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1.
Bol. latinoam. Caribe plantas med. aromát ; 23(4): 577-607, jul. 2024. ilus, graf, tab
Artigo em Espanhol | LILACS | ID: biblio-1538069

RESUMO

El presente estudio es una comparación del dolor abdominal producido por trastornos gastrointestinales, aliviado por Ageratina ligustrina , entre los grupos maya Tzeltal, Tzotzil y Q ́eqchi ́, el cual integró un enfoque etnomédico, etnobotánico y transcultural, comparando estudios previos con el presente trabajo de campo. Para evaluar la eficacia de Ageratina para aliviar el dolor abdominal, se realizó un inventario de las moléculas reportadas en esta especie, así como de su actividad farmacológica, a través de una revisión bibliográfica. Los resultados mostraron que la epidemiología del dolor producido por TGI, su etnobotánica y el modelo explicativo del dolor abdominal fueron similares entre grupos étnicos. Asimismo, se identificaron 27 moléculas con efectos antiinflamatorios y antinociceptivos, lo que podría explicar por qué esta especie es culturalmente importante para los pobladores maya Tzeltal, Tzotzil y Q ́eqch i ́ para el alivio del dolor abdominal, mientras que, desde el punto de vista biomédico, es una especie con potencial para inhibir el dolor visceral.


The current study is a comparison of the abdominal pain conception produced by gastrointestinal disorders, relieved by Ageratina ligustrina , among inhabitants of the Mayan Tzeltal, Tzotzil, and Q'eqchi' groups ethnomedical, ethnobotanical, and cross -cultural approaches were used to compare previous studies with the present field work. To evaluate the efficacy of A. ligustrina to relieve pain, also through a bibliographic review an inventory of the molecules present in this species was performed, as well as their pharmacological activity. The results showed that the epidemiology of pain produced by GID, its ethnobotany, and the explanatory model of abdominal pain are similar among ethnic groups. Likewise, 27 molecules with anti-inflammatory and anti-nociceptive effects were identified, which could explain why this species is culturally important for the Mayan Tzeltal, Tzotzil, and Q'eqchi' groups for the relief of abdominal pain, while, from a biomedical point of view, it is a species with potential to inhibit visceral pain.


Assuntos
Extratos Vegetais/uso terapêutico , Dor Abdominal/tratamento farmacológico , Ageratina , Etnobotânica , Gastroenteropatias/tratamento farmacológico , México
2.
J Ethnopharmacol ; 330: 118264, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38692417

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Optimized New Shengmai Powder (ONSMP) is a sophisticated traditional Chinese medicinal formula renowned for bolstering vital energy, optimizing blood circulation, and mitigating fluid retention. After years of clinical application, ONSMP has shown a significant impact in improving myocardial injury and cardiac function and has a positive effect on treating heart failure. However, many unknowns exist about the molecular biological mechanisms of how ONSMP exerts its therapeutic effects, which require further research and exploration. AIM OF THE STUDY: Exploring the potential molecular biological mechanisms by which ONSMP ameliorates cardiomyocyte apoptosis and ferroptosis in ischemic heart failure (IHF). MATERIALS AND METHODS: First, we constructed a rat model of IHF by inducing acute myocardial infarction through surgery and using echocardiography, organ coefficients, markers of heart failure, antioxidant markers, and histopathological examination to assess the effects of ONSMP on cardiomyocyte apoptosis and ferroptosis in IHF rats. Next, we used bioinformatics analysis techniques to analyze the active components, signaling pathways, and core targets of ONSMP and calculated the interactions between core targets and corresponding elements. Finally, we detected the positive expression of apoptosis and ferroptosis markers and core indicators of signaling pathways by immunohistochemistry; detected the mean fluorescence intensity of core indicators of signaling pathways by immunofluorescence; detected the protein expression of signaling pathways and downstream effector molecules by western blotting; and detected the mRNA levels of p53 and downstream effector molecules by quantitative polymerase chain reaction. RESULTS: ONSMP can activate the Ser83 site of ASK by promoting the phosphorylation of the PI3K/AKT axis, thereby inhibiting the MKK3/6-p38 axis and the MKK4/7-JNK axis signaling to reduce p53 expression, and can also directly target and inhibit the activity of p53, ultimately inhibiting p53-mediated mRNA and protein increases in PUMA, SAT1, PIG3, and TFR1, as well as mRNA and protein decreases in SLC7A11, thereby inhibiting cardiomyocyte apoptosis and ferroptosis, effectively improving cardiac function and ventricular remodeling in IHF rat models. CONCLUSION: ONSMP can inhibit cardiomyocyte apoptosis and ferroptosis through the PI3K/AKT/p53 signaling pathway, delaying the development of IHF.


