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1.
J Fluoresc ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38492176

RESUMO

In this paper, a new class of two component white light emitting systems viz, JaB (java plum + beetroot) {I}, and CaB (carrot + beetroot) {II} were developed through resonance energy transfer (RET) phenomenon by using a fruit (java plum) and two vegetable (carrot and beetroot) extracts. In these white light emitting systems, java plum and carrot are the donors while beetroot is the acceptor. The primary fluorescent pigments present in the natural extracts (i.e., anthocyanin in java plum, ß-carotene in carrot, and betanin in beetroot) were responsible for the white light emission. The CIE (Commission Internationale d'Eclairage) coordinates for I and II were {0.32, 0.34} and {0.33, 0.33}, respectively, in solution phase. Interestingly, the white light emission (WLE) was also achieved in agar-agar gel medium. In gel medium, the CIE values were {0.31, 0.34} and {0.33, 0.32} for I and II, respectively. The donor-acceptor distance (r) for I and II were found to be 0.5 and 0.4 nm, respectively. Furthermore, the rate of energy transfer was also quantified with the values of 2.78 × 109 s-1 for JaB (I) and 1.02 × 108 s-1 for CaB (II) systems. The mechanistic investigation of the two white light systems was further supported by DFT studies.

2.
Leukemia ; 38(1): 82-95, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38007585

RESUMO

We identified activin A receptor type I (ACVR1), a member of the TGF-ß superfamily, as a factor favoring acute myeloid leukemia (AML) growth and a new potential therapeutic target. ACVR1 is overexpressed in FLT3-mutated AML and inhibition of ACVR1 expression sensitized AML cells to FLT3 inhibitors. We developed a novel ACVR1 inhibitor, TP-0184, which selectively caused growth arrest in FLT3-mutated AML cell lines. Molecular docking and in vitro kinase assays revealed that TP-0184 binds to both ACVR1 and FLT3 with high affinity and inhibits FLT3/ACVR1 downstream signaling. Treatment with TP-0184 or in combination with BCL2 inhibitor, venetoclax dramatically inhibited leukemia growth in FLT3-mutated AML cell lines and patient-derived xenograft models in a dose-dependent manner. These findings suggest that ACVR1 is a novel biomarker and plays a role in AML resistance to FLT3 inhibitors and that FLT3/ACVR1 dual inhibitor TP-0184 is a novel potential therapeutic tool for AML with FLT3 mutations.


Assuntos
Leucemia Mieloide Aguda , Humanos , Simulação de Acoplamento Molecular , Mutação , Linhagem Celular Tumoral , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/uso terapêutico , Apoptose , Receptores de Ativinas Tipo I/genética , Receptores de Ativinas Tipo I/uso terapêutico
3.
J Phys Chem B ; 127(49): 10529-10541, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38018428

RESUMO

A highly fluorescent, red-emitting rhodamine-based imidazolium ionic liquid (RhB-IL) was synthesized, and its structure was extensively verified using various spectroscopic techniques. The novel molecule showed exceptional selectivity toward Hg2+ ions over other competitive metal ions. Additionally, inspired by the solution results, a paper-based device was fabricated by embedding RhB-IL on paper strips and tested for the on-site detection of Hg2+ ions using a portable UV light source. Significantly, the device displayed excellent PL sensing behavior toward Hg2+ with a detection limit of 0.21 nM. In addition, RhB-IL showed the phenomena of aggregation-induced enhanced emission. In fact, when compared to the pure THF solution of RhB-IL, a remarkable 7.7-fold increase in PL intensity was seen for the 90% water fraction. Evidently, this is the first report of a paper-based Hg2+ detection system that uses a red fluorescent ionic liquid.

