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This study explore the molecular mechanism of the synergistic effect of Chinese Yam polysaccharides and nucleoside analogues(NAs) on hepatitis B virus(HBV) resistance. Different concentrations of Chinese Yam polysaccharide and entecavir were ad-ded to HepG2.2.15 cells. After the cytotoxicity was detected by cell counting kit-8(CCK-8), the optimal concentration and time of the two drugs to inhibit HepG2.2.15 cells were screened out. They were divided into control group, Chinese Yam polysaccharide group, entecavir group and combination drug group(Chinese Yam polysaccharide + entecavir). The drugs were added to HepG2.2.15 cells, ELISA was used to detect the effects of each group of drugs on the secretion of hepatitis B virus surface antigen(HBsAg) and hepatitis B virus e antigen(HBeAg) in cell supernatant, probe quantitative real-time PCR(probe qRT-PCR) was used to detect the effects of drugs on HBV-DNA in HepG2.2.15 cells, and Western blot was used to detect the effects of each group of drugs on the expression of p38 MAPK, p-p38 MAPK, NTCP proteins in HepG2.2.15 cells. The qRT-PCR was used to detect the effect of drugs on the expression of p38 MAPK and NTCP mRNA in HepG2.2.15 cells. The results showed that compared with control group, the concentrations of HBeAg and HBsAg in Chinese Yam polysaccharide group, entecavir group and combination group decreased(P<0.01 or P<0.001), and both of them inhibited HBV-DNA in HepG2.2.15 cells(P<0.01), and the HBV-DNA inhibition of HepG2.2.15 cells in the combination group was more obvious(P<0.001), and the protein expression levels of p-p38 MAPK and NTCP were significantly decreased(P<0.05 or P<0.01), the mRNA expression level of p38 MAPK increased, and the mRNA expression level of NTCP decreased(P<0.05 or P<0.01). To sum up, Chinese Yam polysaccharide can reduce the expression of NTCP protein and mRNA through p38 MAPK signaling pathway and cooperate with entecavir in anti-HBV.
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Antivirales , Dioscorea , Virus de la Hepatitis B , Polisacáridos , Proteínas Quinasas p38 Activadas por Mitógenos , Humanos , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Polisacáridos/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Células Hep G2 , Antivirales/farmacología , Dioscorea/química , Sinergismo Farmacológico , Nucleósidos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Antígenos de Superficie de la Hepatitis B/metabolismo , Antígenos de Superficie de la Hepatitis B/genética , Antígenos e de la Hepatitis B/metabolismo , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Guanina/análogos & derivados , Guanina/farmacologíaRESUMEN
BACKGROUND: Pulmonary mucoepidermoid carcinoma (PMEC) is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree. The clear cell variant of PMEC is exceptionally uncommon and presents notable diagnostic challenges, primarily attributable to its morphological similarity to other tumors containing clear cells. CASE SUMMARY: A 22-year-old male, formerly in good health, came in with a two-month duration of persistent cough and production of sputum. Subsequent imaging and bronchoscopy examinations revealed a 2 cm tumor in the distal left main bronchus, which resulted in complete atelectasis of the left lung. Further assessment via positron emission tomography/computed tomography scans and endoscopic biopsy confirmed the primary malignant nature of the tumor, characterized by clear cell morphology in most of the tumor cells. The patient underwent a left lower lobe sleeve resection accompanied by systematic mediastinal lymph node dissection. Molecular pathology analysis subsequently revealed a CRTC3-MAML2 gene fusion, leading to a definitive pathological diagnosis of the clear cell variant of PMEC, staged as T2N0M0. After surgery, the patient experienced a smooth recovery and exhibited no signs of recurrence during the one-and-a-half-year follow-up period. CONCLUSION: This article describes an unusual case of a clear cell variant of PMEC characterized by the presence of a CRTC3-MAML2 gene fusion in a 22-year-old male. The patient underwent successful left lower lobe sleeve resection. This case underscores the distinctive challenges associated with diagnosing and treating this uncommon malignancy, underscoring the importance of precise diagnosis and personalized treatment strategies.
