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Objective: To establish a mice model that is more in line with the human immunocompromised state, and to investigate the regulatory effect of Rosa laevigata Michx., probiotics and their combination on their immune function. Methods: Immunosuppressive model of mice was established by using cyclophosphamide with different dosage, time and end point, and compared with immunosuppressive model induced by hydrocortisone and cyclosporine A, immunosuppressive model of mice was established by injecting 25 mg/kg cyclophosphamide 7 times every other day, without recovery period; changes in the proportion of lymphocytes in spleen （CD4+T cells, CD8+T cells, CD19+B cells） were analyzed by flow cytometry; qRT-PCR was used to detect expression levels of inflammatory factors （IL-1β and IL-6） mRNA in spleen. Results: After continuous injection of 80 mg/kg cyclophosphamide for 3 days, the thymus was atrophied, the spleen was significantly swelling, proportion of immune cells CD4+T cells, CD8+T cells and CD19+B cells in spleen were significantly decreased, while mRNA expressions of IL-1β and IL-6 were up-regulated. After 7 injections of 25 mg/kg cyclophosphamide every other day, the thymus and the spleen were significantly atrophied, proportion of CD4+T cells and CD8+T cells in spleen showed an increasing trend, and mRNA expressions of IL-1β and IL-6 were up-regulated; after 1 week or 2 weeks recovery period from cyclophosphamide injection, weight and index of immune organs, proportion of spleen lymphocytes and mRNA expressions of inflammatory cytokines in spleen were significantly reversed; Rosa laevigata Michx. combined with probiotics could significantly reverse the up-regulation of CD4+T cells and inflammatory factor IL-1β caused by cyclophosphamide. Conclusion: In this study, an immunocompromised mice model has been established with 7 injections of 25 mg/kg cyclophosphamide every other day and without recovery period. And a certain positive immunomodulatory effect of the combination of Rosa laevigata Michx. and probiotics has been found. [ABSTRACT FROM AUTHOR]

BACKGROUND: Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE: To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS: C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured. Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay. Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide. The mRNA expression levels of Runx2, alkaline phosphatase, Osteocalcin, osteoprotegerin, and Wnt/β-catenin signaling pathway-related genes Wnt1, Wnt4, Wnt10b, β-catenin, and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen. The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin, DKK1, c-MYC, and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION: (1) There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells. The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L. (2) Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2, alkaline phosphatase, Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium. (3) Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4, β-catenin, c-MYC mRNA and Active β-catenin, c-MYC, and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium. (4) The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice, and psoralen had a restorative effect on it. The best intervention effect was achieved at a concentration of 200 μmol/L psoralen, and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen. [ABSTRACT FROM AUTHOR]

Objective: To investigate the protective effect and mechanism of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) against cyclophosphamide (CTX)-induced renal injury in mice. Methods: Thirty-two male institute of cancer research (ICR) mice were randomly divided into four groups: control (CON), model (MOD), 50 mg/kg mb DHA-PS (50 DHA-PS), and 100 mg/kg mb DHA-PS (100 DHA-PS), with eight mice in each group. The renal injury model was established by intraperitoneal injection of 80 mg/kg mb CTX. Five days later, the mice in the MOD and DHA-PS groups were gavaged for 7 days with an equal volume of physiological saline and DHA-PS, respectively and then sacrificed. Kidney indexes, serum biochemical indicators, the levels of renal oxidative stress and inflammatory factors, histopathological changes, and non-targeted metabolomics of renal tissues were evaluated. Results: Compared with the MOD group, DHA-PS significantly decreased kidney indexes, creatinine, blood urea nitrogen, cystatin C, and kidney injury molecule-1 levels (P < 0.05), increased the activities of antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) (P < 0.05), reduced the content of malondialdehyde (MDA) (P < 0.05), downregulated the expression of pro-inflammatory cytokines including interleukin (IL)-6, IL-1β, tumor necrosis factor-α (P < 0.05), and upregulated the level of the anti-inflammatory cytokine IL-10 (P < 0.05). Staining results showed a significant restoration of kidney tissue structure in the DHA-PS group. Additionally, the results of renal tissue metabolomics indicated that DHA-PS mitigated CTX-induced metabolic disorders in mouse kidneys mainly by affecting glycerophospholipid metabolism, purine metabolism, and their metabolites. Conclusion: DHA-PS can alleviate CTX-induced renal injury in mice through reducing oxidative stress and inflammatory response, and regulating the glycerophospholipid and purine metabolism pathways.