Assuntos
Apoptose , Combinação de Medicamentos , Medicamentos de Ervas Chinesas , Ferroptose , Insuficiência Cardíaca , Miócitos Cardíacos , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Transdução de Sinais , Proteína Supressora de Tumor p53 , Animais , Ferroptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Apoptose/efeitos dos fármacos , Masculino , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Ratos , Fosfatidilinositol 3-Quinase/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Modelos Animais de Doenças , Pós
3.
Cancer Immunol Immunother ; 73(6): 113, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38693312

RESUMO

Senescent cells have a profound impact on the surrounding microenvironment through the secretion of numerous bioactive molecules and inflammatory factors. The induction of therapy-induced senescence by anticancer drugs is known, but how senescent tumor cells influence the tumor immune landscape, particularly neutrophil activity, is still unclear. In this study, we investigate the induction of cellular senescence in breast cancer cells and the subsequent immunomodulatory effects on neutrophils using the CDK4/6 inhibitor palbociclib, which is approved for the treatment of breast cancer and is under intense investigation for additional malignancies. Our research demonstrates that palbociclib induces a reversible form of senescence endowed with an inflammatory secretome capable of recruiting and activating neutrophils, in part through the action of interleukin-8 and acute-phase serum amyloid A1. The activation of neutrophils is accompanied by the release of neutrophil extracellular trap and the phagocytic removal of senescent tumor cells. These findings may be relevant for the success of cancer therapy as neutrophils, and neutrophil-driven inflammation can differently affect tumor progression. Our results reveal that neutrophils, as already demonstrated for macrophages and natural killer cells, can be recruited and engaged by senescent tumor cells to participate in their clearance. Understanding the interplay between senescent cells and neutrophils may lead to innovative strategies to cope with chronic or tumor-associated inflammation.


Assuntos
Neoplasias da Mama , Senescência Celular , Neutrófilos , Piperazinas , Piridinas , Humanos , Piperazinas/farmacologia , Piridinas/farmacologia , Senescência Celular/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Neutrófilos/metabolismo , Neutrófilos/imunologia , Neutrófilos/efeitos dos fármacos , Linhagem Celular Tumoral , Ativação de Neutrófilo/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
4.
G Ital Nefrol ; 41(2)2024 Apr 29.
Artigo em Italiano | MEDLINE | ID: mdl-38695225

RESUMO

Patients affected by heart failure (HF) with reduced ejection fraction (HFrEF) are prone to experience episodes of worsening symptoms and signs despite continued therapy, termed "worsening heart failure" (WHF). Although guideline-directed medical therapy is well established, worsening of chronic heart failure accounts for almost 50% of all hospital admissions for HF with consequent higher risk of death and hospitalization than patients with "stable" HF. New drugs are emerging as cornerstones to reduce residual risk of both cardiovascular mortality and readmission for heart failure. The following review will debate about emerging definition of WHF in light of the recent clinical consensus released by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) and the new therapeutic strategies in cardiorenal patients.


Assuntos
Insuficiência Cardíaca , Volume Sistólico , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Progressão da Doença , Guias de Prática Clínica como Assunto , Neurotransmissores/uso terapêutico
5.
Arq Bras Cardiol ; 121(3): e20230470, 2024.
Artigo em Português, Inglês | MEDLINE | ID: mdl-38695466

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with hypercoagulability. It remains uncertain whether ongoing anticoagulation for atrial fibrillation (AF) in patients who later contract COVID-19 improves clinical outcomes. OBJECTIVES: To compare chronic oral anticoagulation with no previous anticoagulation in patients with AF who contracted a COVID-19 infection concerning the outcomes of all-cause mortality, COVID-19 mortality, intensive care unit (ICU) admission, and hospitalization. METHODS: We systematically searched PubMed, Embase, and Cochrane Library for eligible studies from inception to December 2022. We included studies comparing COVID-19 outcomes in patients with versus without prior chronic anticoagulation for AF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random-effects model. The level of significance was set at p < 0.05. Quality assessment and risk of bias were performed according to Cochrane recommendations. RESULTS: Ten studies comprising 1,177,858 patients with COVID-19 and AF were identified, of whom 893,772 (75.9%) were on prior chronic anticoagulation for AF. In patients with COVID-19, being on chronic anticoagulation for AF significantly reduced all-cause mortality (RR 0.75; 95% CI 0.57 to 0.99; p = 0.048; I2 = 89%) and COVID-19-related mortality (RR 0.76; 95% CI 0.72 to 0.79; p < 0.001; I2 = 0%) when compared with no prior anticoagulation. In contrast, there was no difference between groups regarding hospitalization (RR 1.08; 95% CI 0.82 to 1.41; p = 0.587; I2 = 95%) or ICU admission (RR 0.86; 95% CI 0.68 to 1.09; p = 0.216; I2 = 69%). CONCLUSIONS: In this meta-analysis, chronic anticoagulation for patients with AF who contracted COVID-19 was associated with significantly lower rates of all-cause mortality and COVID-19-related mortality as compared with no previous anticoagulation.