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Esophagogastric variceal bleeding (EVB) is one of the common digestive system emergencies with poor prognosis and high rate of rebleeding after treatment. To explore the effects of endoscopic therapy and drug therapy on the prognosis and rebleeding of patients with EVB, and then select better treatment methods to effectively improve the prognosis. From January 2013 to December 2022, 965 patients with EVB who were hospitalized in gastroenterology Department of the 940 Hospital of Joint Logistic Support Forces of PLA were retrospectively analyzed. Patients were divided into endoscopic treatment group (ET, n = 586) and drug treatment group (DT, n = 379). Propensity score matching (PSM) analysis was performed in both groups, and the general information, efficacy and length of hospital stay were recorded. The patients were followed up for 3 months after bleeding control to determine whether rebleeding occurred. There were 286 cases in each group after PSM. Compared with DT group, ET had higher treatment success rate (P < 0.001), lower rebleeding rate (P < 0.001), lower mortality rate within 3 months, and no significant difference in total hospital stay (P > 0.05). Compared with drug therapy, endoscopic treatment of EVB has short-term efficacy advantages, and can effectively reduce the incidence of rebleeding and mortality within 3 months.
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Várices Esofágicas y Gástricas , Humanos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/terapia , Estudios Retrospectivos , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Endoscopía/efectos adversos , Pronóstico , Resultado del Tratamiento , RecurrenciaRESUMEN
Opioids are widely used in the treatment of moderate and severe pain. Nociceptive stimulation has been reported to potentially promote microglial activation and neuroinflammation, which also causes chronic pain sensitization. The aim of this study was to demonstrate whether the novel µ receptor agonist MEL-0614 could inhibit activated microglia directly and the associated signaling pathway. Mice were administered lipopolysaccharide and formalin to induce allodynia. Von Frey test was used to detect the anti-allodynia effect of MEL-0614 before and after LPS and formalin injection. In the spinal cord, the levels of proinflammatory cytokines and microglial activation were determined after MEL-0614 administration. BV2 and primary microglia were cultured to further explore the effect of MEL-0614 on LPS-induced microglial activation and key signaling pathways involved. MEL-0614 partially prevented and reversed allodynia induced by LPS and formalin in vivo, which was not inhibited by the µ receptor antagonist CTAP. Minocycline was effective in reversing the established allodynia. MEL-0614 also downregulated the activation of microglia and related proinflammatory cytokines in the spinal cord. Additionally, in BV2 and primary microglia, MEL-0614 inhibited the LPS-induced upregulation of proinflammatory factors, which was unaffected by CTAP. The NLR family pyrin domain containing 3 (NLRP3) related signaling pathway may be involved in the interaction between MEL-0614 and microglia. The opioid agonist MEL-0614 inhibited the activation of microglia and the subsequent upregulation of proinflammatory factors both in vivo and in vitro. Notably, this effect is partially mediated by the µ receptor.
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Hiperalgesia , Microglía , Ratones , Animales , Hiperalgesia/metabolismo , Receptores Opioides mu/metabolismo , Lipopolisacáridos/farmacología , Dolor/inducido químicamente , Citocinas/metabolismo , Formaldehído/efectos adversosRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) was first detected in December 2019, and declared as a pandemic by the World Health Organization (WHO) on March 11, 2020. The current management of COVID-19 is based generally on supportive therapy and treatment to prevent respiratory failure. METHODS: PubMed, Web of Science, Embase, CNKI, and other databases were searched by computer, and relevant literature published from December 2019 to November 2022 on the influencing factors of infection in close contacts with novel coronavirus pneumonia was collected. Meta-analysis was carried out after literature screening, quality assessment, and data extraction. RESULTS: A total of 425 articles were retrieved and 11 were included. Meta-analysis showed that there were 6 risk factors, and the combined OR value and 95% CI of each influencing factor were 5.23 (3.20, 8.57) for family members, 1.63 (0.56, 4.77) for regular contact, 2.14 (0.62, 7.32) for the elderly, 0.58 (0.001569.89) for cohabitation, 1.97 (1.02, 3.82) for women and 0.75 (0.01, 54.07) for others. The Deeks' funnel diagram indicates that there is no potential publication bias among the included studies. CONCLUSION: Family members and gender differences are the risk factors of infection among close contacts, and it cannot be proved that there are differences in infection among frequent contact, advanced age, and living together.
