Emetine, an isoquinoline alkaloid that is enriched at high concentrations in the lung, has shown potent in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to better understand the effectiveness of low-dose emetine for patients with coronavirus disease 2019 (COVID-19).In this real-world study, 63 patients with mild or common COVID-19 were recruited from Wuhan Fangcang Shelter Hospital and five COVID-19-designated hospitals in Anhui Province, China from February to March 2020. Thirty-nine patients from Wuhan Fangcang Shelter Hospital were assigned to a pragmatic randomized controlled clinical trial, and 24 patients from the 5 COVID-19-designated hospitals in Anhui Province underwent a real-world study. The medication course of emetine was less than 10 days. The main symptoms and adverse reactions of all patients were observed and recorded. The primary outcome measure was the time required for a negative SARS-CoV-2 RNA result or the negative result rate on day 10. Secondary outcomes included axillary temperature, transcutaneous oxygen saturation, and respiratory frequency recovery. The study was approved by the Ethics Committee of The First Affiliated Hospital of Anhui Medical University on February 20, 2019 (approval No. PJ2020-03-19) and was registered with the Chinese Clinical Trial Registry on February 20, 2019 (registration number: ChiCTR2000030022).The oxygen saturation values were higher in the treatment group than in the control group on the first day after enrollment for patients treated at Fangcang Shelter Hospital. The axillary body temperature, respiratory rate, and oxygen saturation among patients in Fangcang Shelter Hospital were related to the time effect but not to the intervention measures. The respiratory rate and oxygen saturation of patients in the Anhui designated hospitals were related to the intervention measures but not to the time effect. The axillary body temperature of patients in Anhui designated hospitals was related to the time effect but not to the intervention measures.Our preliminary study shows that low-dose emetine combined with basic conventional antiviral drugs improves clinical symptoms in patients with mild and common COVID-19 without apparent adverse effects, suggesting that moderately increased doses of emetine may have good potential for treatment and prevention of COVID-19.
The global pandemic of COVID-19 has attracted extensive drug searching interets for the new coronavirus SARS-CoV-2. Although currently several of clinically used "old" drugs have been repurposed to this new disease for the urgent clinical investigation, there is still great demand for more effective therapies for the anti-infections. Here we report the discovery that an "old" drug Emetine could potently inhibit SARS-CoV-2 virus replication and displayed virus entry blocking effect in Vero cells at low dose. In addition, Emetine could significantly reduce the lipopolysaccharide (LPS) induced interleukin-6 (IL-6) protein level and moderately reduce the tumor necrosis factor (TNF-α) protein level in the M1 polarized THP-1 macrophages. In vivo animal pharmacokinetics (PK) study revealed that Emetine was enriched in the lung tissue and had a long retention time (over 12 h). With 1 mg/kg single oral dose, the effective concentration of Emetine in lung was up to 1.8 μM (mice) and 1.6 μM (rats) at 12 h, which is over 200-fold higher than the EC50 of the drug. The potent in vitro antiviral replication efficacy and the high enrichment in target tissue, combining with the well documented safety profiles in human indicate that low dose of Emetine might be a potentially effective anti-SARS-CoV-2 infection therapy.
To study and analyze the diagnostic value and interventional treatment value of high-frequency ultrasound for elbow cyst.From February 2018 to February 2021, the data of 60 patients with elbow cyst treated by high-frequency ultrasound interventional therapy were retrospectively analyzed, including 30 males and 30 females with an average age of (30.93±5.32) years old ranging from 20 to 54 years old. The course of disease ranged from 1 to 10 years with an average of (3.45±0.25) years. High-frequency ultrasound features of all patients were analyzed. The clinical efficacy, the occurrence of adverse events and the changes of psychological status before and after treatment were analyzed.In 60 cases of elbow cyst, the cyst size was from 6 mm×7 mm to 111 mm×60 mm. The characteristics of ultrasonic images included such as most of the morphology was regular, which was round or oval, and a few were irregular;the boundary was clear, there was a capsule wall, most of the inside of the capsule was good, no echo;when accompanied by bleeding or infection, small dense points can be seen floating;the cystic wall of the patients with long course of disease was coarser, and the internal light bands were separated, showing multilocular shape;no significant blood flow signal was observed. Final results involved olecranon bursa cysts in 19 cases, annular ligament cysts in 10 cases, radial bursa cysts in 9 cases, accessory ligament cysts in 7 cases, epidermoid cysts in 4 cases, ganglion cysts in 6 cases, nerve sheath cysts in 5 cases. After treatment, 33 cases were cured, 16 cases had obvious effect, 11 cases were improved, 0 cases were invalid. After treatment, mild adverse events occurred in 1 case, moderate adverse events in 1 case, and severe adverse events in 0 cases, with a total incidence of 3.33% (2/60). After treatment, positive affect score (38.04±1.74) was higher than that before treatment (35.92±2.34), and negative affect score (24.61±1.51) was lower than that before treatment (30.15±3.46), with statistical significance(P<0.05).High-frequency ultrasound has high diagnostic value for elbow cyst, and it has ideal effect in interventional therapy.
