifications of Salmonella-based treatment in the attempt to improve tumor-specific immune responses including cytokine therapy, gene therapy, and DNA vaccine delivery are likewise discussed. The majority of the findings described herein incorporate cell-based experiments and murine model studies, and only a few accounts describe clinical trials. Salmonella-based cancer therapy is still under development; nonetheless, the pre-clinical research and early-phase clinical trials that have been completed so far have shown promising and convincing results. Certainly, the continuous development of, and innovation on, Salmonella-based therapy could pave the way for its eventual emergence as one of the mainstream therapeutic interventions addressing various types of cancer.
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Coronavirus Disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the global challenge. Reaching global herd immunity will help end the COVID-19 pandemic. However, vaccine shortage and vaccine hesitancy are the obstacles to achieve global herd immunity against SARS-CoV-2. The current homologous vaccine regimen is experimentally switching to heterologous vaccination at several study sites. However, the reactogenicity of heterologous ChAdOx1-S and mRNA vaccination against SARS-CoV-2 is still unclear. We have conducted a systematic review to summarize the current findings on the safety and immunogenicity of this heterologous vaccination and elucidate their implications against SARS-CoV-2. This systematic review was conducted by the guidelines of PRISMA. Articles were searched from PubMed and other sources (MedRixv and Google scholar) starting from 1 January to 5 September 2021. The search term was heterologous ChAdOx1-S and BNT162b2 or mRNA-1273 vaccination. Our review found that participants with ChAdOx1/BNT162b2, ChAdOx1-S/mRNA-1273 or BNT162b2/ChAdOx1-S did not have the serious adverse events seen with homologous vaccination. Participants with the heterologous regimen (ChAdOx1/BNT162b2, ChAdOx1-S/mRNA-1273 or BNT162b2/ChAdOx1-S), compared with those with two doses of ChAdOx1-S, have shown a more robust immune responses against SARS-CoV-2, such as higher levels of responsive antibodies or increased numbers of spike-specific T-cells. Nevertheless, these immune responses were slightly diminished in the recipients of BNT162b2/ChAdOx1-S. Also, the safety study of heterologous ChAdOx1-S/mRNA vaccination was based on small populations. Further studies to enclose diverse categories, such as race/ethnicity or geography, may be necessary. Overall, the heterologous immunization with ChAdOX1-S and the mRNA vaccine may improve the vaccine shortage related slow pace of reaching herd immunity, especially using the heterologous immunization with ChAdOx1-S/BNT162b2.
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During the coronavirus disease 2019 (COVID-19) pandemic, several case studies demonstrated that many asymptomatic patients with COVID-19 underwent fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) examination for various indications. However, there is a lack of literature to characterize the pattern of [18F]FDG PET/CT imaging on asymptomatic COVID-19 patients. Therefore, a systematic review to analyze the pulmonary findings of [18F]FDG PET/CT on asymptomatic COVID-19 patients was conducted. This systematic review was performed under the guidelines of PRISMA. PubMed, Medline, and Web of Science were used to search for articles for this review. Articles with the key words: "asymptomatic", "COVID-19", "[18F]FDG PET/CT", and "nuclear medicine" were searched for from 1 January 2020 to 20 May 2021. Thirty asymptomatic patients with COVID-19 were included in the eighteen articles. These patients had a mean age of 62.25 ± 14.85 years (male: 67.71 ± 12.00; female: 56.79 ± 15.81). [18F]FDG-avid lung lesions were found in 93.33% (28/30) of total patients. The major lesion was [18F]FDG-avid multiple ground-glass opacities (GGOs) in the peripheral or subpleural region in bilateral lungs, followed by the consolidation. The intensity of [18F]FDG uptake in multiple GGOs was 5.605 ± 2.914 (range from 2 to 12) for maximal standardized uptake value (SUVmax). [18F]FDG-avid thoracic lymph nodes (LN) were observed in 40% (12/40) of the patients. They mostly appeared in both mediastinal and hilar regions with an SUVmax of 5.8 ± 2.93 (range from 2.5 to 9.6). The [18F]FDG uptake was observed in multiple GGOs, as well as in the mediastinal and hilar LNs. These are common patterns in PET/CT of asymptomatic patients with COVID-19.