FUNDAMENTO: A doença por coronavírus 2019 (COVID-19) está associada à hipercoagulabilidade. Permanece incerto se a anticoagulação contínua para fibrilação atrial (FA) em pacientes que posteriormente contraem COVID-19 melhora os desfechos clínicos. OBJETIVOS: Comparar a anticoagulação oral crônica com ausência de anticoagulação prévia em pacientes com FA que contraíram uma infecção por COVID-19 em relação aos desfechos de mortalidade por todas as causas, mortalidade por COVID-19, admissão em unidade de terapia intensiva (UTI) e hospitalização. MÉTODOS: Buscamos sistematicamente no PubMed, Embase e Cochrane Library estudos elegíveis desde o início até dezembro de 2022. Incluímos estudos que compararam desfechos de COVID-19 em pacientes com e sem anticoagulação crônica prévia para FA. Foram agrupadas razões de risco (RR) com intervalos de confiança (IC) de 95% por meio de um modelo de efeitos aleatórios. O nível de significância foi estabelecido em p < 0,05. As avaliações da qualidade e do risco de viés foram realizadas de acordo com as recomendações da Cochrane. RESULTADOS: Foram identificados 10 estudos abrangendo 1.177.858 pacientes com COVID-19 e FA, dos quais 893.772 (75,9%) estavam em anticoagulação crônica prévia para FA. Em pacientes com COVID-19, a anticoagulação crônica para FA reduziu significativamente a mortalidade por todas as causas (RR 0,75; IC 95% 0,57 a 0,99; p = 0,048; I2 = 89%) e a mortalidade relacionada à COVID-19 (RR 0,76; IC 95% 0,72 a 0,79; p < 0,001; I2 = 0%) quando comparada com a ausência de anticoagulação prévia. Em contrapartida, não houve diferença entre os grupos em relação à hospitalização (RR 1,08; IC 95% 0,82 a 1,41; p = 0,587; I2 = 95%) ou internação em UTI (RR 0,86; IC 95% 0,68 a 1,09; p = 0,216; I2 = 69%). CONCLUSÕES: Nesta metanálise, a anticoagulação crônica para pacientes com FA que contraíram COVID-19 foi associada a taxas significativamente mais baixas de mortalidade por todas as causas e mortalidade relacionada à COVID-19 em comparação com a ausência de anticoagulação anterior.


Assuntos
Anticoagulantes , Fibrilação Atrial , COVID-19 , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/complicações , COVID-19/mortalidade , COVID-19/complicações , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Hospitalização/estatística & dados numéricos , SARS-CoV-2 , Unidades de Terapia Intensiva
6.
Cell Genom ; 4(5): 100550, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38697125

RESUMO

To identify novel susceptibility genes for hepatocellular carcinoma (HCC), we performed a rare-variant association study in Chinese populations consisting of 2,750 cases and 4,153 controls. We identified four HCC-associated genes, including NRDE2, RANBP17, RTEL1, and STEAP3. Using NRDE2 (index rs199890497 [p.N377I], p = 1.19 × 10-9) as an exemplary candidate, we demonstrated that it promotes homologous recombination (HR) repair and suppresses HCC. Mechanistically, NRDE2 binds to the subunits of casein kinase 2 (CK2) and facilitates the assembly and activity of the CK2 holoenzyme. This NRDE2-mediated enhancement of CK2 activity increases the phosphorylation of MDC1 and then facilitates the HR repair. These functions are eliminated almost completely by the NRDE2-p.N377I variant, which sensitizes the HCC cells to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with chemotherapy. Collectively, our findings highlight the relevance of the rare variants to genetic susceptibility to HCC, which would be helpful for the precise treatment of this malignancy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Inibidores de Poli(ADP-Ribose) Polimerases , Reparo de DNA por Recombinação , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Reparo de DNA por Recombinação/efeitos dos fármacos , Caseína Quinase II/genética , Caseína Quinase II/metabolismo , Masculino , Camundongos , Animais , Feminino , Linhagem Celular Tumoral , Pessoa de Meia-Idade , Predisposição Genética para Doença
7.
Cell ; 187(10): 2465-2484.e22, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38701782

RESUMO

Remyelination failure in diseases like multiple sclerosis (MS) was thought to involve suppressed maturation of oligodendrocyte precursors; however, oligodendrocytes are present in MS lesions yet lack myelin production. We found that oligodendrocytes in the lesions are epigenetically silenced. Developing a transgenic reporter labeling differentiated oligodendrocytes for phenotypic screening, we identified a small-molecule epigenetic-silencing-inhibitor (ESI1) that enhances myelin production and ensheathment. ESI1 promotes remyelination in animal models of demyelination and enables de novo myelinogenesis on regenerated CNS axons. ESI1 treatment lengthened myelin sheaths in human iPSC-derived organoids and augmented (re)myelination in aged mice while reversing age-related cognitive decline. Multi-omics revealed that ESI1 induces an active chromatin landscape that activates myelinogenic pathways and reprograms metabolism. Notably, ESI1 triggered nuclear condensate formation of master lipid-metabolic regulators SREBP1/2, concentrating transcriptional co-activators to drive lipid/cholesterol biosynthesis. Our study highlights the potential of targeting epigenetic silencing to enable CNS myelin regeneration in demyelinating diseases and aging.