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COVID-19 , Femenino , Humanos , Anciano , COVID-19/epidemiología , SARS-CoV-2 , Pandemias/prevención & control , Factores de RiesgoRESUMEN
This study explored the molecular mechanism of acteoside against hepatoma 22(H22) tumor in mice through c-Jun N-terminal kinase(JNK) signaling pathway. H22 cells were subcutaneously inoculated in 50 male BALB/c mice, and then the model mice were classified into model group, low-dose, medium-dose, and high-dose acteoside groups, and cisplatin group. The administration lasted 2 weeks for each group(5 consecutive days/week). The general conditions of mice in each group, such as mental status, diet intake, water intake, activity, and fur were observed. The body weight, tumor volume, tumor weight, and tumor-inhibiting rate were compared before and after administration. Morphological changes of liver cancer tissues were observed based on hematoxylin and eosin(HE) staining, and the expression of phosphorylated(p)-JNK, JNK, B-cell lymphoma-2(Bcl-2), Beclin-1, and light chain 3(LC3) in each tissue was detected by immunohistochemistry and Western blot. qRT-PCR was performed to detect the mRNA expression of JNK, Bcl-2, Beclin-1, and LC3. The general conditions of mice in model and low-dose acteoside groups were poor, while the general conditions of mice in the remaining three groups were improved. The body weight of mice in medium-dose acteoside group, high-dose acteoside group, and cisplatin group was smaller than that in model group(P<0.01). The tumor volume in model group was insignificantly different from that in low-dose acteoside group, and the volume in cisplatin group showed no significant difference from that in high-dose acteoside group. Tumor volume and weight in medium-dose and high-dose acteoside groups and cisplatin group were lower than those in the model group(P<0.001). The tumor-inhibiting rates were 10.72%, 40.32%, 53.79%, and 56.44% in the low-dose, medium-dose, and high-dose acteoside groups and cisplatin group, respectively. HE staining showed gradual decrease in the count of hepatoma cells and increasing sign of cell necrosis in the acteoside and cisplatin groups, and the necrosis was particularly obvious in the high-dose acteoside group and cisplatin group. Immunohistochemical results suggested that the expression of Beclin-1, LC3, p-JNK, and JNK was up-regulated in acteoside and cisplatin groups(P<0.05). The results of immunohistochemistry, Western blot, and qRT-PCR indicated that the expression of Bcl-2 was down-regulated in the medium-dose and high-dose acteoside groups and cisplatin group(P<0.01). Western blot showed that the expression of Beclin-1, LC3, and p-JNK was up-regulated in acteoside and cisplatin groups(P<0.01), and there was no difference in the expression of JNK among groups. qRT-PCR results showed that the levels of Beclin-1 and LC3 mRNA were up-regulated in the acteoside and cisplatin groups(P<0.05), and the level of JNK mRNA was up-regulated in medium-dose and high-dose acteoside groups and cisplatin group(P<0.001). Acteoside promotes apoptosis and autophagy of H22 cells in mice hepatoma cells by up-regulating the JNK signaling pathway, thus inhibiting tumor growth.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Animales , Ratones , Cisplatino/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Sistema de Señalización de MAP Quinasas , Beclina-1 , Apoptosis , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Necrosis , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Línea Celular Tumoral , ARN Mensajero/metabolismo , AutofagiaRESUMEN
BACKGROUND: Pulmonary mucormycosis is a rare but life-threatening invasive fungal infection that mostly affects immunocompromised patients. This disease usually develops acutely and progresses rapidly, often leading to a poor clinical prognosis. Chronic pulmonary mucormycosis is highly unusual in immunocompetent patients. CASE SUMMARY: A 43-year-old man, who was a house improvement worker with a long history of occupational dust exposure, presented with an irritating cough that had lasted for two months. The patient was previously in good health, without dysglycemia or any known immunodeficiencies. Chest computed tomography revealed a mass in the left lower lobe, measuring approximately 6 cm in diameter, which was suspected to be primary lung carcinoma complicated with obstructive pneumonia. Thoracoscopic-assisted left lower lobectomy was performed, and metagenomic next-generation sequencing detection, along with special pathological staining of surgical specimens, suggested Rhizopus microsporus infection. Postoperatively, the patient's respiratory symptoms were relieved, and no signs of recurrence were found during the six-month follow-up. CONCLUSION: This article reports a rare case of chronic pulmonary mucormycosis caused by Rhizopus microsporus in a middle-aged male without dysglycemia or immunodeficiency. The patient's surgical outcome was excellent, reaffirming that surgery remains the cornerstone of pulmonary mucormycosis treatment.