Objective: To compare the regulatory effects of adlay (Coix lachryma-jobi L.) seeds fermented and not fermented by Lactobacillus plantarum NCU137 on immune and intestinal mucosal barrier function in mice induced by cyclophosphamide (CTX). Methods: BALB/c mice were randomly divided into four groups, including normal, CTX-induced model, non-fermented adlay seed (NFC) and fermented adlay seed (FC) treatment. The mice in the normal and CTX groups were orally administrated with 0.2 mL of physiological saline for 10 days, while those in the NFC and FC groups 0.2 mL of non-fermented and fermented adlay seeds for 10 days, respectively. The immunosuppressed mouse model was established by daily intraperitoneal injection of 100 mg/kg of CTX for the last three days of the administration period, while the normal group was intraperitoneally injected with the same volume of normal saline. Spleen index, the number of spleen T lymphocyte subsets, and the levels of cytokines and immunoglobulin were measured, histopathological examination of the small intestine was performed and intestinal mucosal barrier function was detected. Results: Compared with the CTX group, fermented adlay seeds significantly increased the spleen and thymus indexes of immunosuppressed mice, up-regulated the cluster of differentiation (CD) 4+/CD8+ ratio of spleen T lymphocytes, down-regulated the levels of spleen pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), and increased serum immunoglobulin (Ig) M and IgG levels. Moreover, fermented adlay seeds repaired small intestinal mucosal structure and up-regulated the gene expression of occludin and E-cadherin, and the effect was more pronounced than that of non-fermented adlay seeds. Conclusion: Coix lachryma-jobi L. seeds fermented by L. plantarum NCU137 have the potential to regulate immune and intestinal mucosal barrier function, which are expected to be developed into a novel health food with immunomodulatory function.

This study aimed to investigate the effects of the polysaccharide of Atractylodes macrocephala Koidz (PAMK) on cyclophosphamide (CTX)-induced renal injury in mice and its potential underlying mechanisms. One hundred male C57BL/6 mice, aged 42~43 days, were randomly divided into four groups, with five repetitions in each group and five mice in each repetition. The PAMK group and PAMK+CTX group were orally administered 200 mg/kg PAMK once daily, while the control group and CTX group were given an equivalent amount of saline. From days 25~27 of the experiment, the CTX group and PAMK+CTX group were intraperitoneally injected with 100 mg/kg CTX once daily, while the control group and PAMK group were injected with an equivalent amount of saline. On day 35 of the experiment, the kidneys were collected for histological observation, oxidative stress detection, and transcriptome sequencing. The results showed that compared with the CTX group, the renal injury in the PAMK+CTX group was alleviated. The content of malondialdehyde (MDA) in the kidneys was significantly decreased (P

Objective: The effects of Oviductus Ranae (OR) on cyclophosphamide-induced follicular developmental disorders were analyzed from the perspective of transcriptomics, which provided sufficient theoretical and experimental basis for the study of estrogen-like mechanism of OR. Methods: Sixty screened female Wistar rats were randomly divided into control group (C), model group (M), positive group (P), OR low-dose (ORL) and high-dose group (ORH). Except for the control group, all rats were injected with cyclophosphamide intraperitoneally to establish the rat model of follicular development dysfunction. Except for the model group, the other rats were given corresponding drugs by gavage, and the serum sex hormone contents were determined after 14~16 days of continuous gavage. The ovaries and uterus were extracted and weighed for recording and calculating the organ index. One ovary and uterus were stained with HE staining to calculate the number of follicles at all levels and the thickness of the endometrium, while the other ovary was analyzed by transcriptome, and the differentially expressed genes were screened and analyzed by GO and KEGG enrichment analyses. Results: The results showed that the rat follicular development dysfunction model was successfully established. Compared with the rats in the M, the wet weight and index of the uterus of rats in the ORL and ORH significantly increased (P

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Objective To investigate the effect of the Chinese herbal formula Jinghouzengzhi Recipe (JHZZR) on ovarian reserve and apoptotic status in cyclophosphamide-induced ovarian dysfunction mice. Methods Thirty female mice were randomly divided into cyclophosphamide (Cy) group, cyclophosphamide + JHZZR (Cy+JHZZR) group, and blank control group. Serum and ovarian tissues were collected after cervical dislocation. ELISA was used to measure serum levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol (E2). The number of follicles at each stage in ovarian tissues was counted after HE staining. Real-time quantitative PCR was performed to detect the expression level of Caspase3 mRNA in ovarian tissues, and TUNEL assay was used to detect the apoptotic status of granulosa cells. Results Compared with the blank control group, the number of developing follicles in the ovaries of mice in the Cy group and Cy+JHZZR group significantly decreased, while the number of atretic follicles increased. The number of primordial follicles and primary follicles in the Cy+JHZZR group increased compared to the Cy group, while the number of atretic follicles decreased, with statistical significance (P＜0.05). The AMH level in the serum of mice in the Cy+JHZZR group was higher than that in the Cy group [ (6.12±1.66) ng/mL vs. (4.48±1.77) ng/mL, P<0.05], while there was no significant difference in FSH and E2 levels. The relative expression levels of Caspase3 mRNA in the ovarian tissues of mice in the Cy group and Cy+JHZZR group were 5.86±1.33 and 4.45±1.02, respectively, both were higher than those in the blank control group (2.89±1.10, P＜0.01), with statistical significance between the two groups (P＜0.05). The apoptosis index (AI) of the blank control group, Cy group, and Cy+JHZZR group were (8.37±3.17)%, (16.85±5.46)%, and (12.80±3.34)%, respectively. The AI of the Cy group and Cy+JHZZR group were significantly higher than that of the control group, and the AI of the Cy+JHZZR group was lower than that of the Cy group, with statistical significance (P＜0.05). Conclusion JHZZR can improve ovarian reserve and reduce apoptotic status of ovarian cells in cyclophosphamide-induced ovarian dysfunction mice. [ABSTRACT FROM AUTHOR]

