RESUMO
This paper describes emergent stigma-related themes from individual descriptions of living with HIV in Liuzhou, China. Qualitative interviews were conducted with 23 people living with HIV (PLHIV). To provide contextual information, 14 public health personnel and 4 community workers in Liuzhou were also interviewed. PLHIV experienced enacted, anticipated, and internalized HIV-related stigma, which resulted in negative affective, behavioral, and physical health outcomes, including barriers to health care, preemptive self-isolation, suicidal ideation, and poverty. To lessen stigma, future programs should aim to increase HIV knowledge and empathy for PLHIV among family members, community workers, and health professionals. HIV programs should also include suicide risk assessment for PLHIV, especially immediately after diagnosis and at the onset of HIV-related symptoms.
Assuntos
Infecções por HIV/psicologia , Pessoal de Saúde/psicologia , Discriminação Social , Estigma Social , Atitude do Pessoal de Saúde , China , Família , Feminino , Grupos Focais , Humanos , Relações Interpessoais , Entrevistas como Assunto , Masculino , Pesquisa Qualitativa , Isolamento Social , Fatores SocioeconômicosRESUMO
Hepatocellular carcinoma (HCC) is the most common form of liver cancer with poor prognosis. The available drugs for advanced HCC are limited and substantial therapeutic advances including new drugs and new combination therapies are still in urgent need. In this study, we found that the major metabolite of Lactobacillus reuteri (L. reuteri), reuterin showed great anti-HCC potential and could help in sorafenib treatment. Reuterin treatment impaired mitophagy and caused the aberrant clustering of mitochondrial nucleoids to block mitochondrial DNA (mtDNA) replication and mitochondrial fission, which could promote mtDNA leakage and subsequent STING activation in HCC cells. STING could activate pyroptosis and necroptosis, while reuterin treatment also induced caspase 8 expression to inhibit necroptosis through cleaving RIPK3 in HCC cells. Thus, pyroptosis was the main death form in reuterin-treated HCC cells and STING suppression remarkably rescued the growth inhibitory effect of reuterin and concurrently knockdown caspase 8 synergized to restrain the induction of pyroptosis. In conclusion, our study explains the detailed molecular mechanisms of the antitumor effect of reuterin and reveals its potential to perform as a combinational drug for HCC treatment.
Assuntos
Carcinoma Hepatocelular , Caspase 8 , DNA Mitocondrial , Neoplasias Hepáticas , Proteínas de Membrana , Piroptose , Humanos , Piroptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Caspase 8/metabolismo , Caspase 8/genética , DNA Mitocondrial/genética , Linhagem Celular Tumoral , Animais , Camundongos , Sorafenibe/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Hepatocellular carcinoma is one of the most common fatal malignancies worldwide. Thus far, the hepatocellular carcinoma prognosis has been bleak due to deficiencies in the identification and diagnosis of early hepatocellular carcinoma. Ciclopirox olamine (CPX) is a synthetic antifungal agent and has been considered as an anti-cancer candidate drug recently, though the detailed mechanisms related to its anti-cancer effect in hepatocellular carcinoma have not yet been revealed. Here, we found that CPX could inhibit proliferation in HCC cells but not in intrahepatic cholangiocarcinoma cells by arresting the cell cycle. Moreover, the anti-cancer effects of CPX in HCC cells were also attributed to CPX-triggered ROS accumulation and DJ-1 downregulation. Additionally, CPX could promote complete autophagic flux, which alleviated the anti-cancer effect of CPX in HCC cells, whereas the ROS scavenger (NAC) would attenuate CPX-induced protective autophagy. Interestingly, CPX could also induce glycogen clustering in HCC cells. Altogether, this study provides a new insight into the detailed molecular mechanisms of CPX as an anti-cancer therapy and a strategy for treating hepatocellular carcinoma.
RESUMO
Cervical cancer is one of the most common gynecological malignancies with poor prognosis due to constant chemoresistance and repeated relapse. Ciclopirox olamine (CPX), a synthetic antifungal agent, has recently been identified to be a promising anti-cancer candidate. However, the detailed mechanisms related to its anti-cancer effects remain unclear and need to be further elucidated. In this study, we found that CPX could induce proliferation inhibition in cervical cancer cells by targeting PARK7. Further results demonstrated that CPX could induce cytoprotective autophagy by downregulating the expression of PARK7 to activate PRKAA1 or by PARK7-independent accumulation of ROS to inhibit mTOR signaling. Meanwhile, CPX treatment increased the glycogen clustering and glycophagy in cervical cancer cells. The presence of N-acetyl-l-cysteine (NAC), a ROS scavenger, led to further clustering of glycogen in cells by reducing autophagy and enhancing glycophagy, which promoted CPX-induced inhibition of cervical cancer cell proliferation. Together, our study provides new insights into the molecular mechanisms of CPX in the anti-cancer therapy and opens new avenues for the glycophagy in cancer therapeutics.
Assuntos
Neoplasias do Colo do Útero , Apoptose , Autofagia , Ciclopirox/farmacologia , Feminino , Glicogênio/farmacologia , Humanos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologiaRESUMO
A novel magnetic heavy metal adsorbent was prepared via diethylenetriamine (DETA) modification on magnetic hydrothermal carbon, with glucose and sugar-containing waste water as the carbon source. The prepared materials were characterized by FT-IR, SEM, TEM, EDXRF, TGA, elemental analysis, XPS, and magnetic moment determination. In this paper, the adsorption mechanism of the modified and unmodified adsorbents was well discussed. Four kinds of waste water (watermelon juice, expired sprite, sugar-pressing waste water, and confectionary waste water) were employed to produce heavy metal ion adsorbents; the chemical properties of hydrothermal carbon derived from the proposed sources were analyzed as well. The maximum uptake capacity for Cu2+, Pb2+, and Cd2+ of the adsorbent produced from glucose was 26.88, 103.09, and 25.38 mg g-1, respectively. After 5 cycles, the adsorption ability was still well preserved. This work represents an efficient new direction for the treatment of heavy metal ions in water and the reuse of sugar-containing waste water. Graphical abstract The schemetic of DETA-modified magnetic carbon preparing from sugar-containing wastewater.