OBJECTIVE: To investigate the efficacy of chemotherapy combined with antivirals in adult T-cell leukemia/lymphoma (ATLL) patients and the prognostic factors. METHODS: Forty nine patients with previously treated or treatment-nave ATLL from January 2018 to January 2021 were included in our study. The patients were divied into two groups according to whether they received antiviral treatment, twenty-seven patients were treated with chemotherapy combined with antivirals, including thirteen patients treated with recombinant interferon alpha-2b and CHOP therapy, eight patients treated with zidovudine combined with CHOP therapy, and 6 patients treated with CHOP regimen combined with interferon and zidovudine. Twenty-two patients were treated with CHOP therapy. The changes of symptom, hematological parameters, lactic dehydrogenase, β2-microglobulin, and the Ki-67 positive rate were compared between the two groups before and after treatments. The clinical efficacy of chemotherapy combined with antiviral therapy for ATLL was evaluated. The antiviral effect was assessed by detecting HTLV-1 virus copy number, and prognostic factors were analyzed. RESULTS: The median follow-up time was 14 months. Compared with the patients treated with chemotherapy alone, the patients treated with chemotherapy combined with antivirals had lower tumor and virus loads, lower white blood cell count, lower lactate dehydrogenase level, lower β2-microglobulin lever, and lower Ki-67 positive rate (all P<0.05). The total effective rate of patients treated with chemotherapy combined with antivirals was significantly higher than those of patients treated with chemotherapy alone (63.0% vs 31.8%, P=0.035). The one-year overall survival (OS) rates of chemotherapy combined with antivirals groups and chemotherapy alone group were (74.1±2.9)％ and (40.9±2.1)％ (P=0.021), respectively. The one-year progress free survival (PFS) rates were (51.9±3.3)％ and (13.6±2.8)％ (P=0.017), respectively. Multivariable Cox regression analysis showed that HTLV-1 virus load (HR=7.518, 95%CI: 2.517-36.192, P=0.013) and antiviral therapy ［HR=5.617 (95%CI 1.803-11.293), P=0.027］ were independent prognostic factors for the long-term efficacy. CONCLUSION Addition of antivirals to chemotherapy can prolong PFS and OS in ATLL patients. HTLV-1 virus load and antiviral therapy are independent prognostic factors for ATLL patients.
Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Antiviral Agents/therapeutic use* ; Cyclophosphamide ; Doxorubicin ; Humans ; Interferon alpha-2/therapeutic use* ; Ki-67 Antigen ; Lactate Dehydrogenases ; Leukemia-Lymphoma, Adult T-Cell/drug therapy* ; Lymphoma/drug therapy* ; Oxidoreductases/therapeutic use* ; Vincristine/therapeutic use* ; Zidovudine/therapeutic use*

Animals ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drug Discovery ; Drug Evaluation, Preclinical ; Enzyme Inhibitors ; therapeutic use ; Humans ; Mice ; Molecular Structure ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; Pandemics ; Pneumonia, Viral ; drug therapy ; Pyrimidines ; biosynthesis

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

OBJECTIVETo investigate the inhibitory effect and underlying mechanism of total saponins from Paris polyphylla var. yunnanensis on the proliferation of salivary adenoid cystic carcinoma ACC-83 cells.

METHODSIn vitro cell culture was performed. The proliferation of ACC-83 cells treated with different concentrations (5, 10, 20, 40, 60, 80, 100 μg·mL⁻¹) of total saponins from Paris polyphylla var. yunnanensis was observed using CCK-8 assay. Meanwhile, the apoptosis of ACC-83 cells treated with different concentrations (25, 50, 100 μg·mL⁻¹) of the total saponins was observed using flow cytometry. The expression levels of macrophage migration inhibitory factor (MIF) and CD74 were measured using Western blot and reverse transcription-polymerase chain reaction.

RESULTSThe total saponins from Paris polyphylla var. yunnanensis induced apoptosis and expressed dose-effect relationship. ACC-83 cells expressed MIF and CD74, and the total saponins suppressed MIF and CD74 expression in ACC-83 cells.

CONCLUSIONSThe total saponins from Paris polyphylla var. yunnanensis can significantly inhibit the proliferation, suppress MIF and CD74 expression, and promote apoptosis in ACC-83 cells. This study provides a theoretical basis for the treatment of salivary adenoid cystic carcinoma using Paris polyphylla var. yunnanensis.
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Carcinoma, Adenoid Cystic ; drug therapy ; Humans ; Intramolecular Oxidoreductases ; Liliaceae ; Macrophage Migration-Inhibitory Factors ; Rhizome ; Salivary Gland Neoplasms ; drug therapy ; Saponins ; therapeutic use

OBJECTIVETo study the effect of omega-3 polyunsaturated fatty acids (omega-3 PUFA) on inflammation in lung tissue of rats with severe scald and its mechanism.

METHODSSeventy-two adult SD rats were divided into sham scald group (SS, n = 8), treatment group 1 (T1, n = 32), treatment group 2 (T2, n = 32) according to the random number table. Rats in T1 group and T2 group were inflicted with 30% TBSA full-thickness scald, and then they were respectively injected with 100 g/L omega-3 PUFA (1 mL/kg) and 200 g/L long-chain fatty acid (2 mL/kg) via tail vein within 5 minutes after burn. The above two fatty acids with equivalent calories were continuously injected for 10 days (once a day). On post burn day (PBD) 1, 4, 7, and 10, serum level of TNF-alpha and level of macrophage inflammatory protein 1alpha (MIP-lalpha) in lung homogenate of T1 and T2 groups were detected, the levels of NF-kappaBp65 and macrophage migration inhibitory factor (MIF) in lung tissue of T1 and T2 groups were observed with immunohistochemical staining (recorded as score). Above-mentioned parameters were also determined in SS group. Data were processed with t test.

RESULTSThe levels of 4 parameters in T1 and T2 groups on PBD 1, 4, 7, 10 were higher than those in SS group (with t values from 3.411 to 8.782, P values all below 0.01), and those in T1 group on PBD 4, 7, 10 were lower than those in T2 group (with t values from 2. 321 to 2.785, P values all below 0.05). The serum level of TNF-alpha and levels of MIP-1alpha, NF-kappaBp65, and MIF in lung tissue in SS group was respectively (0.96 +/- 0.32) ng/mL, (76 +/- 16) pg/mL, 0.24 +/- 0.03, 1.31 +/- 0.03, and those in T1 and T2 groups all peaked on PBD 7 [(2.43 +/- 0.32) ng/mL, (210 +/- 56) pg/mL, 4.23 +/- 2.15, 4.69 +/- 1.83; (3.15 +/- 0.54) ng/mL, (274 +/- 64) pg/mL, 5.15 +/- 2.31, 5.37 +/- 2.16].

CONCLUSIONSOmega-3 PUFA can effectively reduce serum level of TNF-alpha and levels of MIP-1alpha, NF-kappaBp65, and MIF in lung tissue of rats with severe scald, showing that it has a protective effect against injury of lung tissue.

Animals ; Burns ; metabolism ; pathology ; therapy ; Chemokine CCL3 ; metabolism ; Fatty Acids, Omega-3 ; therapeutic use ; Female ; Inflammation ; metabolism ; Intramolecular Oxidoreductases ; metabolism ; Lung ; metabolism ; Macrophage Migration-Inhibitory Factors ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; blood