4.
S D Med ; 76(suppl 6): s21, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37732921

RESUMO

INTRODUCTION: Attention-deficit hyperactivity disorder (ADHD) increases the risk for comorbid psychiatric and substance use disorders, which may increase the risk of adverse patient outcomes. This study examined the prevalence of ADHD in residential addiction treatment as well as the prevalence of mono-substance use, comorbid substance use, and polysubstance use disorders (PUD) as a function of ADHD status. METHODS: All participants were adults (18 years and older) admitted to a residential substance use disorder treatment center in Sioux Falls, SD. Participants were administered a Wender Utah ADHD rating scale to assess ADHD status using a cutoff score of 46. The participants were administered ADHD questionnaires developed to assess ADHD history, family history, and academic performance. RESULTS: Students showed a 17% increase in confidence in discussing substance use with patients and a 47% increase in confidence in applying MI techniques after the instructional session. At CC, 54.5% of patients reported substance use and 16.7% of those patients responded that they would consider quitting in the next month after the student interview. In the post-clinic survey, students rated an average of 4.21 out of 5 on comfort level in discussing excessive substance use. CONCLUSION: ADHD and substance use disorder have notable comorbidity. This study demonstrates a high prevalence of ADHD in populations with substance use disorder. The presence of ADHD may be a risk factor for PUD. Effective screening and treatment of ADHD may alleviate substance use burden among users.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Comportamento Aditivo , Adulto , Humanos , Estudos Transversais , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Hospitalização , Fatores de Risco
5.
S D Med ; 76(7): 305-308, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37733961

RESUMO

Cytochrome P450 polymorphisms have gathered much attention regarding personalized psychopharmacological care. It is well documented that these drug metabolizing enzymes lead to interpatient variability in pharmacokinetic profiles. It appears that less functional genotype may increase of risk of higher side-effect burden. Here we highlight the importance of genetic polymorphisms to potentially predict a toxicity related phenotype after an intentional overdose. Genotyping may have a role in predicting serious side effects to help clinicians educate patients and their families, and implement more intensive monitoring and institute prophylactic treatment as needed.


Assuntos
Overdose de Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Melatonina , Humanos , Fluoxetina/efeitos adversos , Sistema Enzimático do Citocromo P-450/genética , Polimorfismo Genético , Convulsões
6.
Int J STD AIDS ; 34(6): 416-422, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36825555

RESUMO

BACKGROUND: Studies show that stressful life events (SLE) (e.g., discrimination, financial problems) can lead to psychosocial problems and exacerbate condomless anal sex (CAS) without protection via pre-exposure prophylaxis (PrEP) among men who have sex with men. However, few studies have examined this relationship among men who have sex with men in India, and none have examined this longitudinally. METHODS: As a part of an HIV-prevention intervention, 608 MSM from Chennai and Mumbai, India, completed behavioral surveys at baseline, 4, 8, and 12 months. We used longitudinal generalized estimating equations (GEE) modeling to examine the relationship between SLE and its severity and subsequent psychosocial problems, CAS, and history of diagnosed sexually transmitted infection (STI). All models are adjusted for age, sexual identity, intervention arm, human immunodeficiency virus status, and recruitment city. RESULTS: The number of SLE and their corresponding perceived impact score remained consistent at each time point. In multivariable GEE models, the number of SLE was predictive of CAS, depression, and harmful drinking. Similarly, the ratio of the impact of SLE was predictive of CAS, depression, and diagnosed STI. However, harmful drinking was not predictive in this model. CONCLUSIONS: These findings provide evidence that can inform future interventions, which can be used to enhance self-acceptance, coping skills, and other forms of resiliency.


Assuntos
Alcoolismo , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Humanos , Masculino , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Índia/epidemiologia , Comportamento Sexual , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Estresse Psicológico
7.
J Contemp Brachytherapy ; 15(6): 391-398, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38230402