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Copyright of Science & Technology of Food Industry is the property of Science & Technology of Food Industry Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To compare similarities and differences in expression changes of cytotoxic T-lymphocyte antigen-4 (CT-LA-4) and programmed death receptor 1 (PD-1) in immunosuppressed rabbits under different moxibustion interventions. Methods: Twenty large-eared white rabbits were randomly divided into normal group, model group, moxa stick moxibustion (MSM) group and herbal cake-partitioned moxibustion (HPM) group, with five rabbits in each group. CTX-induced immunosuppressed models were prepared by intraperitoneal injection for 7 consecutive days. After successful modeling, MSM and HPM were performed on alternate days for 10 treatments. Rabbits were anesthetized after treatment, and serum, liver and spleen were collected. Serum PD-1 and PD-L1 contents were detected by ELISA. PD-1 in liver tissue was detected by immunohistochemistry, and CTLA-4 mRNA in liver and spleen tissues were detected by RT-qPCR. Results: Both HPM and MSM could reduce PD-1 and PD-L1 levels due to immunosuppression, and could effectively suppress elevated levels of CTLA-4 in spleen and PD-1 and CTLA-4 in liver, which were statistically different compared with immunosuppression model group (P<0.05). Pearson correlation test showed that CTLA-4 and PD-1 in liver tissue had significant positive correlation (r=0.780 7, P<0.001). Conclusion: HPM can improve body immune function by regulating multiple immunosuppressive sites. [ABSTRACT FROM AUTHOR]

Copyright of Science & Technology of Food Industry is the property of Science & Technology of Food Industry Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Anticancer chemotherapy with cyclophosphamide (CTX) is accompanied by toxic side effects such as bone marrow suppression and intestinal mucosal injury, which seriously affects the treatment tolerance and prognosis of patients. In recent years, polysaccharides have been used as detoxifying and synergistic adjuncts for antitumor drugs due to their anticancer, anti-inflammatory, and immunoregulatory activities. This paper systematically summarizes polysaccharide purification technologies, elaborates on the detoxification mechanism of polysaccharides on CTX from multiple perspectives such as immunomodulation, antioxidation, intestinal protection, liver and kidney protection, and reproductive system protection, and discusses the synergistic effect of polysaccharides with CTX by directly or indirectly killing tumors. Furthermore, the regulatory pathways of polysaccharides in cancer chemotherapy are summarized from two aspects: toxicity reduction and efficacy enhancement. We hope that this review could provide a reference for research on the mechanism of action of polysaccharides in reducing the toxicity and enhancing the efficacy of CTX, and provide new directions for reducing the toxic side effects of CTX.

In women with reproductive potential, ovarian dysfunction caused by chemotherapy for breast cancer has far-reaching effects. Ovarian insufficiency can manifest as amenorrhea, menstrual disorders, hot flashes and night sweats, impaired fertility in the short term, and increased cardiovascular risk, reduced bone density, cognitive impairment in the long term. The occurrence of ovarian insufficiency due to chemotherapy is closely related to the type of drug, the number of chemotherapy sessions, the dose of chemotherapy, and the age of the patient. There are many drugs for protecting ovarian function, but in clinical practice, gonadotropin-releasing hormone analogues (GnRHa) are still the mainstay. Other ovarian protection drugs generally lack clinical trial data, and their safety and impact on chemotherapy efficacy need further research.

Objective: To systematic study for different chemical components of swim bladder and donkey skin, and their improvement effects on cyclophosphamide-induced anemia mice. Methods: The chemical characterizations, including total protein content, amino acid composition and molecular weight were measured, respectively. Pepsin-soluble collagens were extracted from swim bladder and donkey skin by hydrochloric acid-pepsin method, and analyzed the content, composition and structure. The anemia model was established by intraperitoneal injected with cyclophosphamide at a dosage of 80 mg/kg. The coefficient of visceral organs and the hematological indexes were observed in mice with swim bladder glue (1.52 g/(kg·d)) or donkey skin glue (1.39 g/(kg·d)) by gavage administration per day. Results: The total protein contents of swim bladder and donkey skin reached more than 97%. The molecular weights of swim bladder glue and donkey skin glue ranged from 50 Da to 328 kDa. Swim bladder collagen and donkey skin collagen were both type Ⅰ collagen. While the content of collagen in swim bladder was 6.51 times than that in donkey skin. However the collagen triple helix structures were different. The swim bladder collagen had an α-helix structure, and the donkey skin collagen structure was mainly anti-parallel. After 28 days of administration, both swim bladder glue and donkey skin glue could promote the recovery of hematopoietic function in cyclophosphamide-induced anemia mice, and swim bladder glue exhibited a better effect. Compared with the model, the erythrocyte, hemoglobin, platelet, reticulocyte, spleen and thymus coefficients of the swim bladder glue were significantly improved (P

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Copyright of Acta Edulis Fungi is the property of Acta Edulis Fungi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective 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 í 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 arc 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. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the effect of Eurotium Cristatum fermentation broth mixed with tea polyphenols on the immune indexes of cyclophosphamide immunosuppressive mice. Methods: Immunosuppressive model was established by intraperitoneal injection of cyclophosphamide with 80 mg/kg for 3 days. High, middle and low dose E. Cristatum fermentation broth mixed with tea polyphenols was administrated to immunosuppressive mice intragastrically for 15 days. The blood index, spleen index, macrophage phagocytic index, half hemolysis value, delayed-type hypersensitivity, the content of IL-2 and tumor necrosis factor-α (TNF-α) were measured. Results: E. Cristatum fermentation broth mixed with tea polyphenols significantly increased the number of white blood cells, red blood cells, hemoglobin, serum hemolysin and IL-2 on immunosuppressive mice, enhanced the spleen index and monocyte-phagocytic index, and improved the delayed type hypersensitivity on mice. Conclusion: E. Cristatum fermentation broth mixed with tea polyphenols can enhance immunity on mice.

