Enhancing Effects of Ligustrazine on Expression of CD31 and Hematopoietic Reconstitution in Syngenic Bone Marrow Transplantation of Mice

Summary： The effect of ligustrazine on the expression of CD31 in syngenic bone marrow transplantation （BMT） mice was studied. Fifty-six Balb/c mice were divided into 3 groups： normal control group. BMT control group, and ligustrazine treated group. Syngenic BMT mouse models were established according to the literatures. In BMT control group and the ligustrazine treated group, the mice were given respecxively orally 0.2 mL saline and 2 mg ligustrazine twice a day. On the 7th, 14th, and 21st day after BMT, the mice were killed. The expression of CD31 on the surface of bone marrow nuclear cells （BMNC） was detected by flow cytometry. Peripheral blood leukocytes, platelets and BMNC were counted. Histological observation of bone marrow was made. The results showed thai in ligustrazine treated group the peripheral blood leukocylcs, platelets and BMNC counts, and the expression of CD31 on the day 7, 14, 21 after BMT were higher than in BMTcontrol group （P〈0.01 or P〈0.05）. In conclusion, ligustrazine could obviously enhance the CD31 expression on the surface of BMNC after syngcnic BMT in mice, which may be one of the mecha- nisms underlying the ligustrazine accelerating hematopoietic reconstitution in syngenic BMT.

Study on the Effect of Ligustrazine on Hematopoietic Reconstitution in Bone Marrow Transplantation Mice

To explore tile effects of ligustrazine on hematopoietic reconstitution and its mechanism after bone marrow transplantation (BMT), the allogenic BMT mice were given intra-abdominal injection of 2,mg ligustrazine twice a day. On the 1st, 7th, 14th, and 28th day after BMT, peripheral blood cells and bone marrow nuclear cells (BMNC) were counted, and the histological features were evaluated. On the 7th, 14th, 21st day after BMT, CXCR4 expression on the BMNC was assayed. The results showed that peripheral blood cell counts and BMNC counts in ligustrazine-treated group on the 7th, 14th, 28th day were higher than those in BMT group (P<0. 01 or P<O. 05). The percentage of hematopoietic tissue volume, fat tissue hyperplasia and congestion and dilation degree of microvessel in ligustrazine-treated group on the 7th, 14th, 21st, 28th day was higher than those in BMT group. The CXCR4 expression levels in ligustrazine-treated group were higher than in BMT group (P<0.01 or P<0. 05) on the 7th and 14th day, and were lower than in BMT group on the 21st day (P<0. 01 ). It is concluded that the ligustrazine can accelerate hematopoietic reconstruction, enhance growth of hematopoietic tissues and promote the repair of microvessels. The CXCR4 expres- sion levels on BMNC may be responsible for the effect of ligustrazine.

EFFECTS OF INTERLEUKIN-4 ON GRANULOCYTE-MACROPHAGE-COLONY FORMATION FROM MURINE BONE MARROW CELLS AND HEMATOPOIETIC RECONSTITUTION FOLLOWING MURINE ALLOGENEIC BONE MARROW TRANSPLANTATION

We investigated the effects of mouse recombinant IL-4 on hematopoiesis in vitro and in vivo. IL-4 alone was found to be incapable of stimulating colony formation, but it inhibited both IL-3-and GM-CSF-induced colony formation by murine hematopoietic progenitor cells. In contrast, colony formation induced by G-CSF was enhanced in the presence of IL-4. We also studied the influence of IL-4 on hematopoietic reconstiution after allogeneic bone marrow transplantation in a murine medel, and found that IL-4 had significant inhibitory effects on neutrophil recovery and that neutrophil recovery accelerated by IL-3 and G-CSF was significantly suppressed by IL-4. The combination of IL-4 and GM-SF caused a significant decrease in the absolute number of neutrophils.

The related effects of astragalus polysaccharides on the improvement of bone marrow suppression and hematopoietic stem cells during chemotherapy in elderly patients with lung cancer

