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1.
J Environ Sci (China) ; 141: 40-50, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38408833

RESUMO

The Tibetan Plateau, known as the "Third Pole", is currently in a state of perturbation caused by intensified human activity. In this study, 56 samples were obtained at the five sampling sites in typical area of Lhasa city and their physical and chemical properties were investigated by TEM/EDS, STXM, and NEXAFS spectroscopy. After careful examination of 3387 single particles, the results showed that Fe should be one of the most frequent metal elements. The Fe-containing single particles in irregular shape and micrometer size was about 7.8% and might be mainly from local sources. Meanwhile, the Fe was located on the subsurface of single particles and might be existed in the form of iron oxide. Interestingly, the core-shell structure of iron-containing particles were about 38.8% and might be present as single-, dual- or triple-core shell structure and multi-core shell structure with the Fe/Si ratios of 17.5, 10.5, 2.9 and 1.2, respectively. Meanwhile, iron and manganese were found to coexist with identical distributions in the single particles, which might induce a synergistic effect between iron and manganese in catalytic oxidation. Finally, the solid spherical structure of Fe-containing particles without an external layer were about 53.4%. The elements of Fe and Mn were co-existed, and might be presented as iron oxide-manganese oxide-silica composite. Moreover, the ferrous and ferric forms of iron might be co-existed. Such information can be valuable in expanding our understanding of Fe-containing particles in the Tibetan Plateau atmosphere.


Assuntos
Compostos Férricos , Ferro , Manganês , Humanos , Ferro/química , Tibet , Microscopia Eletrônica de Transmissão
2.
World J Clin Cases ; 12(5): 988-994, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38414599

RESUMO

BACKGROUND: The most common causes of scrotal enlargement in patients include primary tumor of the scrotum, inflammation, hydrocele of the tunica vaginalis, and indirect inguinal hernia; scrotal enlargement caused by external tumors of the scrotum is rare. The patient had both a greater omentum tumor and an inguinal hernia, and the tumor protruded into the scrotum through the hernia sac, which is even rarer. Moreover, omental tumors are mostly metastatic, and primary omental fibroma is rare. CASE SUMMARY: Here, we report a rare case of a 25-year-old young man with scrotal enlargement and pain for 3 months. Preoperative examination and multidisciplinary discussions considered intra-abdominal tumor displacement and inguinal hernia, and intraoperative exploration confirmed that the greater omentum tumor protruded into the scrotum. Therefore, tumor resection and tension-free inguinal hernia repair were performed. The final diagnosis was benign fibroma of the greater omentum accompanied by an indirect inguinal hernia. CONCLUSION: This unusual presentation of a common inguinal hernia disease illustrates the necessity of performing detailed history taking, physical examination, and imaging before surgery.

3.
Chin J Dent Res ; 26(2): 69-75, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37395518

RESUMO

OBJECTIVE: To investigate the potential effect of small molecule nitazoxanide (NTZ) on the osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS: Cell counting Kit-8 assay was used to examine the effect of NTZ on proliferation of BMSCs. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis were used to measure the expression of osteogenic and adipogenic marker gene. Alkaline phosphatase (ALP) staining and activity assay and Alizarin Red S (ARS) staining were used to investigate the effect of NTZ on osteogenesis. Oil red O (ORO) staining assay was used to assess the impact of NTZ on adipogenesis. RESULTS: NTZ significantly suppressed the osteogenic differentiation but promoted the adipogenic differentiation of BMSCs. Mechanistically, NTZ regulated osteogenic/adipogenic differentiation of BMSCs by inhibiting the Wnt/ß-catenin signalling pathway. The addition of Wnt/ß-catenin signalling pathway activator, lithium chloride, could reverse the effect of NTZ on BMSCs. CONCLUSION: NTZ affected osteogenic and adipogenic differentiation of BMSCs with the involvement of Wnt/ß-catenin signalling pathway. This finding expanded the understanding of NTZ pharmacology and indicated that NTZ might have an adverse effect on bone homeostasis.


