In vivo studies could not confirm in vitro prophylactic synergism between Moringa essential oil and Lactobacillus reuteri (MT180537)

Abstract Aerobic vaginitis (AV) is a recently defined vaginal recurring infection, which is treated with antibiotics. However, excessive and prolonged use of antibiotics disrupts healthy vaginal microflora and leads to the emergence of antibiotic resistance among pathogens. This situation has directed researchers to explore alternative antimicrobials. The current study describes in vitro and in vivo antimicrobial efficacy and pharmaceutical interactions between plant essential oils (EOs) and five lactic acid bacteria (LABs), isolated from the healthy vagina, against E. faecalis, one of the major etiological agents of AV. In vitro experiments confirm good antimicrobial activity of both plant EOs and cell free supernatant (CFS) from LABs. Based on high antimicrobial efficacy, Moringa essential oil (MO) was selected to determine its nature of interaction with CFS of five LAB strains. Synergism was recorded between MO and CFS of L. reuteri (MT180537). To validate in vitro findings, prophylactic responses of individual and synergistic application of MO and L. reuteri (MT180537) were evaluated in an E. faecalis (MW051601) induced AV murine model. The prophylactic efficacy was evidenced by a reduction in intensity of clinical symptoms, E. faecalis (MW051601) count per vaginal tissue along with a reduction in AV associated changes in histological markers of infection in animals receiving Moringa essential oil and L. reuteri (MT180537) alone or in combination. However, significant synergism between Moringa essential oil and L. reuteri (MT180537) could not be observed. Our data confirms the importance of in vivo experiments in deducing pharmacological interactions.

Resumo Vaginite aeróbica (VA) é uma infecção vaginal recorrente definida recentemente, que é tratada com antibióticos. No entanto, o uso excessivo e prolongado de antibióticos perturba a microflora vaginal saudável e leva ao surgimento de resistência aos antibióticos entre os patógenos. Esta situação levou os pesquisadores a explorar antimicrobianos alternativos. O presente estudo descreve a eficácia antimicrobiana in vitro e in vivo e as interações farmacêuticas entre óleos essenciais vegetais (OE) e cinco bactérias lácticas (BAL), isoladas de vagina sã, contra E. faecalis, um dos principais agentes etiológicos da AV. Os experimentos in vitro confirmam a boa atividade antimicrobiana de ambos os EOs de plantas e sobrenadante livre de células (CFS) de LABs. Com base na alta eficácia antimicrobiana, o óleo essencial de Moringa (MO) foi selecionado para determinar sua natureza de interação com o sobrenadante livre de células (CFS) de cinco cepas de LAB. Sinergismo foi registrado entre MO e CFS de L. reuteri (MT180537). Para validar os resultados in vitro, as respostas profiláticas da aplicação individual e sinérgica de MO e L. reuteri (MT180537) foram avaliadas em um modelo murino AV induzido por E. faecalis (MW051601). A eficácia profilática foi evidenciada por uma redução na intensidade dos sintomas clínicos, contagem de E. faecalis (MW051601) por tecido vaginal, juntamente com uma redução nas alterações associadas a AV nos marcadores histológicos de infecção em animais que receberam óleo essencial de Moringa e L. reuteri (MT180537) sozinho ou em combinação. No entanto, não foi possível observar sinergismo significativo entre o óleo essencial de Moringa e L. reuteri (MT180537). Nossos dados confirmam a importância dos experimentos in vivo na dedução de interações farmacológicas.

In vivo studies could not confirm in vitro prophylactic synergism between Moringa essential oil and Lactobacillus reuteri (MT180537) / Estudos in vivo não puderam confirmar o sinergismo profilático in vitro entre o óleo essencial de Moringa e Lactobacillus reuteri (MT180537)

