INTRODUCTION

One of the novel strategies in cancer treatment is the combination of conventional chemotherapeutic drugs and natural products. In a previous study, co-treatment of the anti-cancer drug cyclophosphamide (CP) with honey from giant honey bee (Apis dorsata) resulted to a dose-dependent increase in its cytotoxic effect in human lung carcinoma (A549) cells. However, the molecular mechanism of this combinatorial effect remains unknown.

In this study, the effect of A. dorsata honey on the expression of selected CYP450 genes at the mRNA level, as well as the proapoptotic gene CASP8 and antiapoptotic gene BCL2 was investigated in CP-treated A549 cells.

MTT Assay was performed to determine the cell viability of A549 cells after treatment with CP with or without A. dorsata honey, as well as the EC50 of CP with honey thereafter. RT-qPCR was then performed to study the effect of A. dorsata honey on the expression of selected CYP450 genes as well as CASP8 and BCL2 genes in CPtreated A549 cells. LC-MS was carried out to screen for putative compounds in A. dorsata honey which may possibly have anti-cancer activity.

Honey in the lowest concentration (0.6% v/v) most effectively enhanced the cytotoxic effect of CP. CYP2J2 and CYP1B1 indicated a 2.38-fold and 1.49-fold upregulation, respectively as compared to untreated cells. This cytotoxic effect is further enhanced by upregulation of CASP8 that is paralleled by a downregulation of BCL2. Phytosphingosine and sphinganine are honey constituents which may be linked to the increased cytotoxicity of CP observed in A549 cells.

This study provides further knowledge on the molecular basis by which A. dorsata honey potentiates the cytotoxic effect of cyclophosphamide in A549 cells.

Humans ; Tenofovir/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Hepatitis B virus ; Viral Load ; Liver Neoplasms/drug therapy* ; Antiviral Agents/therapeutic use* ; Hepatitis B, Chronic/drug therapy* ; Treatment Outcome

BACKGROUND: Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China. METHODS: Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01). CONCLUSIONS Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.
Male ; Humans ; Adult ; Hepatitis B Surface Antigens ; Hepatitis B virus/genetics* ; HIV Infections/drug therapy* ; HIV ; DNA, Viral ; Incidence ; Coinfection/drug therapy* ; Retrospective Studies ; Tenofovir/therapeutic use* ; Lamivudine/therapeutic use* ; Hepatitis B, Chronic/drug therapy*

Humans ; Tenofovir/therapeutic use* ; Emtricitabine/therapeutic use* ; HIV Infections/drug therapy* ; Anti-HIV Agents/therapeutic use*

Humans ; HIV Infections/drug therapy* ; HIV-1/genetics* ; Tenofovir/therapeutic use* ; Anti-HIV Agents/therapeutic use* ; RNA ; Drug Combinations

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.
Humans ; Antiretroviral Therapy, Highly Active/adverse effects* ; Anti-HIV Agents/adverse effects* ; HIV Infections/drug therapy* ; Tenofovir/therapeutic use* ; Retrospective Studies ; Emtricitabine/pharmacology* ; Adenine/therapeutic use* ; Lipids