Assuntos
Adipogenia , Células-Tronco Mesenquimais , Osteogênese/genética , beta Catenina/genética , beta Catenina/metabolismo , beta Catenina/farmacologia , Diferenciação Celular , Corantes , Células Cultivadas
4.
Zhongguo Zhong Yao Za Zhi ; 48(8): 2000-2009, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37282890

RESUMO

Lung cancer is one of the common malignant tumors in the world, and its incidence and mortality is increasing year by year. Interactions between tumor cells and immune cells in the tumor microenvironment(TME) affect tumor proliferation, infiltration, and metastasis. Tumor-associated macrophages(TAMs) are prominent components of TME, and they have dual regulation effects on malignant progression of lung cancer. The number, activity, and function of M2 macrophages are related to the poor prognosis of lung cancer, and M2 macrophages participate in tumor angiogenesis and immune escape. It has been proved that traditional Chinese medicines(TCMs) and their active ingredients can enhance the antitumor effects, reduce the toxicity of chemotherapy and radiotherapy, and prolong the survival rates of patients with cancer. This paper summarized the role of TAMs in the lung cancer initiation and progression, explored the molecular mechanism of TCM in regulating the recruitment, polarization phenotype, activity, and expression of related factors and proteins of TAMs, and discussed related signal pathways in the prevention and treatment of lung cancer based on the TCM theory of "reinforcing healthy qi and eliminating pathogen". This paper is expected to provide new ideas for the immunotherapy of targeted TAMs.


Assuntos
Neoplasias Pulmonares , Macrófagos Associados a Tumor , Humanos , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia , Medicina Tradicional Chinesa , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Macrófagos , Imunoterapia , Microambiente Tumoral
5.
Hemoglobin ; 47(2): 49-51, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37247201

RESUMO

Deletional α-thalassemia is characterized by reduced hemoglobin A2 and involves the deletion of a few nucleotides, which is a rare hereditary disease. However, the detection of rare mutations using commonly used genetic tests is highly challenging. In the present study, next-generation sequencing (NGS) was used to identify a novel 7-bp deletion α-thalassemia in one individual from a Chinese family. Hematological parameters of the family members were determined using an automated cell counter, and hemoglobin electrophoresis was performed using a capillary electrophoresis system. Subsequently, NGS was performed on the genomic DNA of the patient and her family members. The 7-bp deletion (named Hb Honghe [HBA1: c.401_407delGCACCGT]) of α-thalassemia in the α-globin gene was confirmed using Sanger sequencing. The patient's father was also a heterozygous carrier of HBA1: c.401_407delGCACCGT deletion, but not her mother or sister. The application of the combined molecular approach is essential for the accurate diagnosis of rare thalassemia. This study reports a novel case of α- thalassemia. The characterization of the mutation might provide new insights into genetic counseling and accurate diagnosis of thalassemia.


Assuntos
Talassemia alfa , Humanos , Talassemia alfa/diagnóstico , Talassemia alfa/genética , alfa-Globinas/genética , Hemoglobinas Glicadas , População do Leste Asiático , Mutação , Família Multigênica , Deleção de Genes
6.
Am J Physiol Heart Circ Physiol ; 324(4): H528-H541, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36867446