Aerobic vaginitis (AV) is a recently defined vaginal recurring infection, which is treated with antibiotics. However, excessive and prolonged use of antibiotics disrupts healthy vaginal microflora and leads to the emergence of antibiotic resistance among pathogens. This situation has directed researchers to explore alternative antimicrobials. The current study describes in vitro and in vivo antimicrobial efficacy and pharmaceutical interactions between plant essential oils (EOs) and five lactic acid bacteria (LABs), isolated from the healthy vagina, against E. faecalis, one of the major etiological agents of AV. In vitro experiments confirm good antimicrobial activity of both plant EOs and cell free supernatant (CFS) from LABs. Based on high antimicrobial efficacy, Moringa essential oil (MO) was selected to determine its nature of interaction with CFS of five LAB strains. Synergism was recorded between MO and CFS of L. reuteri (MT180537). To validate in vitro findings, prophylactic responses of individual and synergistic application of MO and L. reuteri (MT180537) were evaluated in an E. faecalis (MW051601) induced AV murine model. The prophylactic efficacy was evidenced by a reduction in intensity of clinical symptoms, E. faecalis (MW051601) count per vaginal tissue along with a reduction in AV associated changes in histological markers of infection in animals receiving Moringa essential oil and L. reuteri (MT180537) alone or in combination. However, significant synergism between Moringa essential oil and L. reuteri (MT180537) could not be observed. Our data confirms the importance of in vivo experiments in deducing pharmacological interactions.

Vaginite aeróbica (VA) é uma infecção vaginal recorrente definida recentemente, que é tratada com antibióticos. No entanto, o uso excessivo e prolongado de antibióticos perturba a microflora vaginal saudável e leva ao surgimento de resistência aos antibióticos entre os patógenos. Esta situação levou os pesquisadores a explorar antimicrobianos alternativos. O presente estudo descreve a eficácia antimicrobiana in vitro e in vivo e as interações farmacêuticas entre óleos essenciais vegetais (OE) e cinco bactérias lácticas (BAL), isoladas de vagina sã, contra E. faecalis, um dos principais agentes etiológicos da AV. Os experimentos in vitro confirmam a boa atividade antimicrobiana de ambos os EOs de plantas e sobrenadante livre de células (CFS) de LABs. Com base na alta eficácia antimicrobiana, o óleo essencial de Moringa (MO) foi selecionado para determinar sua natureza de interação com o sobrenadante livre de células (CFS) de cinco cepas de LAB. Sinergismo foi registrado entre MO e CFS de L. reuteri (MT180537). Para validar os resultados in vitro, as respostas profiláticas da aplicação individual e sinérgica de MO e L. reuteri (MT180537) foram avaliadas em um modelo murino AV induzido por E. faecalis (MW051601). A eficácia profilática foi evidenciada por uma redução na intensidade dos sintomas clínicos, contagem de E. faecalis (MW051601) por tecido vaginal, juntamente com uma redução nas alterações associadas a AV nos marcadores histológicos de infecção em animais que receberam óleo essencial de Moringa e L. reuteri (MT180537) sozinho ou em combinação. No entanto, não foi possível observar sinergismo significativo entre o óleo essencial de Moringa e L. reuteri (MT180537). Nossos dados confirmam a importância dos experimentos in vivo na dedução de interações farmacológicas.

Research progress on ferroptosis in radiosensitivity of malignant tumors / 中华放射肿瘤学杂志

As one of the most effective treatments for cancer, radiotherapy(RT)can eliminate the tumor cells and improve the survival rate of cancer patients. However, radiation resistance of tumor cells remarkably reduces the efficacy of RT. Therefore, it is significant to investigate the resistance mechanism and explore corresponding therapy for cancer. Ferroptosis is a novel mode of programmed cell death. Numerous studies have indicated an intimate connection between ferroptosis and tumor radiosensitivity. The mechanism involves lipid reactive oxygen species accumulation, glutathione metabolism and iron metabolism. It has been reported that ferroptosis inducers can act effectively and synergistically with RT, promote radiosensitivity and further improve tumor prognosis. In this article, relevant mechanisms and research progress were reviewed, and the future development direction of this field was discussed, aiming to provide reference for clinical trials and mechanism research of RT for malignant tumors.