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Retiform hemangioendothelioma (RH) is a type of low-grade malignant angiosarcoma. It commonly involves the skin and subcutaneous tissue of the lower extremities, but a few cases have been reported in the gut. However, hepatic RH has not been previously reported. This report presents the case of RH of the liver in a 61-year-old woman who was admitted to the hospital having presented with liver space-occupying lesions of 2 months evolution. The patient underwent an abdominal ultrasound examination, which indicated a hemangioma, but abdominal computed tomography diagnosed a liver abscess. In order to determine the nature of the lesion, an ultrasound-guided liver biopsy was performed, after which a pathological diagnosis confirmed the presence of RH in the liver. The patient underwent ultrasound-guided microwave ablation three times and has been followed up for 8 years with no tumor recurrence or metastasis. Surgical excision is still the first choice for the treatment of hepatic RH. As shown in this case, however, for patients who refuse to undergo surgery or have surgical contraindications, ultrasound-guided microwave ablation is an alternative treatment option. The report of this case expands the scope of liver tumors to a certain extent and provides a reference for clinical diagnosis and treatment.
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Objective: To detect expression and phosphorylation level of macrophage migration inhibitor (MIF) and extracellular-regulated kinases 1 and 2 (ERK1/2) in hepatitis B-induced liver cirrhosis (HBILC) and hepatocellular carcinoma (HCC) with a background of HBILC and analyze the correlation of MIF and ERK1/2 with HBILC and HCC. Methods: Twenty cases of normal liver tissues were collected as a control group, and 48 specimens of HBILC tissues and 48 specimens of HCC tissues were collected as the experimental group, which were assigned as the HBILC group and HCC group, respectively. All tissue specimens were processed into tissue chips. The expressions of MIF, ERK1/2, and their phosphorylated proteins were detected via immunohistochemistry, and MIF and ERK1/2 nucleic acid expressions were detected by in situ hybridization. The results were statistically analyzed using the chi-square test. Results: Proteins and nucleic acids of MIF and ERK1/2 presented low expression in the control group and high expression in the HBILC group and HCC group. MIF expression in the three groups was 25.0%, 75.0%, and 79.17%, respectively, while that of the nucleic acids was 25.0%, 70.83%, and 68.75%, respectively. Expression of ERK1/2 in the three groups was 40.0%, 60.42%, and 81.25%, respectively, and that of nucleic acids was 40.0%, 79.17%, and 77.08%. Expression of pERK1/2 was low in the control and HBILC group and high in the HCC group. Expression of pERK1/2 in the three groups was 20%, 45.83%, and 75%, respectively. Expression of pERK1/2 in the HCC group was significantly different from that in the HBILC and control group (P<0.05), but the difference between the HBILC group and control group was not statistically significant (P>0.05). Conclusion: Occurrence and development of HBILC and HCC are not only related to the high expression of MIF but also closely related to the activation of the ERK1/2 signaling pathway.
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INTRODUCTION: Necrotizing fasciitis (NF) is a rare, severe soft tissue infection, characterized by rapid and extensive necrosis of the skin, subcutaneous tissue, and superficial and deep fascia. It is frequently misdiagnosed as other infectious diseases, leading to inappropriate treatment and potentially serious consequences. It may be complicated by septic shock and multiple organ failure with a fatal outcome. PATIENT CONCERNS: A 73-year-old woman presented with continuous itching, skin lesions, pain, and swelling of the outer side of her left leg. The patient was diagnosed with septic shock and multiorgan failure caused by left leg NF. DIAGNOSIS: Septic shock and multiorgan failure caused by left leg NF. INTERVENTIONS: Two surgeries were performed on the patient's leg, which effectively treated her septic shock and multiple organ dysfunction. OUTCOMES: The patient was followed up three times after her discharge. She had a good recovery, was generally well with no significant sequelae, and returned to her regular life. CONCLUSION: NF is an acute severe illness with high mortality. It is easily misdiagnosed, leading to delayed or erroneous treatment and serious (or potentially fatal) outcomes. Rapid and accurate diagnosis of NF is essential for patient recovery. In difficult cases, multidisciplinary consultations may be helpful. The management of NF includes early and thorough surgical debridement, antibiotics, and symptomatic treatment.