This study aims to investigate the effects of Blaps rynchopetera Fairmaire and/or cyclophosphamide on the proliferation and apoptosis of lung cancer cells and decipher the underlying mechanism. B. rynchopetera and cyclophosphamide-containing serum and blank serum were prepared from SD rats. Cell counting kit-8(CCK-8) assay was employed to examine the proliferation of lung cancer cell lines A549 and Lewis treated with corresponding agents. The Jin's formula method was used to evaluate the combined effect of the two drugs. According to the evaluation results, appropriate drug concentrations and lung cancer cell line were selected for subsequent experiments, which included control, B. rynchopetera, cyclophosphamide, B. rynchopetera + cyclophosphamide, and B. rynchopetera + Wnt/β-catenin pathway agonist lithium chloride(LiCl) groups. Immunocytochemistry was employed to measure the expression of proliferation-related proteins in Lewis cells after drug interventions. Flow cytometry was employed to determine the cell cycle and apoptosis. The expression levels of proliferating cell nuclear antigen(PCNA), cyclinD1, B-cell lymphoma 2(Bcl-2), Bcl-2-assiocated X protein(Bax), Wnt1, and β-catenin were determined by Western blot. The results showed that B. rynchopetera and/or cyclophosphamide significantly inhibited the proliferation of A549 and Lewis cells. Compared with B. rynchopetera alone, the combination increased the inhibition rate on cell proliferation. The combination of B. rynchopetera and cyclophosphamide demonstrated a synergistic effect according to Jin's formula-based evaluation. Compared with the control group, the B. rynchopetera, cyclophosphamide, and B. rynchopetera + cyclophosphamide groups showed increased proportion of Lewis cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. Compared with the cyclophosphamide group, the combination group showed increased proportion of cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. Compared with the B. rynchopetera group, the B. rynchopetera + LiCl group had deceased proportion of cells in G_0/G_1 phase, decreased apoptosis rate, down-regulated expression of Bax, and up-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. The results indicated that B. rynchopetera could inhibit the proliferation, arrest the cell cycle, and induce the apoptosis of lung cancer cells by inhibiting the Wnt/β-catenin signaling pathway. Moreover, B. rynchopetera had a synergistic effect with cyclophosphamide.
Rats ; Animals ; Wnt Signaling Pathway ; Lung Neoplasms/genetics* ; beta Catenin/metabolism* ; Proliferating Cell Nuclear Antigen ; bcl-2-Associated X Protein/metabolism* ; Rats, Inbred Lew ; Rats, Sprague-Dawley ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Proliferation ; Cyclophosphamide ; Cell Line, Tumor

OBJECTIVES: To investigate the difference in the therapeutic effect of mycophenolate mofetil (MMF) or cyclophosphamide (CTX) in children with Henoch-Schönlein purpura nephritis (HSPN) of different age groups. METHODS: A retrospective analysis was conducted on the clinical data of 135 children with HSPN who were treated with MMF or CTX in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from October 2018 to October 2020. According to the immunosuppressant used, they were divided into two groups: MMF group and CTX group, and according to the age, each group was further divided into two subgroups: ≤12 years and >12 years, producing four groups, i.e, the ≤12 years MMF subgroup (n=30), the >12 years MMF subgroup (n=15), the ≤12 years CTX subgroup (n=71), and the >12 years CTX subgroup (n=19). All children were followed up for at least 12 months, and the above groups were compared in terms of clinical outcomes and the incidence rate of adverse reactions. RESULTS: There was no significant difference in the complete response rate between the MMF group and the CTX group after 3, 6, and 12 months of treatment (P>0.05). There were no significant difference in the complete response rate and the incidence rate of adverse reactions between the >12 years MMF subgroup and the ≤12 years MMF subgroup at 3, 6, and 12 months of treatment (P>0.05). The >12 years CTX subgroup had a significantly lower complete response rate than the ≤12 years CTX subgroup at 6 and 12 months of treatment (P<0.05). The >12 years CTX subgroup had a significantly higher incidence rate of adverse reactions than the >12 years MMF subgroup (P<0.05). CONCLUSIONS The efficacy and adverse reactions of MMF are not associated with age, but the efficacy of CTX is affected by age, with a higher incidence rate of adverse reactions. CTX should be selected with caution for children with HSPN aged >12 years.
Child ; Humans ; Mycophenolic Acid/adverse effects* ; IgA Vasculitis/drug therapy* ; Retrospective Studies ; Cyclophosphamide/adverse effects* ; Immunosuppressive Agents/adverse effects* ; Vasculitis/drug therapy* ; Nephritis/complications*