Research progress of magnetic hyperthermia based on magnetic nanomaterials / 中华放射肿瘤学杂志

Thermotherapy has become another important tumor treatment after surgery, radiotherapy, chemotherapy, and targeted treatment. Magnetic hyperthermia (MH) is a new type of hyperthermia, which has attracted widespread attention due to its advantages of non-invasiveness / minimal invasiveness, high efficiency and good tissue penetration. It provides a new option for the molecular level treatment of malignant tumors with high efficacy and low toxicity, which has become a new research direction of tumor treatment. Magnetic materials and suitable magnetic fields are needed to realize MH. Iron oxide nanoparticles (IONs) are widely studied as MH agents because of their high biocompatibility and heating ability. In this article, the research progress on magnetic iron oxide nanomaterials and MH combined with antitumor therapy based on magnetic nanoparticles were analyzed, and the potential application of MH in cancer treatment was reviewed.

Protective effects of WR-2721 combined with lentinan and cytokines against radiation damage / 中国辐射卫生

@#<b>Objective</b> To investigate the synergistic protective effects of WR-2721 combined with lentinan and cytokines against radiation damage in mice, and to provide a new treatment for acute radiation injury. <b>Methods</b> Seventy Institute of Cancer Research mice were divided into seven groups: a control group, a model group, WR-2721 group, Lentinan & cytokine group, WR-2721 & Lentinan group, WR-2721 & cytokine group and WR-2721 & Lentinan & cytokine group. All groups except the control group were irradiated with ⁶⁰Co γ-rays at a dose rate of 0.8 Gy/min and a cumulative dose of 5.0 Gy. The mice were sacrificed by cervical dislocation 14 d after irradiation to measure their spleen index, thymus index, and serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-11 (IL-11), and tumor necrosis factor-alpha (TNF-α). <b>Results</b> For the mice treated with WR-2721, lentinan, and cytokines, the spleen index was 7.33 ± 2.84, the thymus index was 1.70 ± 0.30, the serum SOD level was 114.0 ± 8.3, the MDA level was 7.33 ± 1.16, the IL-11 level was 155.8 ± 49.4, and the TNF-α level was 174.0 ± 37.8. All these indicators except the spleen index in the combination group significantly differed from those of the model group (<i>P</i> < 0.05 or 0.01), indicating the combined treatment promoted recovery from radiation damage. <b>Conclusion</b> WR-2721 combined with lentinan and cytokines has significant synergistic protective effects, which is a promising treatment for acute radiation injury.

Inhibitory effects of gemcitabine hydrochloride combined with ferroptosis inducers on the proliferation of PANC-1 cells / 药学实践杂志

Objective To study the effects of three ferroptosis inducers Erastin (Era), sulfasalazine (SASP) and artesunate (Art) alone or combined with gemcitabine hydrochloride (hcGEM) on the proliferation inhibition of Human pancreatic cell line PANC -1. Methods The CCK-8 method was used to detect the inhibitory effects of different concentrations of Era, SASP and Art alone or combined with hcGEM on the proliferation of PANC-1, and the combination index (CI) was used to judge whether three ferroptosis inducers combined with hcGEM had synergistic inhibitory effect on PANC-1. Results The three ferroptosis inducers and hcGEM alone or in combination could significantly inhibit the activity of PANC-1. The inhibitory effects were enhanced with the concentration increasing. The CI values of hcGEM-Era 4∶1 or 1∶4 combination group and hcGEM-SASP 1∶400 combination group were less than 1.The CI values of hcGEM-Art 1∶4 or 1∶16 combination group were less than 1 only within a certain concentration range. Conclusion The inhibitory effects of the three ferroptosis inducers and hcGEM alone or in combination were dose-dependent. The combination of hcGEM and three ferroptosis inducers could synergistically inhibit the proliferation of PANC-1.

Application of nurse led collaborative integrated nursing model in children undergoing hypospadias surgery / 中国实用护理杂志