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Fascitis Necrotizante , Choque Séptico , Humanos , Femenino , Anciano , Fascitis Necrotizante/diagnóstico , Fascitis Necrotizante/cirugía , Choque Séptico/etiología , Pierna , Diagnóstico Tardío/efectos adversos , Antibacterianos/uso terapéuticoRESUMEN
Despite the rapid deployment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, the emergence of SARS-CoV-2 variants and reports of their immune evasion characteristics have led to an urgent need for novel vaccines that confer potent cross-protective immunity. In this study, we constructed three different SARS-CoV-2 spike S1-conjugated nanoparticle vaccine candidates that exhibited high structural homogeneity and stability. Notably, these vaccines elicited up to 50-times-higher neutralizing antibody titers than the S1 monomer in mice. Crucially, it was found that the S1-conjugated nanoparticle vaccine could elicit comparable levels of neutralizing antibodies against wild-type or emerging variant SARS-CoV-2, with cross-reactivity to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), the effect of which could be further enhanced using our designed nanoparticles. Our results indicate that the S1-conjugated nanoparticles are promising vaccine candidates with the potential to elicit potent and cross-reactive immunity against not only wild-type SARS-CoV-2, but also its variants of concern, variants of interest, and even other pathogenic betacoronaviruses. IMPORTANCE The emergence of SARS-CoV-2 variants led to an urgent demand for a broadly effective vaccine against the threat of variant infection. The spike protein S1-based nanoparticle designed in our study could elicit a comprehensive humoral response toward different SARS-CoV-2 variants of concern and variants of interest and will be helpful to combat COVID-19 globally.
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Formación de Anticuerpos , Vacunas contra la COVID-19 , COVID-19 , Nanopartículas , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Formación de Anticuerpos/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Humanos , Ratones , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
BACKGROUND: Eosinophilic gastroenteritis is a rare gastrointestinal disease that is characterized by diffuse or localized eosinophil infiltration in the gastrointestinal tract, and is accompanied by increased peripheral blood eosinophils. Herein, a case of plasma membrane lesion-type total intestinal eosinophil enteritis is reported. CASE PRESENTATION: We report on a 20-year-old male patient who was admitted to the hospital with "abdominal distension for 15 days". The infiltration of a large number of eosinophils was found by conducting an intestinal biopsy, routine ascites examination, blood routine, smear test, and a bone marrow puncture. A special feature of this patient was that a large number of eosinophils were found in the duodenum, small intestine, and colon. The final diagnosis was plasma membrane lesion type total intestinal eosinophilic enteritis. After four weeks of prednisone treatment, the symptoms disappeared completely and the entire intestinal mucosa was endoscopically observed as smooth. CONCLUSION: Clinical practitioners must pay attention to gastrointestinal endoscopy and biopsy pathology results for patients presenting with abdominal distention and ascites. Combined with an abnormal increase of eosinophils in ascites, bone marrow, and peripheral blood, clinical practitioners must be highly vigilant against plasma membrane lesion type total intestinal eosinophilic enteritis.