Radiation-induced brain injury is a serious complication with complex pathogenesis that may accompany radiotherapy of head and neck tumors. Although studies have shown that calcium (Ca2+) signaling may be involved in the occurrence and development of radiation-induced brain injury, the underlying molecular mechanisms are not well understood. In this study, we used real-time quantitative polymerase chain reaction and Western blotting assays to verify our previous finding using next-generation sequencing that the mRNA and protein expression levels of Orai3 in rat brain microvascular endothelial cells (rBMECs) increased after X-ray irradiation. We next explored the role of Orai3 and Orai3-mediated store-operated Ca2+ entry (SOCE) in radiation-induced brain injury. Primary cultured rBMECs derived from wild-type and Orai3 knockout (Orai3(−/−)) Sprague–Dawley rats were used for in vitro experiments. Orai3-mediated SOCE was significantly increased in rBMECs after X-ray irradiation. However, X-ray irradiation-induced SOCE increase was markedly reduced in Orai3 knockout rBMECs, and the percentage of BTP2 (a nonselective inhibitor of Orai channels)-inhibited SOCE was significantly decreased in Orai3 knockout rBMECs. Functional studies indicated that X-ray irradiation decreased rBMEC proliferation, migration, and tube formation (a model for assessing angiogenesis) but increased rBMEC apoptosis, all of which were ameliorated by BTP2. In addition, occurrences of all four functional deficits were suppressed in X-ray irradiation-exposed rBMECs derived from Orai3(−/−) rats. Cerebrovascular damage caused by whole-brain X-ray irradiation was much less in Orai3(−/−) rats than in wild-type rats. These findings provide evidence that Orai3-mediated SOCE plays an important role in radiation-induced rBMEC damage and brain injury and suggest that Orai3 may warrant development as a potential therapeutic target for reducing or preventing radiation-induced brain injury.
This study aims to explore the role of Epstein-Barr virus (EBV) miR-BART4 in occurrence and progression of nasopharyngeal carcinoma (NPC) and its effect on radiosensitivity.The expressions of EBV and miR-BART4 in 108 cases of NPC tissues and 97 cases of chronic nasopharyngeal inflammation tissues were determined by real time quantitative polymerase chain reaction (PCR), and the relationship between the expression of miR-BART4 and the clinicopathological features of NPC was analyzed. Cell lines, HONEl, CNEl, CNE2, C666-1, 6-10B, and NP-69 were used to compare the expression of miR-BART4, in which the CNE2 cells were selected for further experiments. CNE2 cells were grouped into blank group, negative control (NC) group, miR-BART4 inhibitors group and miR-BART4 mimics group. Cells in above groups were under radiation of 6 Gy X ray for 12 h before grouped into control group, 6 Gy group, NC + 6 Gy group, miR-BART4 inhibitors + 6 Gy group and miR-BART4 mimics + 6 Gy group. Cell proliferation, clone formation ability, cell apoptosis, invasion and migration ability were measured by MTT assay, clone formation assay, flow cytometry (FCM), Transwell assay and scratch test, respectively. Western blot analysis was used to detect the expression of apoptosis-related proteins (cleaved caspase-3, Bax and Bcl-2) and epithelial-mesenchymal transition (EMT) marker protein E-cadherin and Vimentin. mRNA and protein expression of PTEN were detected by qRT-PCR and western blot. Bioinformatics software and luciferase activity experiments were used to verify the targeting relationship between miR-BART4 and PTEN.Positive rate of EBV in NPC tissues (93.5%) was remarkably higher than that in chronic nasopharyngeal inflammation tissues (21.6%). miR-BART4 was highly expressed and mRNA and protein expression of PTEN was lowly expressed in EBV positive NPC tissues compared with EBV negative NPC tissues and chronic nasopharyngeal inflammation tissues. The expression of miR-BART4 was related to the clinical stage, lymph node metastasis and differentiation degree of NPC. Expression of miR-BART4 in CNE2, CNEl, HONEl, C666-1, 6-10B, 5-8F cells was higher than that in NP-69 cells. In CNE2 and C666-1 cell experiments, compared with blank group and NC group, miR-BART4 inhibitors group had decreased miR-BART4 expression, increased mRNA and protein expression of PTEN, cell survival rate, invasion and migration ability and increased cell apoptosis rate, which is totally contrary to the observation in miR-BART4 mimics group. The radiosensitive NPC tissues had higher miR-BART4 expression than that in radio-resistance NPC tissues. In comparison to 6 Gy group and NC + 6 Gy group, cell survival rate and clone number was inhibited, but the cell apoptosis rate was increased in miR-BART4 inhibitors +6 G group, in contrary to the observation in miR-BART4 inhibitors + 6 Gy group. Bioinformatics software and luciferase activity experiments confirmed that miR-BART4 could inhibit the expression of PTEN.EBV may promote development and progression of NPC by up-regulating miR-BART4 expressions, consequently inhibiting its radiosensitivity, whose effect may be related to the targeting inhibition of PTEN expression.