Objective:To explore the effect of nurse led cooperative integrated nursing model in children with hypospadias, provide reference for the integration of collaborative medical care and patient care, improve the nursing level of nurses and the quality of child care.Methods:By adopting a quasi experimental study method, from January 2020 to December 2021, the clinical data of 84 male children undergoing hypospadias surgery in the Department of Urology, Children ′s Hospital of Nanjing Medical University were retrospectively analyzed, and 84 accompanying staff were included in the study. Among them, 42 children admitted from January to December 2020 and 42 accompanying staff served as the control group, and 42 children admitted from January to December 2021 and 42 accompanying staff served as the intervention group. The control group adopted the routine perioperative nursing mode, and the intervention group adopted the nurse-led collaborative integrated nursing mode. The anxiety and satisfaction of the caregivers in the two groups, the medical fear, medical compliance and postoperative pain of the children in the two groups, and the incidence of postoperative complications of the children in the two groups were compared. Results:After intervention, the satisfaction score of the intervention group ′s accompanying staff and the score of the patient ′s medical compliance were (96.46 ± 3.27) and (2.93 ± 0.89) points. The control group ′s scores were (85.24 ± 5.71) and (1.75 ± 0.63) points. The differences between the two groups were statistically significant ( t=9.52, -8.40, both P<0.05). The anxiety score of the accompanying staff in the intervention group was (44.33 ± 2.43) points, and the medical fear score and postoperative pain score of the patients were (20.76 ± 2.92) and (3.06 ± 0.57) points, respectively. The control group′s scores were (67.11 ± 3.36), (33.58 ± 3.84) and (6.24 ± 0.71) points, respectively. The differences between the two groups were statistically significant ( t=23.47, 12.51, 22.66, all P<0.05). The total incidence of postoperative complications in the intervention group was 4.76% (2/42), while in the control group was 52.38% (22/42). The difference was statistically significant ( χ2=23.33, P<0.05). Conclusions:The nurse led collaborative integrated nursing mode has a positive effect on relieving the negative emotions of caregivers and children, improving the satisfaction of hospitalization, improving the quality of care for children, and reducing the incidence of postoperative complications of children.

Evolution and development of potent monobactam sulfonate candidate IMBZ18g as a dual inhibitor against MDR Gram-negative bacteria producing ESBLs

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

The traditional Chinese medicines treat chronic heart failure and their main bioactive constituents and mechanisms

Chronic heart failure (CHF) is a severe public health problem with increasing morbidity and mortality, any treatment targeting a single session is insufficient to tackle this. CHF is characterized by reduced cardiac output resulting from neurohumoral dysregulation and cardiac remodeling, which might be related to oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, autophagy, mitochondrial function, and angiogenesis. These molecular mechanisms interact with each other through crosstalk. Historically, Chinese medicinal herbs have been widely applied in the treatment of CHF, and therapeutic effects of Chinese medicinal herbs and their ingredients have been scientifically confirmed over the past decades. Traditional Chinese medicine (TCM) with multiple components can confront the different pathogenesis of CHF through multiple targets. This review analyzes commonly used TCM patent drugs and TCM decoctions that are applicable to different stages of CHF based on clinical trials. Diverse bioactive ingredients in Chinese medicinal herbs have been found to treat CHF via multiple molecular mechanisms. This review comprehensively covers the key works on the effects and underlying mechanisms of TCM, herbal ingredients and synergistic effects of constituent compatibility in treating CHF, providing additional ideas to address this threat.

Recent advances in diverse nanosystems for nitric oxide delivery in cancer therapy

Gas therapy has been proven to be a promising and advantageous treatment option for cancers. Studies have shown that nitric oxide (NO) is one of the smallest structurally significant gas molecules with great potential to suppress cancer. However, there is controversy and concern about its use as it exhibits the opposite physiological effects based on its levels in the tumor. Therefore, the anti-cancer mechanism of NO is the key to cancer treatment, and rationally designed NO delivery systems are crucial to the success of NO biomedical applications. This review summarizes the endogenous production of NO, its physiological mechanisms of action, the application of NO in cancer treatment, and nano-delivery systems for delivering NO donors. Moreover, it briefly reviews challenges in delivering NO from different nanoparticles and the issues associated with its combination treatment strategies. The advantages and challenges of various NO delivery platforms are recapitulated for possible transformation into clinical applications.