RESUMO

Purpose: This survey aimed to understand the practice pattern and attitude of Indian doctors towards prostate brachytherapy. Material and methods: A 21-point questionnaire was designed in Google form and sent to radiation oncologists practicing in India, using texts, mails, and social media. Responses were collated, and descriptive statistical analysis was performed. Results: A total of 212 radiation oncologists from 136 centers responded to the survey questionnaire, with majority (66%) being post-specialty training > 6 years. We found that about 44.3% (n = 94) of respondents do not practice interstitial brachytherapy for any site, and majority (83.3%, n = 175) do not practice high-dose-rate (HDR) prostate brachytherapy. Only 2.8% (n = 6) of doctors preferred boost by brachytherapy compared with 38.1% (n = 80) of respondents, who favored stereotactic body radiation therapy (SBRT) boost. When asked about the indication of HDR prostate brachytherapy in Indian setting, 32.5% (n = 67) of respondents favored monotherapy, 46.1% (n = 95) of oncologists thought boost as a good indication, and 21.4% (n = 44) preferred re-irradiation/salvage setting. The most cited reason for prostate brachytherapy not being popularly practiced in India was lack of training (84.8%, n = 179). It was also noted that out of 80 respondents who practiced SBRT for prostate boost, 37 would prefer HDR brachytherapy boost if given adequate training and facilities. Conclusions: The present survey provided insight on practice of prostate brachytherapy in India. It is evident that majority of radiation oncologists do not practice HDR prostate brachytherapy due to lack of training and infrastructure. Indian physicians are willing to learn and start prostate brachytherapy procedures if dedicated training and workshops are organized.

8.
Nanotechnology ; 34(8)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36368025

RESUMO

Nowadays, the greener pathways for the synthesis of nanostructures are being explored. The extracts of different parts of plantsvizleaves, stems, and roots have been investigated. However, these extracts have been prepared by simply boiling or microwaving, or sonicating the parts of plants with water. Therefore, to have deeper insight and to investigate the full potential of plant extracts, serial extraction of leaves of sea buckthorn (Hippophae rhamnoides L.) which is a medicinally important plant was attempted using the soxhlet apparatus. The as-obtained polyphenolic-rich extract was employed for the preparation of silver nanoparticles (Ag-NPs). Under optimized reaction conditionsviz60 °C temperature and 500µl of extract solution (5 mg ml-1) highly disperse spherical nanoparticles of the average size of 15.8 ± 4.8 nm were obtained. Further, the optical band gap of Ag-NPs prepared using optimized reaction conditions was found to be 2.6 eV using the Tauc equation. Additionally, to understand the reduction by the extract, kinetic studies were also carried out which suggest the predominant occurrence of pseudo-first-order reaction. Furthermore, the mechanism of formation of Ag-NPs using major components of extractvizgallic acid and catechin which were identified by HPLC were also investigated using DFT. The mechanistic investigation was performed for both the keto-enol and radical-mediated preparation of Ag-NPs. Such theoretical investigations will help in the efficient designing of greener and novel routes for the synthesis of Ag-NPs. Additionally, the prepared silver was also employed for the colorimetric detection of H2O2.


Assuntos
Hippophae , Nanopartículas Metálicas , Prata , Cinética , Peróxido de Hidrogênio
9.
S D Med ; 75(6): 246-248, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36206563

RESUMO

Catatonia in the pediatric population is a historically overlooked syndrome. Accurate recognition is complicated by a broad differential diagnosis and co-morbid substance use, particularly in adolescent patients. Prompt treatment is vital to avoid life-threatening complications such as malignant catatonia. This article summarizes a case of relapsing adolescent catatonia and discusses the pathway of diagnosis and treatment.


Assuntos
Catatonia , Eletroconvulsoterapia , Adolescente , Catatonia/complicações , Catatonia/diagnóstico , Catatonia/terapia , Criança , Diagnóstico Diferencial , Humanos , Síndrome
10.
S D Med ; 75(4): 176-180, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35709350

RESUMO

Substance use is a major cause of morbidity and mortality in the U.S., and data from treatment centers shows that 75 percent of patients initiated their use prior to the age of 17 years. Substance use in the adolescent years affects brain development and leads to poor physical and psychiatric health, decreased academic performance, and forensic outcomes. Screening at both primary care and specialty visits allows for early intervention and treatment. This article reviews the available screening tools for substance use disorders in children and adolescents for use in a variety of clinical settings.