Assuntos
Epigênese Genética , Bainha de Mielina , Oligodendroglia , Remielinização , Animais , Bainha de Mielina/metabolismo , Humanos , Camundongos , Remielinização/efeitos dos fármacos , Oligodendroglia/metabolismo , Sistema Nervoso Central/metabolismo , Camundongos Endogâmicos C57BL , Rejuvenescimento , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Organoides/metabolismo , Organoides/efeitos dos fármacos , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/genética , Diferenciação Celular/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Masculino , Regeneração/efeitos dos fármacos , Esclerose Múltipla/metabolismo , Esclerose Múltipla/genética , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/patologia
8.
S Afr Fam Pract (2004) ; 66(1): e1-e8, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38708751

RESUMO

BACKGROUND:  Transgender women bear a huge burden of human immunodeficiency virus (HIV) in South Africa. However, they are not fully engaged in healthcare across the HIV continuum of care. In addition, transgender women face multiple facets of stigma and discrimination as well as socio-economic inequalities, which all have a negative impact on antiretroviral therapy (ART) adherence. OBJECTIVE:  The study aimed at exploring and describing the experiences of ART adherence of transgender women living with HIV in the Buffalo City Metro Municipality. METHODS:  The study employed an interpretative phenomenological analysis (IPA) design. Twelve participants were enrolled using a snowballing sampling technique. Data were collected using semi-structured interviews and analysed using an IPA framework. RESULTS:  While exploring determinants to ART adherence among transgender women living with HIV in Buffalo City Metro, two superordinate themes emerged: enablers to ART adherence and psychosocial factors promoting adherence. The study found that factors such as differentiated ART service delivery, ARV medicines-related factors, motivators for taking treatment and support systems facilitated ART adherence. CONCLUSION:  Emerging from this study is the need to scale up differentiated, person-centred ART service deliveries that will enhance access and adherence to treatment for transgender women.Contribution: This study provides unique insights on factors enhancing ART adherence among transgender women. There is a paucity of literature on access to HIV care services for key and vulnerable populations, and these findings will be shared in the country and in the region.


Assuntos
Infecções por HIV , Adesão à Medicação , Pessoas Transgênero , Humanos , África do Sul , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Adesão à Medicação/psicologia , Pessoas Transgênero/psicologia , Adulto , Masculino , Estigma Social , Pesquisa Qualitativa , Fármacos Anti-HIV/uso terapêutico , Pessoa de Meia-Idade , Entrevistas como Assunto , Antirretrovirais/uso terapêutico , Adulto Jovem
9.
Curationis ; 47(1): e1-e7, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38708757

RESUMO

BACKGROUND:  The human immunodeficiency virus and acquired immunodeficiency syndrome (HIV and AIDS) pandemic has greatly affected Africa, particularly Ghana. The pandemic remains a public health concern, particularly in terms of accessing essential medication and improving quality of life for people living with the disease. OBJECTIVES:  This study aimed to explore and describe the experiences of persons diagnosed and living with HIV who are on antiretroviral therapy. METHOD:  A qualitative, exploratory, descriptive, and contextual design was used. The research population included persons diagnosed with HIV who were receiving antiretroviral therapy at three public hospitals in Ghana. Data saturation was achieved after conducting 15 semi-structured interviews. Creswell's six steps of data analysis were used to analyse the data, which resulted in the emergence of one main theme and six sub-themes. RESULTS:  The main theme identified by the researchers highlighted the participants' diverse experiences of being diagnosed and living with HIV. It was found that the study participants expressed shock, disbelief, surprise, and fear of death after being diagnosed with HIV. The participants also experienced stigmatisation, discrimination, and rejection. CONCLUSION:  There is a need for further research on the extent of discrimination and stigmatisation and the effect on optimal adherence to antiretroviral therapy. Continuous public education on HIV is required to limit the extent of discrimination and stigmatisation.Contribution: The study has highlighted the various emotions related to stigma and discrimination expressed by persons living with HIV (PLHIV). The findings will guide policy on eliminating discrimination and stigmatisation for people living with HIV.


Assuntos
Infecções por HIV , Pesquisa Qualitativa , Humanos , Gana , Feminino , Masculino , Adulto , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Pessoa de Meia-Idade , Estigma Social , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/psicologia , Entrevistas como Assunto/métodos , Antirretrovirais/uso terapêutico , Qualidade de Vida/psicologia , Fármacos Anti-HIV/uso terapêutico
10.
Arch Endocrinol Metab ; 68: e220480, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709148