Inhibitory effects of simeprevir on Staphylococcusepidermidis and itsbiofilm in vitro / 中南大学学报(医学版)

OBJECTIVES@#Staphylococcus epidermidis (S. epidermidis) is a Gram-positive opportunistic pathogen that often causes hospital infections. With the abuse of antibiotics, the resistance of S. epidermidis gradually increases, and drug repurposing has become a research hotspot in the treating of refractory drug-resistant bacterial infections. This study aims to study the antimicrobial and antibiofilm effects of simeprevir, an antiviral hepatitis drug, on S. epidermidis in vitro.@*METHODS@#The micro-dilution assay was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of simeprevir against S. epidermidis. Crystal violet staining assay was used to detect the biofilm inhibitory effect of simeprevir. The antimicrobial activity of simeprevir against S. epidermidis and its biofilm were explored by SYTO9/PI fluorescent staining. The combined effect between simeprevir and gentamycin was assessed by checkerboard assay and was confirmed by time-inhibition assay.@*RESULTS@#Simeprevir showed significant antimicrobial effects against S. epidermidis type strains and clinical isolates with the MIC and MBC at 2-16 μg/mL and 4-32 μg/mL, respectively. The antimicrobial effects of simeprevir were confirmed by SYTO9/PI staining. Simeprevir at MIC could significantly inhibit and break the biofilm on cover slides. Similarly, simeprevir also significantly inhibit the biofilm formation on the surface of urine catheters either in TSB [from (0.700±0.020) to (0.050±0.004)] (t=54.03, P<0.001), or horse serum [from (1.00±0.02) to (0.13±0.01)] (t=82.78, P<0.001). Synergistic antimicrobial effect was found between simeprevir and gentamycin against S. epidermidis with the fractional inhibitory concentration index of 0.5.@*CONCLUSIONS@#Simeprevir shows antimicrobial effect and anti-biofilm activities against S. epidermidis.

Synergistic effect of β-thujaplicin and tigecycline against tet(X4)-positive Escherichia coli in vitro / 生物工程学报

The widespread of tigecycline resistance gene tet(X4) has a serious impact on the clinical efficacy of tigecycline. The development of effective antibiotic adjuvants to combat the looming tigecycline resistance is needed. The synergistic activity between the natural compound β-thujaplicin and tigecycline in vitro was determined by the checkerboard broth microdilution assay and time-dependent killing curve. The mechanism underlining the synergistic effect between β-thujaplicin and tigecycline against tet(X4)-positive Escherichia coli was investigated by determining cell membrane permeability, bacterial intracellular reactive oxygen species (ROS) content, iron content, and tigecycline content. β-thujaplicin exhibited potentiation effect on tigecycline against tet(X4)-positive E. coli in vitro, and presented no significant hemolysis and cytotoxicity within the range of antibacterial concentrations. Mechanistic studies demonstrated that β-thujaplicin significantly increased the permeability of bacterial cell membranes, chelated bacterial intracellular iron, disrupted the iron homeostasis and significantly increased intracellular ROS level. The synergistic effect of β-thujaplicin and tigecycline was identified to be related to interfere with bacterial iron metabolism and facilitate bacterial cell membrane permeability. Our studies provided theoretical and practical data for the application of combined β-thujaplicin with tigecycline in the treatment of tet(X4)-positive E. coli infection.

Guanxinning Tablet and their active substances alleviate ox-LDL-induced endothelial cell injury / 药学学报

This study investigated the intervention effect of Guanxinning Tablet on human umbilical vein endothelial cells (HUVECs) injury induced by oxidized low density lipoprotein (ox-LDL), providing experimental basis for Guanxinning Tablet in the treatment of atherosclerosis-related diseases. Under the damage of HUVECs by ox-LDL, the cell viability was detected by CCK-8 (cell counting kit-8) assay; lactate dehydrogenase (LDH) in the cell culture supernatant was detected by the corresponding kit; the cell morphology of different groups was observed by common phase contrast microscope; reactive oxygen species (ROS) and NO levels in the cells were detected by DCFH-DA and DAF-FM DA probes, respectively; monocyte adhesion assay was used to detect the recruitment of THP-1 in HUVECs, and TMRM dye was used to detect the level of mitochondrial membrane potential; interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) secretion in the cells was detected by ELISA assay. The results showed that Guanxinning Tablet had a concentration-dependent proliferative effect on HUVECs. Under the stimulation of 100 μg·mL-1 ox-LDL, the morphology of endothelial cells was significantly changed. At this time, NO level was significantly decreased, ROS level was significantly increased and accompanied by a decrease in mitochondrial membrane potential. The recruitment of THP-1 cells by endothelial cells and IL-6, ICAM-1 and MCP-1 were also significantly increased, resulting in oxidative stress and inflammatory injury. Guanxinning Tablet and its composed extracts could significantly improve cell morphology, increase NO level, decrease ROS production, and also reduce the secretion of inflammation-related proteins IL-6 and MCP-1. Salvia miltiorrhiza and Ligusticum striatum DC. have significant synergistic effects on NO. Among them, salvianolic acid B and salvianic acid A exerted the main effects, and the combined efficacy of salvianic acid A and ferulic acid was superior to that of single administration. The above results showed that Guanxinning Tablet and their active substances had the effects of improving endothelial basal function, resisting oxidative stress, and alleviating inflammatory injury, and Salvia miltiorrhiza and Ligusticum striatum DC. synergized, which may be related to their regulation of oxidative stress and inflammation and have application prospects in the treatment of atherosclerosis-related diseases.