Objective:To investigate the effects of astragalus polysaccharides(APS)on bone marrow suppression and hematopoietic stem cells during chemotherapy in elderly patients with lung cancer.Methods:120 elderly patients with lung cancer treated in the first hospital of Xingtai city from January 2019 to early December 2019 were divided into the treatment group and the control group by the random number table method,all of whom received pemetrexed+carboplatin chemotherapy,and the treatment group was treated with APS at the same time.The efficacy was evaluated after 2 cycles of chemotherapy,bone marrow suppression was observed,and levels of TCM symptoms score,peripheral blood T lymphocyte subgroup index,L-selectin(CD62L)and macrophage differentiation antigen-1(Mac-1)were measured before and after 2 cycles of chemotherapy.Results:The response rate(RR)was 56.67%in the treatment group and 45.00%in the control group,with no statistically significant difference(P>0.05);The disease control rate(DCR)in the treatment group was 81.67%,which was significantly higher than 65.00%in the control group(P<0.05);The reduction degree of leukopenia in the treatment group was significantly lower than that in the control group(P<0.05);The treatment group had a platelet reduction of grade 1+2 at a rate of 40.00%,and hemoglobin reduction of grade 1+2 at a rate of 28.33%,which were significantly lower than the control group at 65.00%and 58.33%(P<0.05);Compared with those before chemotherapy,the total score of TCM symptoms,serum CD62L and Mac-1 levels in the two groups all decreased significantly after chemotherapy,and they were significantly lower in the treatment group than in the control group(P<0.05);After chemotherapy,CD3+,CD4+and CD4+/CD8+in the treatment group increased significantly and they were all higher in the treatment group than in the control group,while CD8+decreased significantly and was lower in the treatment group than in the control group(P<0.05).There was no statistically significant difference in T lymphocyte subsets before and after chemotherapy in the control group(P>0.05).Conclusion:Astragalus polysaccharide can improve the chemotherapy effect and improve the bone marrow suppression in elderly patients with lung cancer,which may be related to its obvious enhancement of immune function and decrease of CD62L and Mac-1 levels.

Phase 1 human trial of autologous bone marrow-hematopoietic stem cell transplantation in patients with decompensated cirrhosis

AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated cirrhosis were included. Approximately 200 mL of the bone marrow of the patients was aspirated, and CD34+ stem cells were selected. Between 3 to 10 million CD34+ cells were isolated. The cells were slowly infused through the hepatic artery of the patients.RESULTS: Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results. In patient 2 prothrombin time was decreased; however, her total bilirubin, serum creatinine, and Model of End-Stage Liver Disease (MELD) score worsened at the end of follow up. In patient 3 there was improvement in serum albumin, porthrombin time (PT), and MELD score. Patient 4 developed radiocontrast nephropathy after the procedure, and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later. Because of the major side effects seen in the last patient, the trial was prematurely stopped.CONCLUSION: Infusion of CD34+ stem cells through the hepatic artery is not safe in decompensated cirrhosis. Radiocontrast nephropathy and hepatorenal syndrome could be major side effects. However, this study doesnot preclude infusion of CD34+ stem cells through other routes.

Proliferative Functions of Hematopoietic Progeritors in Bone Marrow of Chickens Infected with Cav

Development of marrow colony forming unit erythrocytic (CFU-E), colony forming unit granulocytic and macrophagic (CFU-GM) and colony forming unit fibroblastic (CPU桭) of chicken anemia virus (CAV) infection were examined by using In vitro culture techniques of hematopoietic progenitor cells. Chicks were inoculated intraperitoneally and intramuscularly with CAV at one day of age. The results showed that CAV inhibited proliferation of CFU-E and CFU-GM of chick bone marrow. In vitro culture, growth of CFU-E was inhibited from day 14 to 35 postinoculation (PI), and growth of CFU-GM was greatly inhibited from 7 to 21 days PI. Growth of CFU-E and CFU-GM recovered at day 42 PI. No effect was found on growth of CFU-F of bone marrow in chicks infected CAV.

Hydrogel loaded with bone marrow stromal cell-derived exosomes promotes bone regeneration by inhibiting inflammatory responses and angiogenesis

BACKGROUND Bone healing is a complex process involving early inflammatory immune regu-lation,angiogenesis,osteogenic differentiation,and biomineralization.Fracture repair poses challenges for orthopedic surgeons,necessitating the search for efficient healing methods.AIM To investigate the underlying mechanism by which hydrogel-loaded exosomes derived from bone marrow mesenchymal stem cells(BMSCs)facilitate the process of fracture healing.METHODS Hydrogels and loaded BMSC-derived exosome(BMSC-exo)gels were charac-terized to validate their properties.In vitro evaluations were conducted to assess the impact of hydrogels on various stages of the healing process.Hydrogels could recruit macrophages and inhibit inflammatory responses,enhance of human umbilical vein endothelial cell angiogenesis,and promote the osteogenic differen-tiation of primary cranial osteoblasts.Furthermore,the effect of hydrogel on fracture healing was confirmed using a mouse fracture model.RESULTS The hydrogel effectively attenuated the inflammatory response during the initial repair stage and subsequently facilitated vascular migration,promoted the formation of large vessels,and enabled functional vascularization during bone repair.These effects were further validated in fracture models.CONCLUSION We successfully fabricated a hydrogel loaded with BMSC-exo that modulates macrophage polarization and angiogenesis to influence bone regeneration.