RESUMO

Takotsubo syndrome (TTS) is characterized by short-term contractile dysfunction with its mechanism undefined. We showed that activation of cardiac Hippo pathway mediates mitochondrial dysfunction and that stimulation of ß-adrenoceptors (ßAR) activates Hippo pathway. Here, we investigated the role of ßAR-Hippo signaling in mediating mitochondrial dysfunction in isoproterenol (Iso)-induced TTS-like mouse model. Elderly postmenopausal female mice were administered with Iso (1.25 mg/kg/h for 23 h). Cardiac function was determined by serially echocardiography. At days 1 and 7 post-Iso exposure, mitochondrial ultrastructure and function were examined by electron microscopy and various assays. Alterations in cardiac Hippo pathway and effects of genetic inactivation of Hippo kinase (Mst1) on mitochondrial damage and dysfunction in the acute phase of TTS were investigated. Isoproterenol exposure induced acute increase in biomarkers of cardiac damage and ventricular contractile dysfunction and dilation. At day 1 post-Iso, we observed extensive abnormalities in mitochondrial ultrastructure, downregulation of mitochondrial marker proteins, and mitochondrial dysfunction evidenced by lower ATP content, increased lipid droplets, higher contents of lactate, and augmented reactive oxygen species (ROS). All changes were reversed by day 7. ßAR stimulation led to activation of cardiac Hippo pathway with enhanced expression of Hippo kinase Mst1 and inhibitory YAP phosphorylation, as well as reduced nuclear YAP-TEAD1 interaction. In mice with cardiac expression of inactive mutant Mst1 gene, acute mitochondrial damage and dysfunction were mitigated. Stimulation of cardiac ßAR activates Hippo pathway that mediates mitochondrial dysfunction with energy insufficiency and enhanced ROS, promoting acute but short-term ventricular dysfunction.NEW & NOTEWORTHY Takotsubo syndrome (TTS) is featured by activation of sympatho-ß-adrenoceptor (ßAR) system leading to acute loss of ventricular contractile performance. However, the molecular mechanism remains undefined. We demonstrated, in an isoproterenol-induced murine TTS-like model, extensive mitochondrial damage, metabolic dysfunction, and downregulated mitochondrial marker proteins, changes temporarily associated with cardiac dysfunction. Mechanistically, stimulation of ßAR activated Hippo signaling pathway and genetic inactivation of Mst1 kinase ameliorated mitochondrial damage and metabolic dysfunction at the acute phase of TTS.


Assuntos
Via de Sinalização Hippo , Cardiomiopatia de Takotsubo , Feminino , Camundongos , Animais , Cardiomiopatia de Takotsubo/induzido quimicamente , Isoproterenol , Espécies Reativas de Oxigênio , Modelos Animais de Doenças , Receptores Adrenérgicos beta
7.
Theranostics ; 13(2): 560-577, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36632235

RESUMO

Rationale: Chemotherapy is a common clinical strategy for cancer treatment. However, the accompanied cardiomyopathy renders cancer patients under risk of another life-threatening condition. Whereas Hippo pathway is known to play key roles in both cancerogenesis and heart disease, it remains unclear whether Hippo pathway activation mediates chemotherapy-induced cardiomyopathy. Methods and Results: In human breast cancer cells, doxorubicin (DOX) significantly induced upregulation of Hippo kinase Mst1, inhibitory phosphorylation of YAP, mitochondrial damage, reduced cell viability and increased apoptosis. Hippo pathway inactivation by Mst1-siRNA transfection effectively improved cell survival and mitigated mitochondrial damage and cell apoptosis. Another anti-cancer drug YAP inhibitor verteporfin also induced lower cancer cell viability, apoptosis and mitochondrial injury. Chronic treatment with DOX in vivo (4 mg/kg/week for 6 weeks) caused mitochondrial damage and dysfunction, oxidative stress and cardiac fibrosis, while acute DOX treatment (16 mg/kg single bolus) also induced myocardial oxidative stress and mitochondrial abnormalities. Chronic treatment with verteporfin (2 months) resulted in cardiomyopathy phenotypes comparable to that by chronic DOX regimen. In transgenic mice with cardiac overexpression of kinase-dead mutant Mst1 gene, these adverse cardiac effects of DOX were significantly attenuated relative to wild-type littermates. Conclusions: Anti-cancer action of both DOX and verteporfin is associated with Hippo pathway activation. Such action on cardiac Hippo pathway mediates mitochondrial damage and cardiomyopathy.