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Tumor metastasis is the main reason for the death of most cancer patients. C-X-C chemokine receptor type 4 (CXCR4) has been demonstrated to be overexpressed in numerous types of cancer. CXCR4 selectively binds with stromal cell-derived factor 1 (SDF1), also known as C-X-C family chemokine ligand 12 (CXCL12) (CXCL12/SDF-1), which induced tumor proliferation and metastasis. Recently, the use of conventional cancer treatments had some limitation; bacteria treatment for cancer becomes a trend that overcomes these limitations. Plenty of studies show that Salmonella has anti-tumor and anti-metastatic activity. The current study aimed to investigate Salmonella suppresses CXCR4 protein expression and tumor cell migration ability in B16F10 melanoma and LL2 lung carcinoma cells. Salmonella reduced CXCR4 protein expression through downregulating Protein Kinase-B (Akt)/Mammalian Target of Rapamycin (mTOR) signaling pathway. In cells transfected with constitutively active Akt plasmids, a reverse effect of Salmonella-induced inhibition of CXCR4 was observed. Tumor cells have chemotactic response to CXCL12 in migration assay, and we found that Salmonella reduced tumor chemotactic response after CXCL12 treatment. The C57BL/6 mice were intravenously injected with B16F10 and LL2 cells pre-incubated with or without Salmonella, the tumor size and lung weight of Salmonella group had obviously decreased, indicating anti-metastatic effect that confirmed the findings from the in vitro experiments.
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Quimiocina CXCL12/metabolismo , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias/terapia , Receptores CXCR4/metabolismo , Vacinas contra Salmonella/imunologia , Animais , Linhagem Celular Tumoral , Quimiotaxia/imunologia , Regulação para Baixo/imunologia , Humanos , Camundongos , Neoplasias/imunologia , Neoplasias/patologia , Salmonella/imunologia , Vacinas contra Salmonella/administração & dosagemRESUMO
Salmonella causes salmonellosis, is a facultative anaerobe and is one of the common Gram-negative bacteria. Salmonella has anti-tumor potential and tumor-targeting activity. The heparin sulfate on cell surfaces can be cleaved by heparanase that is an endo-ß-D-glucuronidase. Heparanase can destroy the extracellular matrix and is involved in tumor metastasis and angiogenic activity. Previously, Salmonella was demonstrated to inhibit tumor metastasis. It remains unclear whether Salmonella inhibits metastasis by regulating heparanase. The expression of heparanase in Salmonella-treated tumor cells was found to be decreased. Transwell and wound-healing assays demonstrated the inhibition of cell migration after Salmonella treatment. Salmonella was found to influence the levels of phosphate-protein kinase B (P-AKT) and phosphate-extracellular regulated protein kinases (P-ERK), which are involved in heparanase expression. Salmonella reduced the heparanase expression induced upregulating PERK and PAKT signaling pathways. The mice bearing an experimental metastasis tumor model was used to evaluate the anti-tumor metastatic effects of Salmonella. Compared with the control group, Salmonella significantly reduced the number of metastatic nodules and enhanced survival. The results of our study indicate that Salmonella plays a vital role in the inhibition of tumor metastasis through the downregulation of heparanase.
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Regulação Neoplásica da Expressão Gênica/imunologia , Glucuronidase/metabolismo , Neoplasias/terapia , Vacinas contra Salmonella/imunologia , Animais , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Regulação para Baixo/imunologia , Humanos , Camundongos , Neoplasias/imunologia , Neoplasias/patologia , Salmonella/imunologia , Vacinas contra Salmonella/administração & dosagemRESUMO
Targeting metastasis is a vital strategy to improve the clinical outcome of cancer patients, specifically in cases with high-grade malignancies. Here, we employed a Salmonella-based treatment to address metastasis. The potential of Salmonella as an anticancer agent has been extensively studied; however, the mechanism through which it affects metastasis remains unclear. This study found that the epithelial-to-mesenchymal transition (EMT) inducer SNAI1 was markedly reduced in Salmonella-treated melanoma cells, as revealed by immunoblotting. Furthermore, wound healing and transwell assays showed a reduced in vitro cell migration following Salmonella treatment. Transfection experiments confirmed that Salmonella acted against metastasis by suppressing protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling, which in turn inhibited SNAI1 expression. Since it is known that metastasis is also influenced by inflammation, we partly characterized the immune infiltrates in melanoma as affected by Salmonella treatment. We found through tumor-macrophage co-culture that Salmonella treatment increased high mobility group box 1 (HMGB1) secretion in tumors to coax the polarization of macrophages in favor of an M1-like phenotype, as shown by increased inducible nitric oxide synthase (iNOS) expression and Interleukin 1 Beta (IL-1ß) secretion. Data from our animal study corroborated the in vitro findings, wherein the Salmonella-treated group obtained the lowest lung metastases, longer survival, and increased iNOS-expressing immune infiltrates.