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Enteritis , Eosinofilia , Adulto , Ascitis/complicaciones , Membrana Celular/patología , Enteritis/complicaciones , Enteritis/diagnóstico , Enteritis/tratamiento farmacológico , Eosinofilia/complicaciones , Eosinofilia/patología , Gastritis , Humanos , Masculino , Adulto JovenRESUMEN
AIM: To explore the regulatory mechanism of nuclear paraspeckle assembly transcript 1 (NEAT1) in the pathogenesis of posterior capsule opacification (PCO). METHODS: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was executed to analyze NEAT1 and microRNA (miR)-26a-5p expression in transforming growth factor-beta 2 (TGF-ß2)-disposed lens epithelial cells (LECs). The proliferation, cell cycle progression, apoptosis, and migration of TGF-ß2-disposed LECs were evaluated. The relationship between NEAT1 or fanconi anemia (FA) complementation group E (FANCE) and miR-26a-5p was verified by dual-luciferase reporter assay. RESULTS: TGF-ß2 induced NEAT1 expression in LECs. NEAT1 inhibition accelerated apoptosis, cell cycle arrest, decreased proliferation, epithelial-mesenchymal transition (EMT), and migration of TGF-ß2-disposed LECs. NEAT1 sponged miR-26a-5p to further regulate FANCE expression. Rescue experiments presented that miR-26a-5p downregulation overturned NEAT1 silencing-mediated impacts on TGF-ß2-disposed LEC biological behaviors. Additionally, FANCE overexpression reversed miR-26a-5p mimic-mediated impacts on TGF-ß2-disposed LEC biological behaviors. CONCLUSION: TGF-ß2-induced NEAT1 facilitates LEC proliferation, migration, and EMT by upregulating FANCE via sequestering miR-26a-5p.
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Anemia , Anemia/epidemiología , Anemia/etiología , Beijing/epidemiología , Niño , Estudios Transversales , Humanos , Estado Nutricional , PrevalenciaRESUMEN
Epstein-Barr virus (EBV) infection is a global health concern infecting over 90% of the population. However, there is no currently available vaccine. EBV primarily infects B cells, where the major glycoprotein 350 (gp350) is the main target of neutralizing antibodies. Given the advancement of nanoparticle vaccines, we describe rationally designed vaccine modalities presenting 60 copies of gp350 on self-assembled nanoparticles in a repetitive array. In a mouse model, gp350s on lumazine synthase (LS) and I3-01 adjuvanted with MF59 or aluminum hydroxide (Alhydrogel) elicited over 65- to 133-fold higher neutralizing antibody titers than the corresponding gp350 monomer to EBV. Furthermore, immunization with gp350D123-LS and gp350D123-I3-01 vaccine induced a Th2-biased response. For the nonhuman primate model, gp350D123-LS in MF59 elicited higher titers of total IgG and neutralizing antibodies than the monomeric gp350D123. Overall, these results support gp350D123-based nanoparticle vaccine design as a promising vaccine candidate for potent protection against EBV infection.
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Infecciones por Virus de Epstein-Barr , Nanopartículas , Vacunas , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infecciones por Virus de Epstein-Barr/prevención & control , Herpesvirus Humano 4 , Inmunización , RatonesRESUMEN
BACKGROUND: Avian paramyxoviruses (APMVs), also termed avian avulaviruses, are of a vast diversity and great significance in poultry. Detection of all known APMVs is challenging, and distribution of APMVs have not been well investigated. METHODS: A set of reverse transcription polymerase chain reaction (RT-PCR) assays for detection of all known APMVs were established using degenerate primers targeting the viral polymerase L gene. The assays were preliminarily evaluated using in-vitro transcribed double-stranded RNA controls and 24 known viruses, and then they were employed to detect 4,346 avian samples collected from 11 provinces. RESULTS: The assays could detect 20-200 copies of the double-stranded RNA controls, and detected correctly the 24 known viruses. Of the 4,346 avian samples detected using the assays, 72 samples were found positive. Of the 72 positives, 70 were confirmed through sequencing, indicating the assays were specific for APMVs. The 4,346 samples were also detected using a reported RT-PCR assay, and the results showed this RT-PCR assay was less sensitive than the assays reported here. Of the 70 confirmed positives, 40 were class I Newcastle disease virus (NDV or APMV-1) and 27 were class II NDV from poultry including chickens, ducks, geese, and pigeons, and three were APMV-2 from parrots. The surveillance identified APMV-2 in parrots for the first time, and revealed that prevalence of NDVs in live poultry markets was higher than that in poultry farms. The surveillance also suggested that class I NDVs in chickens could be as prevalent as in ducks, and class II NDVs in ducks could be more prevalent than in chickens, and class II NDVs could be more prevalent than class I NDVs in ducks. Altogether, we developed a set of specific and sensitive RT-PCR assays for detection of all known APMVs, and conducted a large-scale surveillance using the assays which shed novel insights into APMV epidemiology.