Small extracellular vesicles from hypoxia-preconditioned bone marrow mesenchymal stem cells attenuate spinal cord injury via miR-146a-5p-mediated regulation of macrophage polarization

Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.

Bone marrow-derived mesenchymal stem cell-derived exosomeloaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage

BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.

O-linkedβ-N-acetylglucosaminylation may be a key regulatory factor in promoting osteogenic differentiation of bone marrow mesenchymal stromal cells

Cumulative evidence suggests that O-linkedβ-N-acetylglucosaminylation(OGlcNAcylation)plays an important regulatory role in pathophysiological processes.Although the regulatory mechanisms of O-GlcNAcylation in tumors have been gradually elucidated,the potential mechanisms of O-GlcNAcylation in bone metabolism,particularly,in the osteogenic differentiation of bone marrow mesenchymal stromal cells(BMSCs)remains unexplored.In this study,the literature related to O-GlcNAcylation and BMSC osteogenic differentiation was reviewed,assuming that it could trigger more scholars to focus on research related to OGlcNAcylation and bone metabolism and provide insights into the development of novel therapeutic targets for bone metabolism disorders such as osteoporosis.

Bone marrow mesenchymal stem cells in treatment of peripheral nerve injury

Peripheral nerve injury(PNI)is a common neurological disorder and complete functional recovery is difficult to achieve.In recent years,bone marrow mesenchymal stem cells(BMSCs)have emerged as ideal seed cells for PNI treatment due to their strong differentiation potential and autologous trans-plantation ability.This review aims to summarize the molecular mechanisms by which BMSCs mediate nerve repair in PNI.The key mechanisms discussed include the differentiation of BMSCs into multiple types of nerve cells to promote repair of nerve injury.BMSCs also create a microenvironment suitable for neuronal survival and regeneration through the secretion of neurotrophic factors,extracellular matrix molecules,and adhesion molecules.Additionally,BMSCs release pro-angiogenic factors to promote the formation of new blood vessels.They modulate cytokine expression and regulate macrophage polarization,leading to immunomodulation.Furthermore,BMSCs synthesize and release proteins related to myelin sheath formation and axonal regeneration,thereby promoting neuronal repair and regeneration.Moreover,this review explores methods of applying BMSCs in PNI treatment,including direct cell trans-plantation into the injured neural tissue,implantation of BMSCs into nerve conduits providing support,and the application of genetically modified BMSCs,among others.These findings confirm the potential of BMSCs in treating PNI.However,with the development of this field,it is crucial to address issues related to BMSC therapy,including establishing standards for extracting,identifying,and cultivating BMSCs,as well as selecting application methods for BMSCs in PNI such as direct transplantation,tissue engineering,and genetic engineering.Addressing these issues will help translate current preclinical research results into clinical practice,providing new and effective treatment strategies for patients with PNI.

Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway

BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.

Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

Ecthyma Gangrenosum in Patient with Bone Marrow Aplasia: A Case Report and Review of the Literature

Background: Ecthyma gangrenosum (EG) is an infrequent and discernible cutaneous disease caused by Pseudomonas aeruginosa. In situations where it is associated with septicemia in debilitated patients, the prognosis is usually unfavorable. Objective: In this case, we aim to verify risk factors, clinical, bacteriological and therapeutic characteristics of ecthyma gangrenosum and we review the literature to highlight the features of this rare condition and discuss the role of early diagnosis and treatment. Case Report: We describe the clinical case of a 4-year-old male with bone marrow aplasia who was presented with characteristic skin lesions of EG and developed sepsis later. Conclusion: EG is a cutaneous disease characterized by its aggressive nature. The presence of delayed diagnosis and therapy, along with sepsis, is closely linked to a high mortality rate. Treatment is empirically founded on an aggressive initial approach.