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BACKGROUND: Currently, as the coronavirus disease (COVID-19) has become a pandemic, rapidly obtaining accurate information of patient symptoms and their progression is crucial and vital. Although the early studies in China have illustrated that the representative symptoms of COVID-19 include (dry) cough, fever, headache, fatigue, gastrointestinal discomfort, dyspnea, and muscle pain, there is increasing evidence to suggest that olfactory and taste disorder are related to the COVID-19 pandemic. Therefore, we conduct this study to review the present literature about the correlation between anosmia or dysgeusia and COVID-19. METHODS: A comprehensive literature search in 2020 of the electronic journal databases, mainly PubMed or Web of Science, was performed using the keywords COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with hyposmia, anosmia, dysgeusia, olfactory disorder, or olfactory dysfunction. The country, study period, case number, inpatient or outpatient medical visit, evaluation method (subjective complaints of dysfunction or objective evaluation), and occurrence rate of olfactory or gustatory function were reviewed. RESULTS: Many studies reported that the recoverable olfactory or gustatory dysfunction may play an important role as the early clinical symptom of COVID-19. It is associated with better prognosis, although further investigation and validation should be carried out. CONCLUSION: Studies have shown that smell and taste disturbances may represent an early symptom of COVID-19 and healthcare professionals must be very vigilant when managing patients with these symptoms. In the pandemic era, this implies testing for COVID-19 by healthcare workers with full personal protective equipment.
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COVID-19/complicações , Transtornos do Olfato/etiologia , SARS-CoV-2 , Distúrbios do Paladar/etiologia , Enzima de Conversão de Angiotensina 2/fisiologia , COVID-19/diagnóstico , Teste para COVID-19 , HumanosRESUMO
Glycine N-methyltransferase (GNMT) regulates S-adenosylmethionine (SAMe), a methyl donor in methylation. Over-expressed SAMe may cause neurogenic capacity reduction and memory impairment. GNMT knockout mice (GNMT-KO) was applied as an experimental model to evaluate its effect on neurons. In this study, proteins from brain tissues were studied using proteomic approaches, Haemotoxylin and Eosin staining, immunohistochemistry, Western blotting, and ingenuity pathway analysis. The expression of Receptor-interacting protein 1(RIPK1) and Caspase 3 were up-regulated and activity-dependent neuroprotective protein (ADNP) was down-regulated in GNMT-KO mice regardless of the age. Besides, proteins related to neuropathology, such as excitatory amino acid transporter 2, calcium/calmodulin-dependent protein kinase type II subunit alpha, and Cu-Zn superoxide dismutase were found only in the group of aged wild-type mice; 4-aminobutyrate amino transferase, limbic system-associated membrane protein, sodium- and chloride-dependent GABA transporter 3 and ProSAAS were found only in the group of young GNMT-KO mice and are related to function of neurons; serum albumin and Rho GDP dissociation inhibitor 1 were found only in the group of aged GNMT-KO mice and are connected to neurodegenerative disorders. With proteomic analyses, a pathway involving Gonadotropin-releasing hormone (GnRH) signal was found to be associated with aging. The GnRH pathway could provide additional information on the mechanism of aging and non-aging related neurodegeneration, and these protein markers may be served in developing future therapeutic treatments to ameliorate aging and prevent diseases.
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Envelhecimento/metabolismo , Biomarcadores , Doenças Neurodegenerativas/metabolismo , Animais , Biomarcadores/metabolismo , Encéfalo , Senescência Celular , Modelos Animais de Doenças , Suscetibilidade a Doenças , Imuno-Histoquímica , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/etiologia , Neurônios/metabolismo , Prognóstico , Proteoma , Proteômica/métodos , Transdução de Sinais/efeitos dos fármacosRESUMO
Chloroquine (CQ) and its derivative, hydroxychloroquine (HCQ), have attracted wide attention for treating coronavirus disease 2019 (COVID-19). However, conflicting outcomes have been found in COVID-19 clinical trials after treatment with CQ or HCQ. To date, it remains uncertain whether CQ and HCQ are beneficial antiviral drugs for combating COVID-19. We performed a systematic review to depict the efficacy of CQ or HCQ for the treatment of COVID-19. The guidelines of PRISMA were used to conduct this systematic review. We searched through articles from PubMed, Web of Science and other sources that were published from 1 January 2020 to 31 October 2020. The search terms included combinations of human COVID-19, CQ, and HCQ. Eleven qualitative articles comprising of four clinical trials and seven observation studies were utilized in our systematic review. The analysis shows that CQ and HCQ do not have efficacy in treatment of patients with severe COVID-19. In addition, CQ and HCQ have caused life-threatening adverse reactions which included cardiac arrest, electrocardiogram modification, and QTc prolongation, particularly during the treatment of patients with severe COVID-19. Our systematic review suggested that CQ and HCQ are not beneficial antiviral drugs for curing patients with severe COVID-19. The treatment effect of CQ and HCQ is not only null but also causes serious side effects, which may cause potential cardiotoxicity in severe COVID-19 patients.