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The coronavirus disease pandemic of 2019 (COVID-19) caused by the novel SARS-CoV-2 coronavirus resulted in economic losses and threatened human health worldwide. The pandemic highlights an urgent need for a stable, easily produced, and effective vaccine. SARS-CoV-2 uses the spike protein receptor-binding domain (RBD) to bind its cognate receptor, angiotensin-converting enzyme 2 (ACE2), and initiate membrane fusion. Thus, the RBD is an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticle vaccine candidates, namely, RBD-Ferritin (24-mer), RBD-mi3 (60-mer), and RBD-I53-50 (120-mer), via covalent conjugation using the SpyTag-SpyCatcher system. When mice were immunized with the RBD-conjugated nanoparticles (NPs) in conjunction with the AddaVax or Sigma Adjuvant System, the resulting antisera exhibited 8- to 120-fold greater neutralizing activity against both a pseudovirus and the authentic virus than those of mice immunized with monomeric RBD. Most importantly, sera from mice immunized with RBD-conjugated NPs more efficiently blocked the binding of RBD to ACE2 in vitro, further corroborating the promising immunization effect. Additionally, the vaccine has distinct advantages in terms of a relatively simple scale-up and flexible assembly. These results illustrate that the SARS-CoV-2 RBD-conjugated nanoparticles developed in this study are a competitive vaccine candidate and that the carrier nanoparticles could be adopted as a universal platform for a future vaccine development.
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Enzima Convertidora de Angiotensina 2/metabolismo , Vacunas contra la COVID-19/uso terapéutico , COVID-19/prevención & control , Nanopartículas/uso terapéutico , SARS-CoV-2/fisiología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Animales , COVID-19/metabolismo , Vacunas contra la COVID-19/farmacología , Chlorocebus aethiops , Femenino , Células HEK293 , Interacciones Huésped-Patógeno , Humanos , Ratones , Ratones Endogámicos BALB C , Modelos Moleculares , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Glicoproteína de la Espiga del Coronavirus/química , Células VeroRESUMEN
BACKGROUND: COVID-19 is novel infectious disease with an evolving understanding of its epidemiology and clinical manifestations. Severe cases developed life-threatening complications, such as respiratory failure, shock, and multiple organs dysfunction. Immunocompromised patients often present atypical presentations of viral infected diseases. CASE PRESENTATION: We report newly diagnosed HIV infections in two patients with COVID-19 in China. In our two cases, both patients with elevated IL-6 received Tocilizumab treatment, but did not present obvious therapeutic effect. CONCLUSIONS: These cases highlight possible co-detection of known immunocompromised diseases such as HIV. The two cases we reported stressed the risk of misdiagnosis, especially during the pandemic of an infectious disease and the importance of extended testing even if in immune-compromised condition the immune state may be ignored.
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Infecciones por Coronavirus/complicaciones , Infecciones por VIH/complicaciones , Neumonía Viral/complicaciones , Adulto , Betacoronavirus , COVID-19 , China , Infecciones por Coronavirus/inmunología , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Humanos , Huésped Inmunocomprometido , Masculino , Pandemias , Neumonía Viral/inmunología , SARS-CoV-2RESUMEN
This study aimed to explore the influence of Tryptophanyl-tRNA synthetase (WARS) expression on the proliferation and migration of uveal melanoma (UM) cells, and the potential mechanisms. Bioinformatics analysis based on Gene Expression Omnibus (GEO) database showed that WARS expression in metastatic cancer was significantly higher than that in no-metastatic group. Kaplan-Meier analysis based on The Cancer Genome Atlas (TCGA) database showed that high WARS expression was associated with lower survival. Biological function experiments showed that overexpression of WARS in OCM-1A cells can promote cell proliferation, migration, and invasion, whereas knockdown of WARS in C918 cells showed the opposite effect. Finally, we observed that the up-regulation of WARS induced the activation of phosphatidylinositol 3-kinase/AKT (PI3K/AKT) signaling, whilst depletion of WARS resulted in opponent outcomes. Taken together, our results illustrated that WARS was overexpressed in UM cells and contributed to the viability and motility of UM cells via modulating PI3K/AKT signaling pathway.