Assuntos
Transtornos Relacionados ao Uso de Substâncias , Adolescente , Criança , Humanos , Programas de Rastreamento , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
11.
BMC Complement Med Ther ; 22(1): 114, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35459166

RESUMO

BACKGROUND: Viral infections have a history of abrupt and severe eruptions through the years in the form of pandemics. And yet, definitive therapies or preventive measures are not present. Herbal medicines have been a source of various antiviral compounds such as Oseltamivir, extracted using shikimic acid from star anise (Illicium verum) and Acyclovir from Carissa edulis are FDA (Food and Drug Administration) approved antiviral drugs. In this study, we dissect the anti-coronavirus infection activity of Cissampelos pareira L (Cipa) extract using an integrative approach. METHODS: We analysed the signature similarities between predicted antiviral agents and Cipa using the connectivity map ( https://clue.io/ ). Next, we tested the anti-SARS-COV-2 activity of Cipa in vitro. Molecular docking analyses of constituents of with key targets of SARS-CoV2 protein viz. spike protein, RNA­dependent RNA­polymerase (RdRp) and 3C­like proteinase. was also performed. A three-way comparative analysis of Cipa transcriptome, COVID-19 BALF transcriptome and CMAP signatures of small compounds was also performed. RESULTS: Several predicted antivirals showed a high positive connectivity score with Cipa such as apcidin, emetine, homoharringtonine etc. We also observed 98% inhibition of SARS-COV-2 replication in infected Vero cell cultures with the whole extract. Some of its prominent pure constituents e.g. pareirarine, cissamine, magnoflorine exhibited 40-80% inhibition. Comparison of genes between BALF and Cipa showed an enrichment of biological processes like transcription regulation and response to lipids, to be downregulated in Cipa while being upregulated in COVID-19. CMAP also showed that Triciribine, torin-1 and VU-0365114-2 had positive connectivity with BALF 1 and 2, and negative connectivity with Cipa. Amongst all the tested compounds, Magnoflorine and Salutaridine exhibited the most potent and consistent strong in silico binding profiles with SARS-CoV2 therapeutic targets.


Assuntos
Tratamento Farmacológico da COVID-19 , Cissampelos , Antivirais/farmacologia , Cissampelos/química , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , RNA Viral , SARS-CoV-2
12.
Ann N Y Acad Sci ; 1508(1): 35-53, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34596246

RESUMO

Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by lack of hormone receptor expression and is known for high rates of recurrence, distant metastases, and poor clinical outcomes. TNBC cells lack targetable receptors; hence, there is an urgent need for targetable markers for the disease. Breast cancer stem-like cells (BCSCs) are a fraction of cells in primary tumors that are associated with tumorigenesis, metastasis, and resistance to chemotherapy. Targeting BCSCs is thus an effective strategy for preventing cancer metastatic spread and sensitizing tumors to chemotherapy. The CD44hi CD24lo phenotype is a well-established phenotype for identification of BCSCs, but CD44 and CD24 are not targetable markers owing to their expression in normal tissues. The ganglioside GD2 has been shown to be upregulated in primary TNBC tumors compared with normal breast tissue and has been shown to identify BCSCs. In this review, we discuss GD2 as a BCSC- and tumor-specific marker in TNBC; epithelial-to-mesenchymal transition and the signaling pathways that are upstream and downstream of GD2 and the role of these pathways in tumorigenesis and metastasis in TNBC; direct and indirect approaches for targeting GD2; and ongoing clinical trials and treatments directed against GD2 as well as future directions for these strategies.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinogênese , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Gangliosídeos/uso terapêutico , Células-Tronco Neoplásicas , Neoplasias de Mama Triplo Negativas , Carcinogênese/metabolismo , Carcinogênese/patologia , Feminino , Humanos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
13.
Br J Cancer ; 126(4): 615-627, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34811508