Objective: To investigate the protective effect of phycocyanin on hepatorenal co-damage in mice caused by cyclophosphamide, and to provide new research ideas for evaluating liver and kidney therapy drugs. Methods: Female BALB/c mice were randomly divided into blank group, model group, positive control group, high dose group, middle dose group and low dose group. The hepatic and kindy injury model of mice were established by intraperitoneal injection of cyclophosphamide (50, 100, 200 mg/kg), then the mice of blank group and model group were fed with normal saline, mice of positive control group were fed levimidazole hydrochloride (40 mg/kg) and the mice of dosage groups were fed different dosage of instant power of phycocyanin. Interleukin-2 (IL-2), tumournecrosis factor-α (TNF-α), immunoglobulin (IgG), superoxide dismutase (SOD), malondialdehyde (MDA) of serum in mice, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level of liver tissue and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), uric acid (UA), urea nitrogenin (BUN) level of kindey tissue in each group mice were determined by reagent kit method. Experimental results showed that compared with the model group, the serum levels of IL-2, TNF-α and MDA in mice in the phycocyanin dose group decreased significantly (P

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Copyright of Journal of Chinese Institute of Food Science & Technology is the property of Journal of Chinese Institute of Food Science & Technology Periodical Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Chinese Institute of Food Science & Technology is the property of Journal of Chinese Institute of Food Science & Technology Periodical Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Food & Machinery is the property of Food & Machinery Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

ObjectiveTo compare and evaluate the improvement degree of spermatogenic dysfunction mice at different recovery periods after cyclophosphamide modeling.MethodsForty-eight male ICR mice aged 4-5 weeks with the body weight of approximately 18-20 g were randomly divided into three control groups and three model groups, with 8 mice in each group. Each mouse of three model groups was intraperitoneally injected with 60 mg/kg cyclophosphamide continuously from the 1st to 7th day of the experiment, while each mouse of three control groups was intraperitoneally injected with the corresponding volume of normal saline. Then these mice were continued to be fed for another 7, 14 and 21 days after cyclophosphamide injection, respectively. A corresponding control group was set for each model group. The mice in each group were sacrificed after blood collection through orbital veins at corresponding time points. Testis, epididymis and seminal vesicle were taken and weighed, and their reproductive organ indexes were calculated. Histopathological changes of testis and epididymis were compared after HE staining.Sperm quality analysis was used to determine sperm-related indexes. Serum reproductive hormone content, testicular oxidative stress level and testicular signature enzyme activity were detected by ELISA and related kits.Results Compared with the control group, on the 7th, 14th and 21st day after cyclophosphamide treatment, the testicular index of mice in the model group decreased significantly (P

The study was to investigate the effect of SeGUP on the immunomodulatory effect of immunosuppressed mice. A total of 96 Kunming mice, half female and half male, were randomly divided into six groups with 16 mice in each group. Mice was given CY to establish an immunocompromised model except the blank group, and 80 mg/g CY was injected intraperitoneally for three consecutive days. On the 4th day, mice in blank group and model group were intraperitoneally injected with 0.3 mL normal saline every day, mice in positive group were intraperitoneally injected with 200 mg/g APS suspension, mice in high-dose, medium-dose and low-dose SeGUP groups were intraperitoneally injected with 100, 200 and 300 mg/g SeGUP suspension for 7 d. The results showed that the body weight of mice in high-dose SeGUP group and medium-dose SeGUP group was extremely higher than that in low-dose SeGUP group (P<0.01). The K and α in high-dose SeGUP group and medium-dose SeGUP group were extremely higher than those in low-dose SeGUP group (P<0.01). The serum IL-2 content of mice in high-dose SeGUP group was extremely higher than that in medium-dose SeGUP group and positive SeGUP group (P<0.01), and the serum IL-2 content of mice in medium-dose SeGUP group and positive SeGup group was extremely higher than that in low-dose Segup group and blank group (P<0.01). The content of TNF-α, IgM, IFN-γ and IgG in serum in high-dose SeGUP groupand medium-dose SeGUP group were extremely higher than those in low-dose SeGUP group (P<0.01). The thymus index in high-dose SeGUP group and medium-dose SeGUP group was extremely higher than that in low-dose SeGUP group (P<0.01). The study indicates that SeGUP can enhance immune function of immunosuppressed mice by down-regulating spleen index, up-regulating body weight, K, α, IL-2, TNF-α, IgM, IFN-γ, IgG, and thymus index, and 200 and 300 mg/g of SeGUP is better. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy of post-cyclophosphamide conditioning regimen transplantation in the prevention of graft-versus-host disease （GVHD） after allogeneic hematopoietic stem cell transplantation （allo-HSCT） for acute leukemia. Methods Twenty-nine cases of acute leukemia patients undergoing allogeneic hematopoietic stem cell transplantation were selected, among whom, 15 patients were treated with post-cyclophosphamide conditioning regimen （observation group） and 14 patients were treated with classic busulfan/cyclophosphamide conditioning regimen （control group). Patients in the observation group received fludarabine 30 mg/（m² ·d） by intravenous infusion from day 3 to day 7 before transplantation, and busulfan injection 0. 8 mg/kg by intravenous infusion （once every 6 hours） from day 3 to day 6 before transplantation, and cyclophosphamide 50 mg/（m² ·d） by intravenous infusion on day 3 and day 4 after transplantation. Patients in the control group received busulfan injection 0. 8 mg/kg by intravenous infusion （once every 6 hours） from day 3 to day 6 before transplantation, and cyclophosphamide 60 mg/（kg·d） by intravenous infusion on day 3 and day 4 before transplantation. The main observation indicators were the incidence of acute and chronic GVHD and transplantation-related complications after transplantation, and the secondary observation indicators were the time required for cell implantation, and the overall survival （OS） and progression-free survival （PFS） of the patients. Results In the observation group, there were 3 cases of acute GVHD and 1 case of chronic GVHD after transplantation, while in the control group, there were 5 cases of acute GVHD after transplantation. There was no statistically significant difference in the incidence of acute and chronic GVHD between the two groups. There were no statistically significant differences in neutrophil and platelet engraftment time and transplantation-related complications between the two groups. The 1-year and 2-year OS rates of the observation group were 93. 33% and 71. 29%, respectively, the 1-year and 2-year PFS rates were 92. 85% and 70. 93%, respectively, and the 1-year and 2-year relapse-free survival rates were 53. 84% and 38. 46%, respectively. The 1-year and 2-year OS rates of the control group were 53. 83% and 38. 46%, respectively, and the observation group had longer OS and PFS rates than the control group （both P<0. 05). Conclusion Post-cyclophosphamide conditioning regimen can effectively prevent GVHD after allogeneic hematopoietic stem cell transplantation in acute leukemia patients, and the prognosis of the patients is better. [ABSTRACT FROM AUTHOR]