RESUMO

Objective: The aim of this study was to evaluate the glycated hemoglobin (HbA1c) levels before and after sustained virologic response (SVR) and investigate the baseline characteristics associated with improved glycemic control in patients with chronic hepatitis C (CHC) achieving SVR after directacting antivirals (DAA) therapy. Materials and methods: Consecutive adult patients with CHC who achieved SVR after DAA treatment between January 2016 and December 2017 at Hospital de Clínicas de Porto Alegre (RS, Brazil) were prospectively included. Levels of HbA1c were measured up to 24 weeks before DAA therapy and 12 weeks after SVR. Exclusion criteria were decompensated cirrhosis, HIV and/or hepatitis B virus, liver disease of other etiologies, and/or modification of prediabetes/ type 2 diabetes mellitus (PDM/T2DM) management. The primary outcome was a comparison of HbA1c levels before and after SVR. Secondary outcomes were the baseline variables associated with improved glycemic control. Results: The study included 207 patients with a mean age of 60.6±10.7 years, of whom 51.7% were women, 56% had cirrhosis, 37.7% had HCV genotype 3, and 54.5% had baseline T2DM or PDM. The median HbA1c level reduced significantly after SVR (5.5%, interquartile range [IQR] 4.9%-6.3%) compared with baseline (5.7%, IQR 5.3%-6.7%; p = 0.01). The baseline characteristics associated with improved HbA1c after SVR were cirrhosis, genotype 3, and age ≤ 60 years. Conclusion: Among patients with CHC, SVR after DAA was associated with HbA1c reduction, particularly in those with cirrhosis, genotype 3, and age ≤ 60 years.


Assuntos
Antivirais , Glicemia , Hemoglobinas Glicadas , Hepatite C Crônica , Resposta Viral Sustentada , Humanos , Feminino , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/sangue , Masculino , Pessoa de Meia-Idade , Hemoglobinas Glicadas/análise , Glicemia/análise , Glicemia/efeitos dos fármacos , Idoso , Estudos Prospectivos , Resultado do Tratamento , Hepacivirus/genética , Hepacivirus/efeitos dos fármacos , Brasil , Adulto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue
11.
Physiol Res ; 73(2): 227-237, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38710058

RESUMO

Nephrotoxicity as a cause of acute kidney injury (AKI) induced by cisplatin (CP), limits its usefulness as an anticancer agent. Diminazene, an angiotensin converting enzyme 2 activator, exhibited renoprotective properties on rat models of kidney diseases. This research aims to investigate the salutary effect of diminazene in comparison with lisinopril or valsartan in CP-induced AKI. The first and second groups of rats received oral vehicle (distilled water) for 9 days, and saline injection or intraperitoneal CP (6 mg/kg) on day 6, respectively. Third, fourth, and fifth groups received intraperitoneal injections of CP on day 6 and diminazene (15 mg/kg/day, orally), lisinopril (10 mg/kg/day, orally), or valsartan (30 mg/kg/day, orally), for 9 days, respectively. 24h after the last day of treatment, blood and kidneys were removed under anesthesia for biochemical and histopathological examination. Urine during the last 24 h before sacrificing the rats was also collected. CP significantly increased plasma urea, creatinine, neutrophil gelatinase-associated lipocalin, calcium, phosphorus, and uric acid. It also increased urinary albumin/creatinine ratio, N-Acetyl-beta-D-Glucosaminidase/creatinine ratio, and reduced creatinine clearance, as well the plasma concentrations of inflammatory cytokines [plasma tumor necrosis factor-alpha, and interleukin-1beta], and significantly reduced antioxidant indices [catalase, glutathione reductase , and superoxide dismutase]. Histopathologically, CP treatment caused necrosis of renal tubules, tubular casts, shrunken glomeruli, and increased renal fibrosis. Diminazine, lisinopril, and valsartan ameliorated CP-induced biochemical and histopathological changes to a similar extent. The salutary effect of the three drugs used is, at least partially, due to their anti-inflammatory and antioxidant effects. Keywords: Cisplatin, Diminazene, ACE2 activator, Lisinopril, Valsartan, Acute kidney injury.


Assuntos
Injúria Renal Aguda , Cisplatino , Diminazena , Lisinopril , Ratos Wistar , Valsartana , Animais , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/tratamento farmacológico , Lisinopril/farmacologia , Cisplatino/toxicidade , Valsartana/farmacologia , Masculino , Diminazena/análogos & derivados , Diminazena/farmacologia , Diminazena/uso terapêutico , Ratos , Antineoplásicos/toxicidade , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo
12.
Int J Immunopathol Pharmacol ; 38: 3946320241240706, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38712735