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Bacteria response to their environment by producing some compounds which are used in cosmetic and pharmaceutical applications. Some probiotics can regulate immune response and modulate the symptoms of several diseases. Bacteria affect skin response to skin care products. Bacteria are thought to play an important role in acne incidence, skin moisture, and nutrient metabolism, but only a few studies have focused on the extracts of Lactobacillus plantarum in skin care. In this study, we identified that L. plantarum-GMNL6 enhanced collagen synthesis and the gene expression of serine palmitoyltransferase small subunit A. Meanwhile, L. plantarum-GMNL6 reduced the melanin synthesis, the biofilm of Staphylococcus aureus, and the proliferation of Cutibacterium acnes. Information from clinical observation during the ointment for external face use in people displayed that the syndromes of skin moisture, skin color, spots, wrinkles, UV spots, and porphyrins were improved. The diversification of human skin microbiomes was affected by smearing the face of volunteers with L. plantarum-GMNL6. Understanding the potential mechanisms of the action of L. plantarum-GMNL6 in dermatologic conditions promotes the development of care products.
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Lactobacillus plantarum/imunologia , Microbiota/imunologia , Probióticos/administração & dosagem , Higiene da Pele/métodos , Pele/microbiologia , Adulto , Animais , Biofilmes/crescimento & desenvolvimento , Linhagem Celular Tumoral , Colágeno/biossíntese , Feminino , Fibroblastos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Pomadas , Propionibacteriaceae/crescimento & desenvolvimento , Propionibacteriaceae/imunologia , Propionibacteriaceae/isolamento & purificação , Pele/imunologia , Pele/metabolismo , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/imunologia , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento , Adulto JovemRESUMO
Esophageal squamous cell carcinoma (ESCC) is a major cancer prevalent in Asian males. Pretreatment tumor burden can be prognostic for ESCC. We studied the prognostic value of metabolic parameters of 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) and the serum squamous cell carcinoma antigen (SCC-Ag) level in node-negative stage II ESCC patients. Eighteen males underwent staging evaluation were included. The volume-based metabolic parameters derived from 18F-FDG PET/CT, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were obtained using the PET Volume Computer Assisted Reading application. The Spearman correlation coefficients were calculated to assess the relationship between metabolic parameters and pretreatment serum SCC-Ag levels. Based on the 5-year follow-up, patients were sub-divided into the demised and the stable groups. Potential prognostic value was assessed by independent t-test and the Mann-Whitney U test. The association of overall survival was assessed using univariate and multivariate Cox regression analyses. The demised group showed significant higher values in serum SCC-Ag, as well as in MTV and TLG, but not SUVmax and SUVmean. The SUVmax, MTV, TLG, and serum SCC-Ag showed significant association with overall survival. Our findings suggest potential usage of pretreatment volume-based metabolic parameters of 18F-FDG PET/CT and serum SCC-Ag as prognostic factors for node-negative stage II ESCC patients.
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A polysaccharide isolated from the radix of Astragalus membranaceus, called PG2, used in traditional Chinese medicine, with potential hematopoiesis inducing and immunomodulation activities. PG2 extracted from A. membranaceus has been demonstrated as a novel alternative medicine for cancer patients. Recently, we demonstrated that PG2 enhanced chemotherapy through bystander effect and reduced the expression of indoleamine 2, 3-dioxygenase 1 in tumor cells. Many tumors have been proven to have a high expression of programmed cell death protein ligand-1 (PD-L1), which binds with programmed cell death protein-1(PD-1) in immune cells, thus causing immune tolerance within the tumor microenvironment. With decreased expression of PD-L1, increased immune response can be observed, which might be helpful when developing tumor immunotherapy. The antitumor therapeutic effect mediated by PG2 may associate with an inflammatory immune response at the tumor site. However, the molecular mechanism that by which PG2 inhibits PD-L1 is still incompletely known. The expression of PD-L1 was decreased after tumor cells were treated with PG2. In addition, the cell signaling pathway in tumor cells was evaluated by Western blotting analysis after PG2 treatment. PG2 can downregulate the expression of PD-L1 on the cell surface via the protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase beta-1 (p70S6K) pathway. In conclusion, our results indicate that PG2 inhibits PD-L1 expression and plays a crucial role in immunotherapy, which might be a promising strategy combined with other treatments.