Assuntos
Antineoplásicos , Cardiomiopatias , Via de Sinalização Hippo , Neoplasias , Animais , Humanos , Camundongos , Apoptose , Cardiomiopatias/induzido quimicamente , Cardiotoxicidade/etiologia , Doxorrubicina/farmacologia , Via de Sinalização Hippo/efeitos dos fármacos , Camundongos Transgênicos , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Neoplasias/tratamento farmacológico , Estresse Oxidativo , Verteporfina/farmacologia , Verteporfina/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico
8.
J Cardiovasc Pharmacol ; 81(4): 259-269, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36668724

RESUMO

ABSTRACT: Mitochondrial dysfunction plays a key role in the development of heart failure, but targeted therapeutic interventions remain elusive. Previous studies have shown coenzyme Q10 (CoQ10) insufficiency in patients with heart disease with undefined mechanism and modest effectiveness of CoQ10 supplement therapy. Using 2 transgenic mouse models of cardiomyopathy owing to cardiac overexpression of Mst1 (Mst1-TG) or ß 2 -adrenoceptor (ß 2 AR-TG), we studied changes in cardiac CoQ10 content and alterations in CoQ10 biosynthesis genes. We also studied in Mst1-TG mice effects of CoQ10, delivered by oral or injection regimens, on both cardiac CoQ10 content and cardiomyopathy phenotypes. High performance liquid chromatography and RNA sequencing revealed in both models significant reduction in cardiac content of CoQ10 and downregulation of most genes encoding CoQ10 biosynthesis enzymes. Mst1-TG mice with 70% reduction in cardiac CoQ10 were treated with CoQ10 either by oral gavage or i.p. injection for 4-8 weeks. Oral regimens failed in increasing cardiac CoQ10 content, whereas injection regimen effectively restored the cardiac CoQ10 level in a time-dependent manner. However, CoQ10 restoration in Mst1-TG mice did not correct mitochondrial dysfunction measured by energy metabolism, downregulated expression of marker proteins, and oxidative stress nor to preserve cardiac contractile function. In conclusion, mouse models of cardiomyopathy exhibited myocardial CoQ10 deficiency likely due to suppressed endogenous synthesis of CoQ10. In contrast to ineffectiveness of oral administration, CoQ10 administration by injection regimen in cardiomyopathy mice restored cardiac CoQ10 content, which, however, failed in achieving detectable efficacy at molecular and global functional levels.


Assuntos
Cardiomiopatias , Ubiquinona , Camundongos , Animais , Ubiquinona/metabolismo , Ubiquinona/uso terapêutico , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/genética , Coração , Camundongos Transgênicos
9.
Dalton Trans ; 52(5): 1177-1181, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36648495

RESUMO

Simple synthetic modulation based on thorium nitrate and tris((4-carboxyl)phenylduryl)amine (H3TCBPA) gives rise to a new thorium-based metal-organic framework, Th-TCBPA, which features excellent hydrolytic and thermal stabilities. Incorporating electron-rich TCBPA3- linkers not only endows Th-TCBPA with high adsorption capacity toward radioiodine vapor, but also makes it a luminescence sensor for the highly sensitive and selective detection of Cr(VI) anions.

10.
Int J Pharm ; 631: 122509, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36549403

RESUMO

Immune checkpoint inhibitors (ICIs) represent a new class of immunotherapy drugs, and are used to relieve immune suppression or enhance the immune response through the blockade of checkpoint ligands or receptors. ICIs have achieved great success in clinical cancer treatment. Monoamine oxidase A (MAOA) is a potent immune checkpoint of immunotherapy. Recently, it has been reported that MAOA inhibitors could enhance CD8+ T cell activity by upregulating 5-HT autocrine pathway in T cells. In this study, we synthesized doxorubicin (DOX) and isoniazid (INH, a MAOA inhibitor) conjugates through a pH sensitive hydrazone bond. Results of the in vivo studies showed that DOX-INH could effectively enhance the activity of CD8+ T cells and perform a synergistic anti-tumor effect with PD-L1 small molecular inhibitor (BMS202). In addition, in an orthotopic 4T1 breast cancer model, it was demonstrated that DOX-INH could inhibit the epithelial-mesenchymal transition process by blocking Shh, IL-6, and TGF-ß signaling pathways, thereby inhibiting the growth and metastasis of breast cancer. Thus, a simple and effective small molecule conjugate produced by the combination of a chemotherapy drug and a MAOA inhibitor shows broad prospect in cancer therapy.