RESUMO

BACKGROUND: Metabolic stress resulting from nutrient deficiency is one of the hallmarks of a growing tumour. Here, we tested the hypothesis that metabolic stress induces breast cancer stem-like cell (BCSC) phenotype in triple-negative breast cancer (TNBC). METHODS: Flow cytometry for GD2 expression, mass spectrometry and Ingenuity Pathway Analysis for metabolomics, bioinformatics, in vitro tumorigenesis and in vivo models were used. RESULTS: Serum/glucose deprivation not only increased stress markers but also enhanced GD2+ BCSC phenotype and function in TNBC cells. Global metabolomics profiling identified upregulation of glutathione biosynthesis in GD2high cells, suggesting a role of glutamine in the BCSC phenotype. Cueing from the upregulation of the glutamine transporters in primary breast tumours, inhibition of glutamine uptake using small-molecule inhibitor V9302 reduced GD2+ cells by 70-80% and BCSC characteristics in TNBC cells. Mechanistic studies revealed inhibition of the mTOR pathway and induction of ferroptosis by V9302 in TNBC cells. Finally, inhibition of glutamine uptake significantly reduced in vivo tumour growth in a TNBC patient-derived xenograft model using NSG (non-obese diabetic/severe combined immunodeficiency with a complete null allele of the IL-2 receptor common gamma chain) mice. CONCLUSION: Here, we show metabolic stress results in GD2+ BCSC phenotype in TNBC and glutamine contributes to GD2+ phenotype, and targeting the glutamine transporters could complement conventional chemotherapy in TNBC.


Assuntos
Glicemia/análise , Gangliosídeos/metabolismo , Glutamina/metabolismo , Células-Tronco Neoplásicas/metabolismo , Bibliotecas de Moléculas Pequenas/administração & dosagem , Neoplasias de Mama Triplo Negativas/patologia , Animais , Linhagem Celular Tumoral , Feminino , Ferroptose/efeitos dos fármacos , Humanos , Metabolômica/métodos , Camundongos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Fenótipo , Bibliotecas de Moléculas Pequenas/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
S D Med ; 74(8): 372-375, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34461003

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is a commonly encountered diagnosis in the child and adolescent populations, and stimulant medications are often prescribed for their treatment. There are numerous available options in this category, including immediate and extended release formulations. There have been many case reports in the literature involving purposeful overdose on immediate release stimulants, but a relative paucity involving extended release forms. Additionally, they often involve Caucasian and Asian populations. We treated a Native American adolescent who took an overdose of extended-release methylphenidate with the intention of suicide. He developed transient orofacial dyskinesia and upper extremity choreoathetosis as a result which did not abate during his time in the emergency department. Once transferred to our care, he was given a one-time benzodiazepine dose with some benefit. This case report describes objective sequelae of a long-acting methylphenidate overdose as well as treatment for the benefit of treating clinicians with similar patient populations and situations.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Discinesias , Metilfenidato , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Criança , Discinesias/tratamento farmacológico , Humanos , Masculino , Metilfenidato/efeitos adversos , Extremidade Superior
16.
Med J Armed Forces India ; 77: S379-S384, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34334907

RESUMO

BACKGROUND: The immune response after SARS-CoV-2 is complex and may be affected by severity of the disease, race, etc. The present study was conducted to assess the serial antibody response among the COVID-19 patients admitted in the hospital. METHODS: The study was conducted between July and October 2020 in a dedicated COVID-19 hospital. All consented patients underwent serial testing of antibodies using a rapid chromatographic immunoassay-based qualitative IgG/IgM kit every third day until their discharge or death. The data about age, sex, severity of disease, length of stay, onset of symptoms, date of molecular testing were also collected. Appropriate statistical tests were used. RESULTS: The mean age of 1000 COVID-19 patients was 47.5 ± 17.9 years. Out of the total, 687 (68.7%) were males. With respect to severity, 682 (68.2%) were asymptomatic/mild, 200 (20%) were moderate and 118 (11.8%) were severe cases. The seroconversion percentage increased from 12.8% to 97.9% and 16.3% to 80.9% for IgG and IgM respectively in 21 days. The median time for seroconversion was 10 days (IQR:6-12 days) for IgG and eight days (IQR: 6-11 days) for IgM. At the time of discharge (median nine days), detectable IgG and IgM antibodies were present in 502 (52.46%) and 414 (43.26%) participants respectively. Seroconversion was associated with days after the symptoms, increasing severity of the disease and the presence of co-morbidity. CONCLUSION: Seroconversion increased during the period of observation. The severe/moderate cases of COVID-19 tend to have an early seroconversion as compared to the asymptomatic/mild cases. Only half of the patients were seroconverted at discharge.