RESUMO

Introduction: Bladder cancer represents a significant public health concern with diverse genetic alterations influencing disease onset, progression, and therapy response. In this study, we explore the multifaceted role of Solute Carrier Family 31 Member 1 (SLC31A1) in bladder cancer, a pivotal gene involved in copper homeostasis. Methods: Our research involved analyzing the SLC31A1 gene expression via RT-qPCR, promoter methylation via targeted bisulfite sequencing, and mutational status via Next Generation Sequencing (NGS) using the clinical samples sourced by the local bladder cancer patients. Later on, The Cancer Genome Atlas (TCGA) datasets were utilized for validation purposes. Moreover, prognostic significance, gene enrichment terms, and therapeutic drugs of SLC31A1 were also explored using KM Plotter, DAVID, and DrugBank databases. Results: We observed that SLC31A1 was significantly up-regulated at both the mRNA and protein levels in bladder cancer tissue samples, suggesting its potential involvement in bladder cancer development and progression. Furthermore, our investigation into the methylation status revealed that SLC31A1 was significantly hypomethylated in bladder cancer tissues, which may contribute to its overexpression. The ROC analysis of the SLC31A1 gene indicated promising diagnostic potential, emphasizing its relevance in distinguishing bladder cancer patients from normal individuals. However, it is crucial to consider other factors such as cancer stage, metastasis, and recurrence for a more accurate evaluation in the clinical context. Interestingly, mutational analysis of SLC31A1 demonstrated only benign mutations, indicating their unknown role in the SLC31A1 disruption. In addition to its diagnostic value, high SLC31A1 expression was associated with poorer overall survival (OS) in bladder cancer patients, shedding light on its prognostic relevance. Gene enrichment analysis indicated that SLC31A1 could influence metabolic and copper-related processes, further underscoring its role in bladder cancer. Lastly, we explored the DrugBank database to identify potential therapeutic agents capable of reducing SLC31A1 expression. Our findings unveiled six important drugs with the potential to target SLC31A1 as a treatment strategy. Conclusion: Our comprehensive investigation highlights SLC31A1 as a promising biomarker for bladder cancer development, progression, and therapy.


Assuntos
Transportador de Cobre 1 , Metilação de DNA , Progressão da Doença , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Transportador de Cobre 1/genética , Transportador de Cobre 1/metabolismo , Regulação Neoplásica da Expressão Gênica , Masculino , Feminino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regiões Promotoras Genéticas , Mutação , Pessoa de Meia-Idade , Prognóstico , Idoso , Regulação para Cima
13.
Int J Immunopathol Pharmacol ; 38: 3946320241250293, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38712748

RESUMO

BACKGROUND: Cell metabolism functions without a stop in normal and pathological cells. Different metabolic changes occur in the disease. Cell metabolism influences biochemical and metabolic processes, signaling pathways, and gene regulation. Knowledge regarding disease metabolism is limited. OBJECTIVE: The review examines the cell metabolism of glucose, nucleotides, and lipids during homeostatic and pathological conditions of neurotoxicity, neuroimmunological disease, Parkinson's disease, thymoma in myasthenia gravis, and colorectal cancer. METHODS: Data collection includes electronic databases, the National Center for Biotechnology Information, and Google Scholar, with several inclusion criteria: cell metabolism, glucose metabolism, nucleotide metabolism, and lipid metabolism in health and disease patients suffering from neurotoxicity, neuroinflammation, Parkinson's disease, thymoma in myasthenia gravis. The initial number of collected and analyzed papers is 250. The final analysis included 150 studies out of 94 selected papers. After the selection process, 62.67% remains useful. RESULTS AND CONCLUSION: A literature search shows that signaling molecules are involved in metabolic changes in cells. Differences between cancer and neuroimmunological diseases are present in the result section. Our finding enables insight into novel therapeutic targets and the development of scientific approaches for cancer and neurological disease onset, outcome, progression, and treatment, highlighting the importance of metabolic dysregulation. Current understanding, emerging research technologies and potential therapeutic interventions in metabolic programming is disucussed and highlighted.


Assuntos
Glucose , Metabolismo dos Lipídeos , Neoplasias , Doenças do Sistema Nervoso , Nucleotídeos , Humanos , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo , Nucleotídeos/metabolismo , Glucose/metabolismo , Animais , Transdução de Sinais
14.
J Int Med Res ; 52(5): 3000605241252115, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38713460

RESUMO

OBJECTIVE: To assess the predictive value of the serum lipid profile for initial intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: This retrospective cohort study enrolled patients with KD and divided them into IVIG-responsive and IVIG-resistant groups. They were also stratified based on the presence of CALs (CALs and non-CALs groups). Clinical, echocardiographic and biochemical values were evaluated. A subgroup analysis was performed on complete and incomplete KD. Predictors of initial IVIG resistance and CALs were determined by multivariate logistic regression analysis. RESULTS: A total of 649 KD patients were enrolled: 151 had CALs and 76 had initial IVIG resistance. Low-density lipoprotein cholesterol (LDL-C) was significantly lower in the IVIG-resistant group than in the IVIG-responsive group. LDL-C and apolipoprotein (Apo) B were significantly lower in the CALs group compared with the non-CALs group. Multivariate logistic regression failed to identify the serum lipid profile (LDL-C, Apo A or Apo B) as an independent risk factor for initial IVIG resistance or CALs in KD patients. CONCLUSION: KD patients might have dyslipidaemia in the acute phase, but the serum lipid profile might not be suitable as a single predictor for initial IVIG resistance or CALs.