Assuntos
Neoplasias da Mama , Isoniazida , Humanos , Feminino , Isoniazida/química , Microambiente Tumoral , Linfócitos T CD8-Positivos , Doxorrubicina , Neoplasias da Mama/tratamento farmacológico , Imunoterapia , Imunidade , Linhagem Celular Tumoral
11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981333

RESUMO

Lung cancer is one of the common malignant tumors in the world, and its incidence and mortality is increasing year by year. Interactions between tumor cells and immune cells in the tumor microenvironment(TME) affect tumor proliferation, infiltration, and metastasis. Tumor-associated macrophages(TAMs) are prominent components of TME, and they have dual regulation effects on malignant progression of lung cancer. The number, activity, and function of M2 macrophages are related to the poor prognosis of lung cancer, and M2 macrophages participate in tumor angiogenesis and immune escape. It has been proved that traditional Chinese medicines(TCMs) and their active ingredients can enhance the antitumor effects, reduce the toxicity of chemotherapy and radiotherapy, and prolong the survival rates of patients with cancer. This paper summarized the role of TAMs in the lung cancer initiation and progression, explored the molecular mechanism of TCM in regulating the recruitment, polarization phenotype, activity, and expression of related factors and proteins of TAMs, and discussed related signal pathways in the prevention and treatment of lung cancer based on the TCM theory of "reinforcing healthy qi and eliminating pathogen". This paper is expected to provide new ideas for the immunotherapy of targeted TAMs.


Assuntos
Humanos , Macrófagos Associados a Tumor/patologia , Medicina Tradicional Chinesa , Neoplasias Pulmonares/genética , Macrófagos , Imunoterapia , Microambiente Tumoral
12.
Insects ; 13(6)2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35735871

RESUMO

The guava fruit fly, Bactrocera correcta, is one of the most destructive pests in the genus Bactrocera and detects environmental odorants mainly through antennal olfactory sensilla phenotypes with nanopores. However, it is unclear whether there are naturally occurring abnormal antennal olfactory sensilla phenotypes that affect olfaction. Here, we found that there were abnormal bulges besides nanopores on the surface of trichoid and basiconic olfactory sensilla in the antennal flagellum of long-term laboratory rearing colony (LTC), and that nanopore number in these olfactory sensilla was also remarkably reduced. Notably, the electroantennogram (EAG) responses of LTC insects to methyl eugenol or ß-caryophyllene were inhibited, and their behavioral responses elicited by the same odorants were also impaired. These results revealed naturally occurring abnormal antennal olfactory sensilla phenotypes which were involved in olfactory deficit in B. correcta, providing a platform to further study nanopore-targeted pest control technologies in the future.

13.
AIDS Behav ; 26(9): 2941-2953, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35277807

RESUMO

Black/African American (Black) versus White persons are unequally burdened by human immunodeficiency virus (HIV) in the United States. Structural factors can influence social determinants of health, key components in reducing HIV-related health inequality by race. This analysis examined HIV care outcomes among Black and White persons with diagnosed HIV (PWDH) in relation to three structural factors: racial redlining, Medicaid expansion, and Ryan White HIV/AIDS Program (RWHAP) use. Using National HIV Surveillance System, U.S. Census, and Home Mortgage Disclosure Act data, we examined linkage to HIV care and viral suppression (i.e., viral load < 200 copies/mL) in relation to the structural factors among 12,996 Black and White PWDH with HIV diagnosed in 2017/alive at year-end 2018, aged ≥ 18 years, and residing in 38 U.S. jurisdictions with complete laboratory data, geocoding, and census tract-level redlining indexes. Compared to White PWDH, a lower proportion of Black PWDH were linked to HIV care within 1 month after diagnosis and were virally suppressed in 2018. Redlining was not associated with the HIV care outcomes. A higher prevalence of PWDH residing (v. not residing) in states with Medicaid expansion were linked to HIV care ≤ 1 month after diagnosis. A higher prevalence of those residing (v. not residing) in states with > 50% of PWDH in RWHAP had viral suppression. Direct exposure to redlining was not associated with poor HIV care outcomes. Structural factors that reduce the financial burden of HIV care and improve care access like Medicaid expansion and RWHAP might improve HIV care outcomes of PWDH.