Severe aplastic anemia (SAA) is a severe bone marrow failure syndrome caused by multiple causes, which is clinically manifested with severe anemia, infection and bleeding. The complex pathogenesis of SAA has not been fully understood. SAA is characterized with acute onset, severe disease condition and rapid progression. At present, with the in-depth study of SAA and the improvement of diagnosis and treatment, the therapeutic strategy for SAA has been evolved from classical immunosuppressive therapy based on antithymocyte globulin and cyclosporine to the application of thrombopoietin receptor agonist and combined treatment based on allogeneic hematopoietic stem cell transplantation, which may promote the reconstruction of hematopoietic function of SAA patients to varying degree and significantly improve survival and clinical prognosis, becoming the research hotspot of SAA treatment. In this article, new advances in the treatment of SAA at home and abroad were reviewed. [ABSTRACT FROM AUTHOR]

Objective To evaluate the feasibility of secondary transplantation for patients with acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation. Methods Two acute leukemia patients underwent the first haploidentical hematopoietic stem cell transplantation from two donors with thalassemia, and the number of collected CD34+ cells was 2.57×106 /kg and 1.99×106 /kg per donor, respectively. The first haploidentical hematopoietic stem cell transplantation failed. Secondary transplantation was performed from two non-thalassemia donors, and the number of collected CD34+ cells was 4.28×106 /kg and 5.75×106 /kg per donor, respectively. A reducedintensity conditioning regimen consisting of fludarabine (Flu), busulfan (Bu) and antithymocyte globulin (ATG) was adopted for the secondary transplantation. Results For two recipients, the time of secondary transplantation of neutrophil and platelet was +12 d and +10 d, +10 d and +10 d, respectively. Up to the final follow-up (+1 062 d and +265 d after secondary transplantation), the primary diseases of both two recipients have been completely relieved without evident post-transplantation complications. Conclusions Secondary transplantation with reduced-intensity conditioning regimen may successfully treat acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]

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Objective: To explore the effects of Panax ginseng fruit juice concentrate on immune function in immunocompromised mice. Methods: Totally 72 specific pathogen-free (SPF) C57BL/6J male mice were randomly divided into six groups (n = 12): blank, model, and low-, medium- and high-dose Panax ginseng fruit juice concentrate (83, 166, 249 and 332 mg/kg mb). The model and Panax ginseng fruit juice concentrate groups were injected intraperitoneally with 40 mg/kg mb cyclophosphamide on a daily basis for 10 days while the blank group was intraperitoneally injected with the same amount of phosphate buffered saline (PBS). Afterwards, the mice in the Panax ginseng fruit juice concentrate groups were intragastrically administrated with different dosage of Panax ginseng fruit juice concentrate at a volume of 20 mL/kg mb, and those in the blank and model groups were gavaged with the same volume of distilled water for 15 days. Then, body, spleen and thymus mass, white blood cell count, the number of lymphocyte subsets, cytokine expression levels, and nuclear transcription factor expression levels in immune cells were measured. Results: Panax ginseng fruit juice concentrate could improve the spleen mass/index (spleen/body mass ratio) in immunocompromised mice, increase the number of peripheral blood cells and the number of lymphocytes in immune organs, promote the expression of cytokines interleukin (IL)-2, IL-4 and IL-17, inhibit the expression of transforming growth factor (TGF)-β in immunocompromised mice and partially restore the RNA expression of T-box expressed in T cells (T-bet) and forkhead box protein 3 (Foxp3) (P < 0.05), and the effect of Panax ginseng fruit juice concentrate at a dose of 249 mg/kg mb was the most significant. However, Panax ginseng fruit juice concentrate had no significant effect on restoring the body mass or thymus mass of immunocompromised mice. Conclusion: Panax ginseng fruit juice concentrate can enhance immune function in immunocompromised mice.