17.
Mol Cell Biochem ; 476(11): 3935-3950, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34181183

RESUMO

Extracellular matrix (ECM) plays an important role in the structural organization of tissue and delivery of external cues to the cell. Biglycan, a class I small leucine-rich proteoglycans (SLRP), is a key component of the ECM that participates in scaffolding the collagen fibrils and mediates cell signaling. Dysregulation of biglycan expression can result in wide range of clinical conditions such as metabolic disorder, inflammatory disorder, musculoskeletal defects and malignancies. In this review, we aim to update our current understanding regarding the link between altered expression of biglycan and different clinicopathological states. Biglycan interacts with toll like receptors (TLR)-2 and TLR-4 on the immune cells which initiates inflammation and aggravates inflammatory disorders. ECM unbound soluble biglycan acts as a DAMP (danger associated molecular pattern) resulting in sterile inflammation. Dysregulation of biglycan expression is also observed in inflammatory metabolic conditions such as atherosclerosis and obesity. In cancer, high-biglycan expression facilitates tumor growth, invasion and metastasis which is associated with poor clinical outcome. As a pivotal structural component of the ECM, biglycan strengthens the musculoskeletal system and its absence is associated with musculoskeletal defects. Thus, SLRP biglycan is a potential marker which is significantly altered in different clinicopathological states.


Assuntos
Biglicano/metabolismo , Inflamação/imunologia , Doenças Metabólicas/imunologia , Neoplasias/metabolismo , Proteoglicanos Pequenos Ricos em Leucina/metabolismo , Animais , Biomarcadores/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/patologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Neoplasias/imunologia , Neoplasias/patologia , Receptor 2 Toll-Like/imunologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo
18.
S D Med ; 74(2): 76-78, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34161688

RESUMO

National epidemiological studies indicate that vaping or e-cigarette use has increased in alarming proportions among American adolescents. In vaping, a battery-powered device heats up a liquid into an aerosol which is inhaled by the user. The aerosol, commonly referred to as vapor, usually contains nicotine, flavoring, marijuana along with other chemicals and substances. This article highlights serious yet avoidable health risks from vaping amidst the coronavirus disease 2019 (COVID-19) pandemic. Vaping may mediate transmission, infections, disease progression and risk of succumbing to COVID-19. An overview of possible solutions and resources for South Dakota physicians is also discussed.


Assuntos
COVID-19 , Sistemas Eletrônicos de Liberação de Nicotina , Vaping , Adolescente , Humanos , Pandemias , SARS-CoV-2 , South Dakota/epidemiologia , Estados Unidos/epidemiologia
19.
J Immunother Cancer ; 9(3)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33722905

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no effective standard therapy. Breast cancer stem-like cells (BCSCs) in primary TNBCs are reported to be responsible for metastatic spread of the disease and resistance to chemotherapy, but no available therapeutic tools target BCSCs. We previously reported that the ganglioside GD2 is highly expressed on BCSCs and that inhibition of its expression hampers TNBC growth. We therefore hypothesized that the anti-GD2 antibody dinutuximab (ch14.18) targets GD2+ BCSCs and inhibits TNBC growth. METHOD: To test our hypothesis, we first determined GD2 expression via immunohistochemistry in frozen primary tumor samples from patients with TNBC (n=89). Then, we examined the effects of dinutuximab on TNBC cell adhesion, migration, and mammosphere formation in vitro and on tumor growth in vivo using TNBC cell-line and patient-derived xenograft (PDX) models. RESULTS: We found that GD2 was expressed in around 60% of primary TNBC tumors at variable levels and was associated with worse overall survival of patients with TNBC (p=0.002). GD2 was found to be expressed in tumors and stroma, but normal ducts and lobules in adjacent tissues have shown low or no GD2 staining, indicating that GD2 is potentially a novel biomarker for tumor and its microenvironment. Treatment with dinutuximab significantly decreased adhesion and migration of MDA-MB-231 and SUM159 TNBC cells. Moreover, dinutuximab treatment inhibited mTOR signaling, which has been shown to be regulated by GD2 in BCSCs. Dinutuximab also reduced tumor growth in nude mice bearing TNBC cell-line xenografts. Finally, dinutuximab in combination with activated natural killer cells inhibited tumor growth in a TNBC PDX model and improved overall survival of tumor-bearing mice. CONCLUSIONS: Dinutuximab successfully eliminated GD2+ cells and reduced tumor growth in both in vivo models. Our data provide proof-of-concept for the criticality of GD2 in BCSCs and demonstrate the potential of dinutuximab as a novel therapeutic approach for TNBC.


Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos Imunológicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Gangliosídeos/antagonistas & inibidores , Células-Tronco Neoplásicas/efeitos dos fármacos , Carga Tumoral/efeitos dos fármacos , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Feminino , Gangliosídeos/metabolismo , Humanos , Imunoterapia Adotiva , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/transplante , Camundongos Nus , Camundongos SCID , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Lancet Glob Health ; 9(4): e446-e455, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33740407

RESUMO

BACKGROUND: Men who have sex with men (MSM) in India are extremely marginalised and stigmatised, and therefore experience immense psychosocial stress. As current HIV prevention interventions in India do not address mental health or resilience to these stressors, we aimed to evaluate a resilience-based psychosocial intervention in the context of HIV and sexually transmitted infection (STI) prevention. METHODS: We did a multicity, randomised, clinical efficacy trial in Chennai (governmental tuberculosis research institute) and Mumbai (non-governmental organisation for MSM), India. Inclusion criteria were MSM, aged 18 years or older, who were at risk of HIV acquisition or transmission, defined as having any of the following in the 4 months before screening: anal sex with four or more male partners (protected or unprotected), diagnosis of an STI, history of transactional sex activity, or condomless anal sex with a man who was of unknown HIV status or serodiscordant. Participants were required to speak English, Tamil (in Chennai), or Hindi (in Mumbai) fluently. Eligible individuals were randomly assigned (1:1) to either a resilience-based psychosocial HIV prevention intervention, consisting of group (four sessions) and individual (six sessions) counselling alongside HIV and STI voluntary counselling and testing, or a standard-of-care control comprising voluntary counselling and testing alone. The primary outcomes were number of condomless anal sex acts with male partners during the past month (at baseline and 4 months, 8 months, and 12 months after randomisation), and incident bacterial STIs (at 12 months after randomisation). Resilience-related mediators included self-esteem, self-acceptance, and depression. Recruitment is now closed. This trial is registered with ClinicalTrials.gov, NCT02556294. FINDINGS: Between Sept 4, 2015, and June 28, 2018, we enrolled 608 participants; 305 (50%) were assigned to the psychosocial intervention condition and 303 (50%) were assigned to the control condition. 510 (84%) of 608 men completed an assessment at 4 months after randomisation, 483 (79%) at 8 months, and 515 (85%) at 12 months. 512 (99%) of 515 men had STI data from the 12-month assessment. The intervention condition had a 56% larger reduction in condomless anal sex acts (95% CI 35-71; p<0·0001) from baseline to 4-month follow-up, 72% larger reduction (56-82; p<0·0001) from baseline to 8-month follow-up, and 72% larger reduction (53-83; p<0·0001) from baseline to 12-month follow-up, compared with the standard-of-care control condition (condition by time interaction; χ2=40·29, 3 df; p<0·0001). Improvements in self-esteem and depressive symptoms both mediated 9% of the intervention effect on condomless anal sex acts. Bacterial STI incidence did not differ between study conditions at 12-month follow-up. INTERPRETATION: A resilience-based psychosocial intervention for MSM at risk of HIV acquisition or transmission in India was efficacious in reducing condomless anal sex acts, with evidence for mediation effects in two key target resilience variables. HIV prevention programmes for MSM in India should address mental health resilience to augment reductions in the risk of sexually transmitted HIV. FUNDING: National Institute of Mental Health.


Assuntos
Infecções por HIV/prevenção & controle , Reabilitação Psiquiátrica/métodos , Resiliência Psicológica , Minorias Sexuais e de Gênero/psicologia , Estigma Social , Adulto , Aconselhamento/métodos , Seguimentos , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Teste de HIV , Humanos , Índia/epidemiologia , Masculino , Comportamento de Redução do Risco , Comportamento Sexual/psicologia , Resultado do Tratamento , Sexo sem Proteção/prevenção & controle , Sexo sem Proteção/psicologia , Adulto Jovem
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