Assuntos
Infecções por HIV , População Negra , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Disparidades nos Níveis de Saúde , Humanos , Medicaid , Estados Unidos/epidemiologia , Carga Viral
14.
Public Health Rep ; 137(2): 278-290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33629905

RESUMO

OBJECTIVE: Social and structural factors, referred to as social determinants of health (SDH), create pathways or barriers to equitable sexual health, and information on these factors can provide critical insight into rates of diseases such as HIV. Our objectives were to describe and identify differences, by race/ethnicity and geography, in SDH among adults with HIV. METHODS: We conducted an ecological study to explore SDH among people with HIV diagnosed in 2017, by race/ethnicity and geography, at the census-tract level in the United States and Puerto Rico. We defined the least favorable SDH as the following: low income (<$40 000 in median annual household income), low levels of education (≥18% of residents have

Assuntos
Etnicidade , Infecções por HIV , Adulto , Setor Censitário , Feminino , Geografia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Masculino , Porto Rico/epidemiologia , Determinantes Sociais da Saúde , Estados Unidos/epidemiologia
15.
Public Health Rep ; 137(3): 525-536, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33882743

RESUMO

OBJECTIVE: People who inject drugs are among the groups most vulnerable to HIV infection. The objective of this study was to describe differences in the geographic distribution of HIV diagnoses and social determinants of health (SDH) among people who inject drugs (PWID) who received an HIV diagnosis in 2017. METHODS: We used data from the National HIV Surveillance System (NHSS) to determine the counts and percentages of PWID aged ≥18 with HIV diagnosed in 2017. We combined these data with data from the US Census Bureau's American Community Survey at the census tract level to examine regional, racial/ethnic, and population-area-of-residence differences in poverty status, education level, income level, employment status, and health insurance coverage. RESULTS: We observed patterns of disparity in HIV diagnosis counts and SDH among the 2666 PWID with a residential address linked to a census tract, such that counts of HIV diagnosis increased as SDH outcomes became worse. The greatest proportion of PWID lived in census tracts where ≥19% of the residents lived below the federal poverty level, ≥18% of the residents had

Assuntos
Infecções por HIV , Abuso de Substâncias por Via Intravenosa , Etnicidade , Infecções por HIV/diagnóstico , Humanos , Grupos Raciais , Determinantes Sociais da Saúde , Abuso de Substâncias por Via Intravenosa/epidemiologia , Estados Unidos/epidemiologia
16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-940589