Assuntos
Doença da Artéria Coronariana , Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Feminino , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/imunologia , Pré-Escolar , Estudos Retrospectivos , Lactente , LDL-Colesterol/sangue , Resistência a Medicamentos , Lipídeos/sangue , Criança , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Fatores de Risco , Apolipoproteínas B/sangue , Prognóstico
15.
J Int Med Res ; 52(5): 3000605241244743, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38713455

RESUMO

The world population is rapidly aging. Societal aging poses many challenges for individuals, families, nations, and the global healthcare system. Therefore, geriatric care is a crucial issue that demands our attention. In this case report, we describe a woman in her early 70s with multiple comorbidities, polypharmacy, and renal insufficiency who developed cefepime-induced encephalopathy with moderate to severe cerebral dysfunction during treatment of a urinary tract infection. The patient's consciousness level gradually improved, and no further seizures were observed following the discontinuation of cefepime for several days. This case report underscores the fact that polypharmacy and medication safety are significant concerns that are often overlooked when caring for older patients. The report also highlights the increased susceptibility of older individuals to antibiotic-associated adverse reactions during the management of infectious diseases. Therefore, optimization of antibiotic therapy for older patients is a critical issue that requires thorough investigation and consideration in geriatric care.


Assuntos
Antibacterianos , Encefalopatias , Cefepima , Polimedicação , Insuficiência Renal , Infecções Urinárias , Humanos , Cefepima/efeitos adversos , Cefepima/uso terapêutico , Feminino , Idoso , Encefalopatias/induzido quimicamente , Infecções Urinárias/tratamento farmacológico , Insuficiência Renal/induzido quimicamente , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico
16.
J Int Med Res ; 52(5): 3000605241248884, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38713457

RESUMO

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, benign condition affecting young Oriental-Asian females. It is characterized by fever and tender cervical lymphadenopathy with an unclear aetiology, and in most longitudinal reviews, KFD occurs before systemic lupus erythematosus (SLE). Herein, the case of a 28-year-old Kuwaiti female without any relevant past medical history, who was simultaneously diagnosed with KFD and SLE following an Ebstein-Barr virus infection, is reported. The patient was treated with oral prednisolone, hydroxychloroquine, cyclosporin, and belimumab and her response was clinically and biochemically favourable. Although KFD is prevalent in Asian populations, it may affect all races. Early diagnosis of KFD is difficult, particularly when simultaneously diagnosed with SLE, but crucial to preventing inappropriate therapy. Clinicians need to know about this rare disease, especially when patients present with fever and swollen lymph nodes, due to a risk of misdiagnosis with tuberculosis or lymphoma, as these are more often thought to be the cause of such symptoms.


Assuntos
Linfadenite Histiocítica Necrosante , Lúpus Eritematoso Sistêmico , Humanos , Linfadenite Histiocítica Necrosante/diagnóstico , Linfadenite Histiocítica Necrosante/tratamento farmacológico , Linfadenite Histiocítica Necrosante/patologia , Feminino , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Árabes , Prednisolona/uso terapêutico , Prednisolona/administração & dosagem
17.
Rev Assoc Med Bras (1992) ; 70(4): e20230871, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716932

RESUMO

OBJECTIVE: The purpose of this study was to analyze the clinical, pathological, prognostic features and treatment response of the coexistence of focal segmental glomerulosclerosis lesions with idiopathic membranous nephropathy. METHODS: This is a two-center retrospective cohort study. Patients of idiopathic membranous nephropathy were enrolled and divided into two groups with or without focal segmental glomerulosclerosis lesions according to the renal biopsy. Laboratory data and pathological manifestation were compared. Renal phospholipase A2 receptor was detected by immunofluorescence. During the follow-up, the effects of different therapies and renal function were estimated. RESULTS: A total of 236 patients were finally enrolled in this study, of which 60 and 176 idiopathic membranous nephropathy patients were enrolled in the FSGS+ and FSGS- groups, respectively. The FSGS+ group showed a higher percentage of hypertension history (38.3 vs. 20.0%, p=0.004), with a significantly higher level of systolic pressure [137 (120, 160) mmHg vs. 130 (120, 140) mmHg, p=0.009]. Main laboratory findings, including serial albumin (20.4±7.8 g/L vs. 24.5±6.7 g/L, p<0.001), 24-h proteinuria [5.61 (3.10, 7.87) g/day vs. 3.82 (2.31, 5.79) g/day, p=0.002], serial creatinine [80.8 (65.8, 97.9) µmol/L vs. 72.0 (58.7, 84.9) µmol/L, p=0.003], and estimated glomerular filtration rate [86 (66, 101) mL/min/1.73 m2 vs. 95 (81, 108) mL/min/1.73 m2, p=0.007] showed significant differences between the two groups. Pathologically, patients with focal segmental glomerulosclerosis lesions appeared with a higher percentage of crescents, a more severe degree of interstitial fibrosis, and a higher level of membranous nephropathy stage. Renal phospholipase A2 receptor showed a relatively lower positive rate of only 75.0% in the FSGS+ group in comparison with the positive rate of 90.3% in the FSGS- group (p=0.031). The prognosis was generally similar between the two groups. Among patients who were given non-immunosuppression treatment, those with focal segmental glomerulosclerosis lesions took a relatively longer period of time to achieve complete remission (29.3±7.0 m vs. 15.4±8.9 m, p=0.025) and experienced a higher rate of renal function deterioration (37.5 vs. 5.4%, p=0.033) compared with the other ones. While among those receiving immunosuppression treatment, both groups received similar remission rates. CONCLUSION: Compared with FSGS- group, idiopathic membranous nephropathy with focal segmental glomerulosclerosis lesions represented more severe nephrotic syndrome and worse renal function. In view of the renal function decline during the follow-up, more aggressive treatment with the use of immunosuppressants should be considered for idiopathic membranous nephropathy patients with focal segmental glomerulosclerosis lesions.