Colorectal cancer (CRC) is one of the major types of cancer and causes of mortality worldwide, and it remains the third most common cause of cancer‑associated mortality worldwide. MicroRNAs (miRNAs) are a class of small RNAs, which have been shown to be associated with CRC. In the present study, an MTT assay and proliferating cell nuclear antigen (PCNA) protein examination assay were performed to detect RKO cell viability. Hoechst staining, and caspase‑3 activity and BrdU incorporation assays were performed to detect RKO cell apoptosis, respectively. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analyses were used to analyze the expression of cyclooxygenase‑2 (COX‑2). Western blot analysis was also used to analyze the expression of vascular endothelial growth factor (VEGF) and mitogen‑activated protein kinase (MAPK) signal molecules, including extracellular signal‑regulated kinase (ERK), p38 and c‑Jun N‑terminal kinase (JNK). The target genes of miR-125 were predicted using a double luciferase reporter gene assay. The results of the MTT assay showed that RKO cell viability was decreased by an miRNA-125 mimic and increased by the miRNA-125 inhibitor. The RKO cell viability was significantly correlated with the expression of PCNA. The migration of RKO cells was significantly downregulated in the miR-125 mimics‑transfected cells and upregulated in the miRNA-125 inhibitor‑transfected cells. The results of Hoechst staining and the caspase‑3 activity and BrdU incorporation assays showed that RKO cell apoptosis was increased following miRNA-125 mimic transfection and decreased following miRNA-125 inhibitor transfection. The results of the RT‑qPCR and western blot analysis showed that the expression of COX‑2 was increased in the miR-125 mimic‑transfected cells and decreased in the miR-125 inhibitor‑transfected cells. Using an online miRNA target prediction database, the double luciferase reporter gene assay showed that miR‑125 targeted and inhibited the expression of VEGF through target sites located in the 3' untranslated region of VEGF mRNA. In conclusion, the abnormal expression of miR‑125 was found to be closely associated with CRC. Therefore, miR‑125 may be a novel therapeutic target for CRC.
Objective: To investigate the concentration and clinical significance of serum ferritin (SF) in patients diagnosed with advanced gastric cancer before and after treatment. Methods: Forty patients with advanced gastric cancer diagnosed by cytology or pathology in our hospital were selected, including 25 males and 15 females, aged from 48 to 85 years, and the median age was 61.0 years. 40 healthy volunteers matched with age and education were selected as the control group. In order to study the changes of SF level in the treatment of advanced gastric cancer, we divided the patients into effective group (efficacy evaluation as partial remission or complete remission), ineffective group (efficacy evaluation as no remission) and recurrence group according to the efficacy after treatment. Then the difference of SF level between different groups and the relationship between SF level and curative effect were analyzed. There was no significant difference in gender and age among all groups. Results: The SF levels in the newly diagnosed group, stage III patient group and stage IV patient group were significantly higher than those in the control group. The level of SF in stage IV patients was significantly higher than that in stage III patients. There were significant differences in SF level between the effective treatment group, the newly diagnosed group and the ineffective treatment group, but there was no significant difference in SF level between the newly diagnosed group and the ineffective treatment group. Conclusion: SF level has a certain value in the auxiliary diagnosis of gastric cancer, and it also has a certain guiding significance for the evaluation of curative effect and prognosis after treatment.
We reported a case of a symptomatic metastasis of squamous cell carcinoma of the uterine cervix (SCCUC) to the right ventricle, then to the right atrium and superior vena cava five years later than the first SCCUC diagnosis. Because of the persistent thrombocytopenia, the treatment was discontinued after only one cycle of reduced paclitaxel liposome five years ago. The patient died six weeks after the diagnosis of cardiac metastasis. We reviewed the literatures in last two decades for the epidemiology, clinical presentaion, diagnosis, treatment and prognosis of SCCUC with cardiac metastasis (SCCUCCM). Dyspnea and chest pain are the common clinical presentations. Echocardiography, cardiac computed tomography (CT) and cardiac magnetic resonance imaging (CMR) are recommended in diagnosis. The prognosis for cardiac metastasis is extremely poor, with a median survival time of 5 months. Thrombocytopenia is a negative factor in the survival time of SCCUC-CM. Aggressive therapy including surgical intervention, chemotherapy, and whole heart radiation therapy may prolong survival time.
Background: Epithelial-mesenchymal transition (EMT) is an important factor influencing hepatocellular carcinoma (HCC) cell proliferation, invasion, and metabolism, as well as an important target influencing the progression and outcome of HCC patients. However, key EMT genes and their mechanisms of action in HCC cancer cell subpopulations remain poorly understood.
Radioactive brain injury, a severe complication ensuing from radiotherapy for head and neck malignancies, frequently manifests as cognitive impairment and substantially diminishes patients' quality of life. Despite its profound impact, the pathogenesis of this condition remains inadequately elucidated, and efficacious treatments are notably absent in clinical practice. Consequently, contemporary interventions predominantly focus on symptom alleviation rather than achieving a radical cure or reversing the injury process. This article provides a comprehensive review of the various pathogenic mechanisms and therapeutic strategies associated with radioactive brain injury, offering insights that may guide the development of novel therapeutic strategies.
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