Objective To establish a stable cyclophosphamide(CTX) induced ovarian insufficiency rat model and to explore the mechanisms. Methods The survival curve of rats after intraperitoneal injection of different dosage of CTX was drawn and the optimal dose was determined. Sex hormone level, estrous cycle and ovarian histological change were further observed. The underlying mechanisms were explored by transcriptome sequencing. Results The mortality rate of medium and high dose in CTX group was high, so low dose CTX was chosen. After CTX exposure, E2 and AMH decreased(both P＜0.05),while FSH increased(P＜0.01). About half of the model rats showed irregular estrous cycles(P＜0.05). The preantral and antral follicles decreased(P＜0.01, P＜0.05), while atresia follicles increased (P＜0.01). Transcriptome sequencing analysis showed that differentially expressed genes (DEGs) between two groups functioned in channel activity and in transmembrane transporter activity. DEGs mainly enriched in neuroactive ligand-receptor interaction pathway, cAMP signal pathway and calcium signaling pathway, axon guidance. According to the protein-protein interaction network of DEGs,we screened out 14 hub genes. Among them, Leptin, Shh,Ntrk2,GRIN2A,CAMK2A,CaSR and Pvalb have been revealed to be closely related to ovarian function. Conclusions A POI rat model induced by CTX was successfully constructed; the neuroactive ligand-receptor interaction pathway, cAMP signal pathway, calcium signaling pathway and axon guidance pathway are enriched pathways. Lep, Shh, Ntrk2, GRIN2A, CAMK2A, CaSR and Pvalb are potentially key genes.

Objective To compare and evaluate the improvement degree of spermatogenic dysfunction mice at different recovery periods after cyclophosphamide modeling. Methods Forty-eight male ICR mice aged 4-5 weeks with the body weight of approximately 18-20 g were randomly divided into three control groups and three model groups, with 8 mice in each group. Each mouse of three model groups was intraperitoneally injected with 60 mg/kg cyclophosphamide continuously from the 1st to 7th day of the experiment, while each mouse of three control groups was intraperitoneally injected with the corresponding volume of normal saline. Then these mice were continued to be fed for another 7, 14 and 21 days after cyclophosphamide injection, respectively. A corresponding control group was set for each model group. The mice in each group were sacrificed after blood collection through orbital veins at corresponding time points. Testis, epididymis and seminal vesicle were taken and weighed, and their reproductive organ indexes were calculated. Histopathological changes of testis and epididymis were compared after HE staining.Sperm quality analysis was used to determine sperm-related indexes. Serum reproductive hormone content, testicular oxidative stress level and testicular signature enzyme activity were detected by ELISA and related kits.Results Compared with the control group, on the 7th, 14th and 21st day after cyclophosphamide treatment, the testicular index of mice in the model group decreased significantly (P<0.01). The epididymis index decreased significantly on the 7th and 14th day, and the seminal vesicle index decreased obviously on the 7th and 21st day (P<0.05). And the histopathological damage of testis and epididymis of the model group gradually alleviated over time. On the 7th and 14th day after cyclophosphamide treatment, the sperm count of the model group declined remarkably (P<0.01), the serum testosterone (T) level reduced (P<0.05), the malonaldehyde (MDA) content of testis increased significantly (P<0.01), the content of reduced glutathione (GSH) and superoxide dismutase (SOD) decreased obviously (P<0.05),the lactic dehydrogenase (LDH) activity of testis reduced obviously (P<0.05), the gamma-glutamyl transpeptidase (γ-GT) activity increased significantly (P<0.05), the latter two of which are important testicular signature enzymes. Therein on the 7th day after cyclophosphamide treatment, the sperm motility decreased significantly (P<0.001), the rate of sperm malformation increased obviously (P<0.05), the serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) increased notably (P<0.01). Nevertheless on the 21st day after cyclophosphamide treatment, the sperm-related indexes, the content of serum reproductive hormone, the level of testicular oxidative stress and the activity of testicular signature enzyme did not change significantly (P＞0.05). Conclusion The reproductive toxicity in mice was more apparent on the 7th day after intraperitoneal injection with 60 mg/kg cyclophosphamide for seven days, at which time the more desirable spermatogenic dysfunction model of mice could be established. However, with the prolongation of the recovery period, the indexes of spermatogenic dysfunction in mice gradually recovered and approached the normal level on the 21st day after cyclophosphamide treatment. [ABSTRACT FROM AUTHOR]