RESUMO

ObjectiveTo investigate the effects and mechanism of baicalin (BA) on lipopolysaccharide (LPS)-induced acute lung injury in rats. MethodEighty healthy male SD rats were randomly divided into the control group, model group, low-dose BA (BA-L) group, medium-dose BA (BA-M) group, high-dose BA (BA-H) group, dexamethasone (DEX) group, SB203580 group, and BA + SB203580 group, with 10 rats in each group. The rats in the BA-L, BA-M, and BA-H groups were injected intraperitoneally with different doses (10, 50, 100 mg·kg-1) of BA solution, the ones in the DEX group with 5 mg·kg-1 DEX solution, the ones in the SB203580 group with 0.5 mg·kg-1 SB203580 solution, the ones in the BA + SB203580 group with 100 mg·kg-1 BA solution and 0.5 mg·kg-1 SB203580, and those in both the control group and model group with the same volume of normal saline, once per day, for seven successive days. One hour after the last administration, rats in all groups except for the control group were given 5 mg·kg-1 LPS via intratracheal instillation for inducing the acute lung injury, whereas those in the control group received the same volume of normal saline solution. Twelve hours later, the lung tissues were sampled and stained with htoxylin-eosin (HE) for observing the pathological changes, followed by the counting of the total number of cells and neutrophils in bronchoalveolar lavage fluid (BALF). The wet/dry weight ratio of the lung tissue and the contents of serum superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. The activity of reactive oxygen species (ROS) in the lung tissue was detected by immunofluorescence and the levels of interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in BALF by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) was conducted to determine the relative expression of p-p38 mitogen-activated protein kinase (MAPK) and Western blotting was carried out to detect the protein expression levels of p-p38 MAPK, thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), and cysteinyl aspartate specific protease-1 (Caspase-1) in the lung tissue. ResultCompared with the control group, the model group displayed inflammatory pathological changes in lung tissue, elevated wet/dry weight ratio, total number of cells and neutrophils in BALF, and ROS and MDA levels (P<0.01), decreased SOD activity (P<0.01), and up-regulated IL-1, IL-18, IL-6, TNF-α, p-p38 MAPK, NLRP3, and Caspase-1 expression (P<0.01). Compared with the model group, BA at different doses, SB203580, and BA + SB203580 all effectively alleviated the pathological changes in lung tissue induced by LPS, reduce the lung wet/dry weight ratio, the total number of cells and neutrophils in BALF, and ROS and MDA levels (P<0.05,P<0.01), enhanced the activity of SOD (P<0.05,P<0.01), and down-regulated the expression of IL-1β, IL-18, IL-6,TNF-α, p-p38 MAPK, NLRP3, and Caspase-1 in lung tissue (P<0.05,P<0.01). ConclusionBA has a protective effect against LPS-induced acute lung injury, which may be related to its inhibition of p38MAPK/NLRP3 signaling pathway and the improvement of inflammatory response.

17.
Int J Pharm ; 607: 121027, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34418473

RESUMO

Cancer immunotherapy often fails to result in a favorable outcome owing to poor activation of immune response, the immunosuppressive tumor microenvironment, and systemic toxicity. In this study, indocyanine green (ICG) was conjugated with doxorubicin (DOX) using a hydrazone linker (DOX-ICG). Results of our in vitro and in vivo studies indicated that DOX-ICG could trigger powerful immunogenic cell death (ICD) of tumor cells. Moreover, its use in combination with immune checkpoint inhibitors could effectively inhibit both primary and abscopal tumors growth and suppress tumor metastasis. Therefore, this simple, safe, and efficient prodrug shows great potential for use in photo-activated chemo-immunotherapy.


Assuntos
Morte Celular Imunogênica , Neoplasias , Linhagem Celular Tumoral , Doxorrubicina , Humanos , Imunoterapia , Verde de Indocianina , Neoplasias/tratamento farmacológico , Microambiente Tumoral
18.
Appl Opt ; 60(8): 2441-2449, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33690344

RESUMO

In this paper, a Si3N4-CaF2 hybrid plasmonic waveguide (HPW) with an asymmetric metal cladding is designed for the mid-infrared polarization rotator (PR). The mode characteristics and polarization rotation performances of the Si3N4-CaF2 HPW-based PR are simulated by using the finite element method. Operating at the wavelength of 3.5 µm, the polarization conversion efficiency between two polarization modes (PM 1 and PM 2) is larger than 99% at a Si3N4-CaF2 HPW length of 104 µm. The Si3N4-CaF2 HPW-based PR maintains good polarization rotation performances within fabrication tolerances from -10 to 10 nm. The polarization rotator based on the Si3N4-CaF2 HPW paves the way to achieve integrated waveplates, driving many important optical functions from free space onto a chip.