Assuntos
Glomerulonefrite Membranosa , Glomerulosclerose Segmentar e Focal , Imunossupressores , Humanos , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/fisiopatologia , Feminino , Masculino , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/complicações , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Imunossupressores/uso terapêutico , Biópsia , Taxa de Filtração Glomerular , Proteinúria/etiologia , Receptores da Fosfolipase A2/imunologia , Prognóstico , Resultado do Tratamento , Rim/patologia , Rim/fisiopatologia
18.
Rev Assoc Med Bras (1992) ; 70(4): e20230937, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716933

RESUMO

OBJECTIVE: Anticipatory nausea and vomiting are unpleasant symptoms observed before undergoing chemotherapy sessions. Less is known about the occurrence of symptoms since the advent of the new neurokinin-1 antagonist. METHODS: This prospective cohort study was performed at a single Brazilian Institution. This study included breast cancer patients who received doxorubicin and cyclophosphamide chemotherapy and an appropriate antiemetic regimen (dexamethasone 10 mg, palonosetron 0.56 mg, and netupitant 300 mg in the D1 followed by dexamethasone 10 mg 12/12 h in D2 and D4). Patients used a diary to record nausea, vomiting, and use of rescue medication in the first two cycles of treatment. The prevalence of anticipatory nausea and vomiting was assessed before chemotherapy on day 1 of C2. RESULTS: From August 4, 2020, to August 12, 2021, 60 patients were screened, and 52 patients were enrolled. The mean age was 50.8 (28-69) years, most had stage III (53.8%), and most received chemotherapy with curative intent (94%). During the first cycle, the frequency of overall nausea and vomiting was 67.31%, and that of severe nausea and vomiting (defined as grade>4 on a 10-point visual scale or use of rescue medication) was 55.77%. Ten patients had anticipatory nausea and vomiting (19.23%). The occurrence of nausea and vomiting during C1 was the only statistically significant predictor of anticipatory nausea and vomiting (OR=16, 95%CI 2.4-670.9, p=0.0003). CONCLUSION: The prevalence of anticipatory nausea is still high in the era of neurokinin-1 antagonists, and failure of antiemetic control in C1 remains the main risk factor. All efforts should be made to control chemotherapy-induced nausea or nausea and vomiting on C1 to avoid anticipatory nausea.


Assuntos
Antieméticos , Neoplasias da Mama , Náusea , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Antieméticos/uso terapêutico , Idoso , Náusea/induzido quimicamente , Prevalência , Brasil/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Vômito Precoce , Vômito/induzido quimicamente , Vômito/epidemiologia , Dexametasona/uso terapêutico , Palonossetrom/uso terapêutico
20.
J Cancer Res Clin Oncol ; 150(5): 244, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717526

RESUMO

PURPOSE: Cystatin SA (CST2) belongs to the superfamily of cysteine protease inhibitors. Emerging research indicates that CST2 is often dysregulated across various cancers. Its role and molecular mechanisms in gastric cancer remain underexplored. This study aims to explore the expression and function of CST2 in gastric cancer. METHODS: CST2 expression was analyzed and validated through Western blot. CST2 overexpression was induced by lentivirus in GC cells, and the correlation between CST2 expression levels and downstream signaling pathways was assessed. In addition, multiple assays, including cell proliferation, colony formation, wound-healing, and transwell migration/invasion, were considered to ascertain the influence of CST2 overexpression on gastric cancer. The cell cycle and apoptosis were detected by flow cytometry. RESULTS: CST2 expression at the protein level was decreased to be reduced in both gastric cancer tissues and cell lines, and CST2 expression attenuate gastric cancer growth, an effect restricted to gastric cancer cells and absent in gastric epithelial GES-1 cells. Furthermore, CST2 was demonstrated to improve chemosensitivity to Oxaliplatin in gastric cancer cells through the PI3K/AKT signaling pathway. CONCLUSION: These findings indicate that CST2 is downregulated at the protein level in gastric cancer tissues and cell lines. Additionally, CST2 was found to attenuate the growth of gastric cancer cells and to enhance sensitivity to Oxaliplatin through the PI3K/AKT signaling pathway, specific to gastric cancer cell lines. CST2 may serve as a tumor suppressor gene increasing sensitivity to Oxaliplatin in gastric cancer.


Assuntos
Proliferação de Células , Oxaliplatina , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Humanos , Oxaliplatina/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Cistatinas Salivares/metabolismo , Cistatinas Salivares/genética , Apoptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Movimento Celular/efeitos dos fármacos
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