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Objective: To explore the effect of pituitary adenylate cyclase activating polypeptide (PACAP)27 on the cyclophosphamide-induced testicular injury in the rats, and to clarify its possible mechanism. Methods: Sixty SD rats were randomly divided into control group, model group, PACAP27 group and L-carnitine group, with 15 rats in each group. Except control group, the rats in other groups were treated with cyclophosphamide to establish the models and administrited with drugs. On the 3rd day after the administration, the weights of rats and the testis were weighed, and the testis index was calculated；the levels of serum follicle-stimulating hormone(FSH), luteinizing hormone(LH)and testosterone(T)of the rats in various groups were measured by radioimmunoassay, HE staining was used to observe the pathomorphology of testis tissue of the rats in various groups；the activities of superoxide dismutase (SOD), catalase(CAT)and the levels of malondialdehyde(MDA)in testis tissue of the rats in various groups were detected by enzyme linked immunosorbent assay(ELISA)method, TUNEL staining was used to detect the apoptotic rates of testicular tissue of the rats in various groups, and Western blotting method was used to detect the expression levels of mitochondrial apoptosis pathway-related proteins. The testicular tissue mitochondria were extracted, the opening degrees of the mitochondrial permeability transition pore (mPTP) of the rats in various groups were detected with mitochondrionl isolation reagent, and JC-1 fluorescent staining was used to detect the mitochondrial membrane potential. Results: Compared with control group, the body weight, testis weight and testis index of the rats in model group were decreased (P<0. 05), the levels of FSH, LH and T in serum were decreased(P<0. 05), the activities of SOD and CAT in testis tissue were decreased(P<0. 05), the level of MDA was increased(P<0. 05), the testis tissue had obvious pathological damage, and the apoptotic rate was increased(P<0. 05), the expression levels of cytochrome C(Cyt C), B-cell lymphoma-2 associated X protein(Bax), cysteinyl aspartate specific proteinase-3 (caspase-3)and cysteinyl aspartate specific proteinase-9(caspase-9)proteins were increased (P<0. 05), the expression level of B-cell lymphoma-2(Bcl-2) protein was decreased (P<0. 05), the opening degree of mPTP was enhanced (P<0. 05), and the mitochondrial membrane potential was decreased(P<0. 05). Compared with model group, the testis weights and testis indexes of the rats in PACAP27 group and L-carnitine group were increased(P<0. 05), the levels of FSH, LH and T in serum were increased(P<0. 05), the activities of SOD and CAT were increased(P<0. 05), the levels of MDA were decreased(P<0. 05), the pathological damages of testis tissue were improved, the apoptotic rates were decreased(P<0. 05), the expression levels of Cyt C, Bax, caspase-3 and caspase-9 proteins were decreased (P<0. 05), the expression levels of Bcl-2 protein were increased (P<0. 05), the mPTP opening degrees were decreased(P<0. 05), and the mitochondrial membrane potentials were increased (P<0. 05). Conclusion: PACAP27 may alleviate cyclophosphamide-induced testicular injury in the rats by inhibiting mitochondria-dependent apoptosis pathway. [ABSTRACT FROM AUTHOR]

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Objective: To evaluate the efficacy of cyclophosphamide (CYP) at different doses in replicating the symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS) in an animal model, thereby providing an experimental basis for understanding the pathophysiology of IC/BPS and assessing treatment strategies., Methods: Twenty-eight female Sprague-Dawley rats aged seven weeks were divided into four groups: Group a (25 mg/kg CYP), group b (75 mg/kg CYP), group c (125 mg/kg CYP), and group d (a control group). The rats were injected intraperitoneally with either CYP or saline solution. Evaluations included urine spot tests, von Frey filament pain threshold tests, urodynamic examinations, and histological assessments., Results: The study found that the 25 mg/kg CYP dosage significantly outperformed higher doses in simulating bladder dysfunction and inflammatory responses while minimizing the impact on the rats' physiological functions. Specifically, urine spot area, group a showed a significant reduction in urine spot area compared with the control group ( P < 0.05), while groups b and c did not show significant differences. Pain threshold: The von Frey filament test indicated increased visceral pain in group a, aligning closely with IC/BPS patient symptoms, without a significant increase in urination frequency. Urodynamic assessments: Group a exhibited decreased bladder compliance and reduced maximum bladder capacity ( P < 0.05), with no significant differences in baseline bladder pressure and maximum detrusor pressure across all groups. Histological analysis: Hematoxylin-eosin (HE) staining revealed that bladder tissue in group a had moderate inflammatory reactions, whereas groups b and c showed severe inflammation and tissue damage, correlating with the higher doses of CYP. Furthermore, the urine spot tests and von frey filament tests provided quantitative data supporting the model's reliability, urine spot count, group a had an average urine spot count of (15±3) spots, significantly higher than the control group's (5±2) spots ( P < 0.01). Nociceptive score: Group a nociceptive score increased to 0.5±0.1, indicating heightened pain sensitivity compared with the control group 0.10±0.05 ( P < 0.01)., Conclusion: The 25 mg/kg CYP demonstrated significant advantages in simulating the key features of non-ulcerative IC/BPS, summarizing the main aspects of the human condition, including persistent visceral pain and mild inflammatory reactions in bladder tissue. These findings offer substantial experimental support for drug development and treatment research in IC/BPS and provide new insights into the complex patho-physiology of the disease.