19.
Public Health Rep ; 136(6): 685-698, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33563091

RESUMO

OBJECTIVE: HIV disproportionately affects Hispanic/Latino people in the United States, and factors other than individual attributes may be contributing to these differences. We examined differences in the distribution of HIV diagnosis and social determinants of health (SDH) among US-born and non-US-born Hispanic/Latino adults in the United States and Puerto Rico. METHODS: We used data reported to the Centers for Disease Control and Prevention's National HIV Surveillance System (NHSS) to determine US census tract-level HIV diagnosis rates and percentages among US-born and non-US-born Hispanic/Latino adults aged ≥18 for 2017. We merged data from the US Census Bureau's American Community Survey with NHSS data to examine regional differences in federal poverty level, education, median household income, employment, and health insurance coverage among 8648 US-born (n = 3328) and non-US-born (n = 5320) Hispanic/Latino adults. RESULTS: A comparison of US-born and non-US-born men by region showed similar distributions of HIV diagnoses. The largest percentages occurred in census tracts where ≥19% of residents lived below the federal poverty level, ≥18% did not finish high school, the median household income was <$40 000 per year, ≥6% were unemployed, and ≥16% did not have health insurance. A comparison of US-born and non-US-born women by region showed similar distributions. CONCLUSION: The findings of higher numbers of HIV diagnoses among non-US-born Hispanic/Latino adults than among US-born Hispanic/Latino adults, regional similarities in patterns of SDH and HIV percentages and rates, and Hispanic/Latino adults faring poorly in each SDH category are important for understanding SDH barriers that may be affecting Hispanic/Latino adults with HIV in the United States.


Assuntos
Mapeamento Geográfico , Infecções por HIV/diagnóstico , Hispânico ou Latino/estatística & dados numéricos , Determinantes Sociais da Saúde/estatística & dados numéricos , Adolescente , Adulto , Feminino , Infecções por HIV/economia , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Porto Rico/epidemiologia , Fatores de Risco , Estados Unidos/epidemiologia
20.
Front Public Health ; 8: 507024, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194936

RESUMO

Abnormal vaginal microbiota (AVM), including bacterial vaginosis (BV), is caused by a microbiota imbalance. Nugent scoring is the gold standard for the laboratory diagnosis of BV; however, it is somewhat subjective to interpret, and challenging to distinguish bacteria. Hence, there is a need for improved technologies for the accurate diagnosis of AVM. To this end, next-generation sequencing (NGS) technology has been shown to yield comprehensive information on the pathophysiology of AVM. Hence, to evaluate the relationship between microbiota composition and the pathophysiology of AVM and its clinical significance, we characterized vaginal swab samples from 212 pregnant Korean women using both Nugent scoring and NGS analysis. Of these, the Nugent scoring identified 175 subjects (82.5%; 175/212) with normal flora (NF), 20 (9.4%; 20/212) with intermediate flora (IF), and 17 (8.0%; 17/212) with BV. NGS analysis followed by the characterization of vaginal microbiota composition, as represented by alpha and beta diversity, revealed the relative abundance of specific bacterial taxa at the genus and species level. Moreover, we identified all five predominant community state types (CSTs) along with three smaller CSTs. Analysis of the vaginal microbiota revealed the dominance of one or two Lactobacillus spp. in the NF group. Meanwhile, the IF and BV groups were dominated by the genera Gardnerella, Prevotella, and Atopobium. These two groups also showed higher alpha diversity than the NF group (p < 0.05). Principal coordinate analysis (PCoA) indicated that the NF group was significantly different from the AVM groups (p < 0.05), whereas no significant difference was observed between IF and BV groups (p = 0.25). Lastly, to investigate the characteristics of vaginal microbiota based on taxonomic composition, the IF and BV groups (AVM groups) were reclassified using the unweighted pair group method with arithmetic mean (UPGMA) clustering. Consequently, they were reclassified into BV1 (Lactobacillus iners-dominated), BV2-1 (Bifidobacterium breve-dominated), BV2-2 (Gardnerella vaginalis s1 or s2 and Atopobium vaginae-dominated), and BV3 [mixed population of G. vaginalis, L. iners, and other bacteria (p < 0.05)]. Collectively, these findings could serve to advance the current understanding regarding AVM pathophysiology.


Assuntos
Lactobacillus , Microbiota , Actinobacteria , Feminino , Humanos , Microbiota/genética , Gravidez , República da Coreia/epidemiologia
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