Joint effects of meteorological factors and PM2.5 on age-related macular degeneration: a national cross-sectional study in China

BACKGROUND@#Weather conditions are a possible contributing factor to age-related macular degeneration (AMD), a leading cause of irreversible loss of vision. The present study evaluated the joint effects of meteorological factors and fine particulate matter (PM2.5) on AMD.@*METHODS@#Data was extracted from a national cross-sectional survey conducted across 10 provinces in rural China. A total of 36,081 participants aged 40 and older were recruited. AMD was diagnosed clinically by slit-lamp ophthalmoscopy, fundus photography, and spectral domain optical coherence tomography (OCT). Meteorological data were calculated by European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis and were matched to participants' home addresses by latitude and longitude. Participants' individual PM2.5 exposure concentrations were calculated by a satellite-based model at a 1-km resolution level. Multivariable-adjusted logistic regression models paired with interaction analysis were performed to investigate the joint effects of meteorological factors and PM2.5 on AMD.@*RESULTS@#The prevalence of AMD in the study population was 2.6% (95% CI 2.42-2.76%). The average annual PM2.5 level during the study period was 63.1 ± 15.3 µg/m3. A significant positive association was detected between AMD and PM2.5 level, temperature (T), and relative humidity (RH), in both the independent and the combined effect models. For PM2.5, compared with the lowest quartile, the odds ratios (ORs) with 95% confidence intervals (CIs) across increasing quartiles were 0.828 (0.674,1.018), 1.105 (0.799,1.528), and 2.602 (1.516,4.468). Positive associations were observed between AMD and temperature, with ORs (95% CI) of 1.625 (1.059,2.494), 1.619 (1.026,2.553), and 3.276 (1.841,5.830), across increasing quartiles. In the interaction analysis, the estimated relative excess risk due to interaction (RERI) and the attributable proportion (AP) for combined atmospheric pressure and PM2.5 was 0.864 (0.586,1.141) and 1.180 (0.768,1.592), respectively, indicating a synergistic effect between PM2.5 and atmospheric pressure.@*CONCLUSIONS@#This study is among the first to characterize the coordinated effects of meteorological factors and PM2.5 on AMD. The findings warrant further investigation to elucidate the relationship between ambient environment and AMD.

Synergistic mechanisms of ferroptosis in anaplastic thyroid cancer induced by dihydroartemisinin and sorafenib / 中华内分泌代谢杂志