OBJECTIVE: To compare the efficacy of plerixafor (PXF) combined with granulocyte colony-stimulating factor (G-CSF) (PXF+G-CSF) and cyclophosphamide (Cy) combined with G-CSF (Cy+G-CSF) in the mobilization of peripheral blood stem cells (PBSCs) in patients with multiple myeloma (MM). METHODS: The clinical data of 41 MM patients who underwent PBSC mobilization using PXF+G-CSF (18 cases) or Cy+G-CSF (23 cases) in Shanxi Bethune Hospital from January 2019 to December 2021 were retrospectively analyzed, including the count of collected CD34⁺ cells, acquisition success rate, failure rate, and optimal rate. The correlation of sex, age, disease type, DS staging, ISS staging, number of chemotherapy cycle, disease status before mobilization, and mobilization regimen with the collection results was analyzed, and the adverse reactions, length of hospital stay, and hospitalization costs were compared between the two mobilization regimens. RESULTS: The 41 patients underwent 97 mobilization collections, and the median number of CD34⁺ cells collected was 6.09 (0-34.07)×10⁶/kg. The acquisition success rate, optimal rate, and failure rate was 90.2%, 56.1%, and 9.8%, respectively. Univariate analysis showed that sex, age, disease type, and disease stage had no significant correlation with the number of CD34⁺ cells collected and acquisition success rate (P >0.05), but the patients with better disease remission than partial remission before mobilization were more likely to obtain higher CD34⁺ cell count (P <0.05). The PXF+G-CSF group had a larger number of CD34⁺ cells and higher acquisition success rate in the first collection than Cy+G-CSF group (both P <0.05), and had lower infection risk and shorter length of hospital stay during mobilization (both P <0.05), but the economic burden increased (P <0.05). CONCLUSION PXF+G-CSF used for PBSC mobilization in MM patients has high first acquisition success rate, large number of CD34⁺ cells, less number of collection times, and short length of hospital stay, but the economic cost is heavy.
Humans ; Antigens, CD34/metabolism* ; Cyclophosphamide/therapeutic use* ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Hematopoietic Stem Cell Transplantation ; Heterocyclic Compounds/therapeutic use* ; Multiple Myeloma/drug therapy* ; Peripheral Blood Stem Cells/metabolism* ; Retrospective Studies

OBJECTIVE: To evaluate the efficacy and safety of etoposide combined with cyclophosphamide (EC) regimen for mobilization of autologous peripheral blood stem cells (APBSCs) in patients with multiple myeloma (MM). METHODS: The clinical data of 48 MM patients who received APBSC transplantation (APBSCT) in Department of Hematology of the First Affiliated Hospital of Nanchang University from January 2015 to October 2021 were retrospectively analyzed. The mobilization success rate and mobilization optimal rate of EC regimen were counted, and its effect on transplant efficacy, adverse reactions, hematopoietic reconstitution after transplantation, and survival time of MM patients were analyzed. RESULTS: APBSCs were collected on day 14 (10-19) after EC administration. The median of collected CD34⁺ cells was 6.82 (1.27-22.57)×10⁶/kg, and the median number of apheresis session was 2 (1-4). The mobilization success rate (collecting CD34⁺ cells≥2×10⁶ cells/kg after completion of apheresis) was 98% (47/48), and mobilization optimal rate (collecting CD34⁺ cells≥5×10⁶ cells/kg after completion of apheresis) was 71% (34/48). The depth of remission were improved after APBSCT, and the complete remission (CR) rate increased from 45.8% before transplantation to 87.5% after transplantation (P <0.01). There was no transplant-related death, no blood transfusion during mobilization, and no mucositis occurred in the patients. The most common complication was neutropenia, with an incidence of 75.0% (36/48). After transplantation, all the patients successfully achieved hematopoietic reconstitution. The median time to neutrophil engraftment was 10 (9-26) days, and median time to platelet engraftment was 10 (8-33) days. By the end of follow-up, both the median progression-free survival (PFS) and overall survival (OS) time were not reached. The 5-year estimated PFS rate and OS rate was 53.8% and 82.4%, respectively. CONCLUSION The EC regimen for mobilization of APBSC has a high acquisition success rate and controllable adverse reactions, which can be an effective and safe mobilization regimen in MM patients.
Humans ; Multiple Myeloma/therapy* ; Etoposide/therapeutic use* ; Peripheral Blood Stem Cells ; Hematopoietic Stem Cell Mobilization/adverse effects* ; Retrospective Studies ; Granulocyte Colony-Stimulating Factor ; Cyclophosphamide/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Transplantation, Autologous/adverse effects*