Objective: Through animal experiments, To specifically explore the passage of microRNA (miRNA, miR)-10a through F-Box and WD40 domain protein 7 (FBXW7) and E-box zinc finger binding protein 2 (ZEB2) axis regulates the tumor chemotherapy resistance of non-small cell lung cancer hrough animal experiments. Methods: Non-small cell lung cancer model mice (n=42) were randomly equally divided into three groups-model group, miR-10a group and cyclophosphamide group. The model group were given intraperitoneal injection of normal saline 0.2 mL, and the cyclophosphamide group were given cyclophosphamide 20 mg/kg intraperitoneally at 20 mg/kg, the miR-10a group were given hsa-miR-10a mimics 15 mg/kg combined with cyclophosphamide 20 mg/kg intraperitoneally, once daily for 14 d. Results: The tumor volume of the miR-10a group and the cyclophosphamide group were lower on the 7th and 14th day of treatment than the model group, and the miR-10a group were lower than that of the cyclophosphamide group (P<0.05). The tumor mass of miR-10a group and cyclophosphamide group on the 14th and 28th day of treatment were lower than that of the model group, and the tumor inhibition rate were higher than that of the model group, the difference compared between the miR-10a group and cyclophosphamide group were also statistically significant (P<0.05). The apoptosis index of tumor cells in the miR-10a group and the cyclophosphamide group were higher on the 14th and 28th day of treatment than the model group, and the miR-10a group were higher than the cyclophosphamide group (P<0.05). The levels of serum FBXW7 and ZEB2 in the miR-10a group and the cyclophosphamide group were lower on the 14th and 28th day of treatment than the model group, and the miR-10a group were lower than the cyclophosphamide group(P<0.05). The relative expression levels of FBXW7 and ZEB2 mRNA and protein in the miR-10a group and the cyclophosphamide group were lower than the model group on the 14th and 28th day of treatment, and the miR-10a group were lower than the cyclophosphamide group (P<0.05). Conclusion: Overexpression of miR-10a can inhibit the activation of FBXW7-ZEB2 axis in mice with non-small cell lung cancer, and inhibit the expression of serum FBXW7 and ZEB2, thereby promoting tumor cell apoptosis, improving tumor chemotherapy resistance, and promoting tumor volume reduction. [ABSTRACT FROM AUTHOR]

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The mechanism of Baoyuan Decoction on mice with blood deficiency syndrome was investigated by metabonomics based on gas chromatography-mass spectrometer（GC-MS）. Intraperitoneally injected Kunming mice with cyclophosphamide（CTX） to establish a mouse model of blood deficiency syndrome characterized by decreased leukocyte count. Normal control group, model group, positive control group and Baoyuan Decoction low, medium and high dose groups were established for 14 days. Gas chromatography-mass spectrometry was used to analyze the serum of mice in each experimental group. The metabolites of normal control group and model group were classified by principal component analysis（PCA）, in order to find the the content changes of differential metabolites after Baoyuan Decoction acted on blood deficiency syndrome model mice. In the mean time, the blood biochemical indexes were detected and the organ index of mice were calculated in each group. The results show that Baoyuan Decoction could significantly increase the number of leukocytes, repair the damage of thymus and spleen in blood deficiency syndrome mice. The metabolic profile of mice in the therapeutic group approached the blank control group. 10 different metabolites were found in serum related to the immunosuppressive blood deficiency syndrome caused by CTX, mainly involving three metabolic pathways such as linoleic acid metabolism, therefore speculated that the therapeutic effect of Baoyuan Decoction on blood deficiency syndrome may be achieved by regulating fatty acids, [ABSTRACT FROM AUTHOR]

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[Objective] The paper aimed to study t he regulatory effect of Lycium barbarum glycopeptide (LbGp) on the immunosuppression induced by cyclophosphamide (CY) in chicks.[Method] 200 of 7 days Highland layers were selected and divided into 5 groups randomly : blank group (NC), cyclophosphamide grou p (CY) and high dose of LbGp (LbGpH), middle (LbGpM) and l ow dose of (LbGpL ) groups. The layers of NC group were received normal saline intramuscularly, the layers of the other 4 groups were injected intramuscularly with 80 mg/ (kg · d ) CY for 3 days to building immunosuppression modeling. After that, the l ayers of LbGpH, LbGpM and LbGpL grou ps were given 10, 5, 2. 5 mg/ (kg · d ) of LbGp respectively for 7 days. On t he 7, 14, 21, and 28 days after the first administration, 5 chicks were randomly sel ected to determine their body weight, spleen index, peripheral bl ood lymphocyte transformation, and spleen histological analysis.[Result] LbGpH significantly increased the body weight of CY-induced immunosuppressive chicks (P < 0. 05 ), the LbGpM significantly increased the body weight of CY-induced immunosuppressive chicks (P < 0. 01 ) ; The LbGpM significantly increased the spleen index of CY-induced immunosuppressive chicks (P < 0. 05); The LbGpH and LbGpM significantly increased the peripheral blood lymphocyte transformation rate of CY-induced immunosuppressive chicks (P < 0. 01); The histological results of the spleen showed that the number of germinal centers in each LbGp group was significantly higher t han t hat in the CY group on t he 14th and 21th day after t he first administration (P < 0. 05) .[Conclusion] L. barbarum glycopeptide has a significant antagonistic effect on the immunosuppression of chicks induced by cyclophosphamide, and the middle dose group has the best effect. [ABSTRACT FROM AUTHOR]