Objective:To investigate the synergistic effects and molecular mechanisms of dihydroartemisinin(DHA) and sorafenib(SOR) in inducing ferroptosis in anaplastic thyroid cancer(ATC) cells.Methods:CCK-8 and flow cytometry assays were performed to detect the effects of DHA and SOR on the proliferation and ferroptosis of ATC cells(CAL-62). Real-time fluorescence quantitative PCR and Western blotting assays were performed to detect the expressions of ferroptosis-related genes glutathione peroxidase 4(GPX4), solute carrier family 7 member 11 gene(SCL7A11), lipoxygenase-15(LOX-15), and p53. The levels of iron death intermediate metabolites including lactate dehydrogenase(LDH), glutathione(GSH), malondialdehyde(MDA), ferrous ion(Fe 2+ ), nitric oxide(NO), and reactive oxygen species(ROS)were measured by corresponding assay kits. The corresponding inhibition of DHA and SOR on ATC in vivo was analyzed in a tumor model in nude mice. Results:Compared with the control group, DHA, SOR, and DHA+ SOR treatment significantly inhibited cell proliferation and apoptosis in a dose-dependent manner( P<0.001), with increased LDH, Fe 2+, MDA, and ROS contents and reduced GSH activity( P<0.001), which were promoted by ferrous sulfate(FeSO 4)and reversed by ferroptosis inhibitor-1. Compared with the control group and the drug monotherapy group, 15-LOX-2 and p53 expressions were upregulated in DHA+ SOR group while GPX4 and SCL7A11 expressions were decreased( P<0.001), without significant difference in 15-LOX-1 protein content. In addition, NO level was significantly increased in DHA+ SOR group( P<0.001). DHA and SOR inhibited tumor growth of ATC in vivo. Conclusion:DHA and SOR synergistically induced ferroptosis via upregulating the expression of 15-LOX-2 gene and inhibiting NO synthesis in ATC cells.

Fas cell surface death receptor/Fas ligand genetic variants in gastric cancer patients: A case-control study

Background & objectives: Various studies have suggested a correlation between Fas cell surface death receptor/Fas ligand (FAS/FASL) variants and multiple types of cancers. The present study aimed to investigate the association between FAS-670A/G and FASL-844C/T and the synergistic effects of both variants on the risk of gastric cancer (GC) in the Kurdish population of west of Iran. Methods: This study was conducted by polymerase chain reaction-restriction fragment length polymorphism technique using MvaI and BsrDI restriction enzymes in 98 GC patients and 103 healthy control individuals. Results: According to the obtained results, a significant association (P=0.008) of FASL polymorphism among GC patients and the control group was detected. Furthermore, no significant differences were found in the FAS polymorphism frequencies between GC patients and the control group. Codominant and dominant models in FASL polymorphism showed significant protective effects against GC [odds ratio (OR)=0.307, 95% confidence interval (CI) (0.134-0.705), P=0.005; OR=0.205, 95% CI (0.058-0.718), P=0.013 and OR=0.295, 95% CI (0.129-0.673), P=0.004 for models of codominant CC vs. CT, codominant CC vs. TT and dominant, respectively]. Furthermore, the presence of both FAS-670G and FASL-844T alleles represented a significant protective effect against GC occurrence [OR=0.420, 95% CI (0.181-0.975), P=0.043]. Interpretation & conclusions: So far, we believe this is the first study, the results of which suggest that FASL gene variation and its synergistic effects with FAS gene could be associated with the risk of GC in the Kurdish population in the west of Iran

Antifungal activity study on HDAC inhibitor Rocilinostat / 药学实践杂志

Objective To evaluate the in vitro synergistic antifungal activity of HDAC inhibitors in combination with azole drugs against azoles-resistant Candida strains. Methods The checkerboard microdilution method was used to evaluate the antifungal activity of the HDAC inhibitors in combination with azole drugs against clinically drug-resistant strains. The fungistatic activity and toxicity of Rocilinostat was determined through time-growth curve assay and cytotoxicity assay. Results The compound Rocilinostat combined with azole drugs showed excellent synergistic antifungal activity against a variety of azoles-resistant Candida albicans and Candida glabrata. The combination of high concentration Rocilinostat with FLC exhibited fungistatic effects. Very low toxicity was detected with Rocilinostat towards normal cells. Rocilinostat showed better HDAC inhibitory activity than SAHA. Conclusion As a fungi HDAC inhibitor, Rocilinostat has excellent in vitro synergistic antifungal activity and no severe toxicity to normal human cells.

Systematic review of synergistic effect between air pollutants and temperature on human mortality in China / 环境与职业医学

Background Air pollutants and extreme temperature both pose significant threats to human health, but the synergistic effect between air pollutants and temperature on health is inconsistent. Objective To explore a potential synergistic effect between air pollutants and temperature on the mortality in China through literature review. Methods Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure, VIP Information Chinese Journal Service Platform, PubMed, Web of Science, Science Direct, and Embase databases were searched. "Temperature" "air pollution" "mortality" were selected as keywords to collect literature on synergistic effect between air pollutants and temperature on mortality in China. Literature was published from 2000-01-01 to 2022-07-31 in Chinese or English. Two researchers screened the literature independently according to the inclusion criteria, and the results were integrated and analyzed after data extraction. The "meta" package of R software was used for meta-analysis. Results Twenty-seven studies met the inclusion criteria and associated air pollutants included PM10, PM2.5, O3, SO2, NO2, and CO. The impact of PM10 and PM2.5 on mortality in high temperature days was higher than that in moderate temperature days. In high temperature days, a 10 μg·m−3 increment in PM10 concentration corresponded to pooled estimates of 2.30% (95%CI: 1.34%-3.26%), 1.23% (95%CI: 0.64%-1.82%), and 1.42% (95%CI: 0.63%-2.22%) increase in non-accidental, cardiovascular, and respiratory mortalities, respectively. A 10 μg·m−3 increment in PM2.5 concentration corresponded to pooled estimates of 2.56% (95%CI: 2.00%-3.13%), 2.37% (95%CI: 1.64%-3.12%), and 2.14% (95%CI: 1.03%-3.25%) increase in non-accidental, cardiovascular, and respiratory mortalities, respectively. The synergistic effect of SO2 and NO2 on cardiovascular and respiratory mortalities in low temperature days was higher than that in moderate temperature days. Conclusion The synergistic effects of air pollutants and temperature on mortality in low temperature days or in high temperature days are higher than that in moderate temperature days. The health protection related to these pollutants should be strengthened in these days.

Research progress of photothermal therapy and its synergistic therapy in the treatment of hepatocellular carcinoma / 国际生物医学工程杂志

Primary liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death worldwide, and hepatocellular carcinoma is the main type of primary liver cancer. HCC is insidious and asymptomatic at an early stage, and when clinically relevant, the disease is often in the middle to late stages. As a result, most patients miss out on radical treatment at the time of diagnosis, leading to high recurrence and metastasis rates and poor prognosis. At present, there are more and more methods in the treatment of hepatocellular carcinoma. Photothermal therapy, as an emerging cancer treatment, has attracted widespread attention due to its minimally invasive, low-cost, high efficiency, low side effects and strong targeting. Research progress of photothermal therapy and its synergistic therapy in the treatment of hepatocellular carcinoma were reviewed in this paper, aiming to explore new ideas and strategies for the treatment of hepatocellular carcinoma.

Rhizosphere Exudate-mediated Synergistic Harm of Soil Microorganisms to Medicinal Plants in Continuous Cropping / 中国实验方剂学杂志

Continuous cropping obstacle is the bottleneck of medicinal plant cultivation, which seriously affects the quality and yield of medicinal materials. The research on the mechanism of continuous cropping obstacle has evolved from soil physical and chemical properties and allelopathy in the 1970s to the changes of rhizosphere microenvironment and plant response mechanism at present. According to the available studies in this field and our previous research work, we systematically analyzed the mechanism of rhizosphere exudate-mediated microbial community reconstruction in the soil of the medicinal plants in continuous cropping. Specifically, rhizosphere exudates, providing the carbon source and energy for microbial growth, act as inducers or repellents to induce microbial growth or transfer, thereby changing the physicochemical properties (such as acidity) of rhizosphere soil and further altering the structure of rhizosphere microbial community. Further, we comprehensively discussed the ways of synergism between rhizosphere exudates and soil microorganisms in causing harm to the medicinal plants in continuous cropping. That is, rhizosphere exudates mediate the infection of the rhizosphere by pathogenic microorganisms, increase the susceptibility of the nearby plants, inhibit the defense of the host plants, and protect the pathogens to occupy the dominant niche. The synergistic interaction results in the release of more pathogenic factors such as mycotoxins by rhizosphere pathogens, enhanced toxicity of rhizosphere allelochemicals, and deterioration of soil physical and chemical properties. This paper summarizes the role of interaction between rhizosphere exudates and soil microorganisms in the formation of continuous cropping obstacles, aiming to provide a new research idea for revealing the formation mechanism as well as the theoretical support for overcoming continuous cropping obstacles of medicinal plants.