Injectable bone marrow microniches by co-culture of HSPCs with MSCs in 3D microscaffolds promote hematopoietic reconstitution from acute lethal radiation

Hematopoietic syndrome of acute radiation syndrome(h-ARS)is an acute illness resulted from the damage of bone marrow(BM)microenvironment after exposure to radiation.Currently,the clinical management of h-ARS is limited to medication-assisted treatment,while there is still no specific therapy for the hematopoietic injury from high-dose radiation exposure.Our study aimed to assemble biomimetic three-dimensional(3D)BM microniches by co-culture of hematopoietic stem and progenitor cells(HSPCs)and mesenchymal stem cells(MSCs)in porous,injectable and viscoelastic microscaffolds in vitro.The biodegradable BM microniches were then transplanted in vivo into the BM cavity for the treatment of h-ARS.We demonstrated that the maintenance of HSPCs was prolonged by co-culture with MSCs in the porous 3D microscaffolds with 84μm in pore diameter and 11.2 kPa in Young’s modulus compared with 2D co-culture system.Besides,the minimal effective dose and therapeutic effects of the BM microniches were investigated on a murine model of h-ARS,which showed that the intramedullary cavity-injected BM microniches could adequately promote hematopoietic reconstitution and mitigate death from acute lethal radiation with a dose as low as 1000 HSPCs.Furthermore,the mRNA expression of Notch1 and its downstream target gene Hes1 of HSPCs were increased when co-cultured with MSCs,while the Jagged1 expression of the co-cultured MSCs was upregulated,indicating the significance of Notch signaling pathway in maintenance of HSPCs.Collectively,our findings provide evidence that biomimetic and injectable 3D BM microniches could maintain HSPCs,promote hematopoiesis regeneration and alleviate post-radiation injury,which provides a promising approach to renovate conventional HSPCs transplantation for clinical treatment of blood and immune disorders.

Preliminary delivery efficiency prediction of nanotherapeutics into crucial cell populations in bone marrow niche

Several crucial stromal cell populations regulate hematopoiesis and malignant diseases in bone marrow niches.Precise regulation of these cell types can remodel niches and develop new therapeutics.Multiple nanocarriers have been developed to transport drugs into the bone marrow selectively.However,the delivery efficiency of these nanotherapeutics into crucial niche cells is still unknown,and there is no method available for predicting delivery efficiency in these cell types.Here,we constructed a three-dimensional bone marrow niche composed of three crucial cell populations:endothelial cells(ECs),mesenchymal stromal cells(MSCs),and osteoblasts(OBs).Mimetic niches were used to detect the cellular uptake of three typical drug nanocarriers into ECs/MSCs/OBs in vitro.Less than 5%of nanocarriers were taken up by three stromal cell types,and most of themwere located in the extracellular matrix.Delivery efficiency in sinusoidal ECs,arteriole ECs,MSCs,and OBs in vivo was analyzed.The correlation analysis showed that the cellular uptake of three nanocarriers in crucial cell types in vitro is positively linear correlated with its delivery efficiency in vivo.The delivery efficiency into MSCs was remarkably higher than that into ECs and OBs,no matterwhat kind of nanocarrier.The overall efficiency into sinusoidal ECswas greatly lower than that into arteriole ECs.All nanocarriers were hard to be delivered into OBs(<1%).Our findings revealed that cell tropisms of nanocarriers with different compositions and ligand attachments in vivo could be predicted via detecting their cellular uptake in bone marrow niches in vitro.This study provided the methodology for niche-directed nanotherapeutics development.

Diagnostic Efficacy of^(18)F-FDG PET/CT in Detecting Bone Marrow Infiltration in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma

Objective Diffuse large B-cell lymphoma(DLBCL)is often associated with bone marrow infiltration,and 2-deoxy-2-(18F)fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT)has potential diagnostic significance for bone marrow infiltration in DLBCL.Methods A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included.Bone marrow biopsy and^(18)F-FDG PET/CT examinations were performed at the time of initial diagnosis.Kappa tests were used to evaluate the agreement of^(18)F-FDG PET/CT with the gold standard,and the imaging features of DLBCL bone marrow infiltration on PET/CT were described.Results The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy(P=0.302)or between the two bone marrow biopsies(P=0.826).The sensitivity,specificity,and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923(95%CI,0.759-0.979),0.934(95%CI,0.855-0.972),and 0.857,respectively.Conclusion^(18)F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration.PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.

Treatment of postherpetic neuralgia by bone marrow aspirate injection:A case report

BACKGROUND Postherpetic neuralgia(PHN)is the most frequent and a difficult-to-treat complication of herpes zoster(HZ).Its symptoms include allodynia,hyperalgesia,burning,and an electric shock-like sensation stemming from the hyperexcitability of damaged neurons and varicella-zoster virus-mediated inflammatory tissue damage.HZ-related PHN has an incidence of 5%–30%,and in some patients,the pain is intolerable and can lead to insomnia or depression.In many cases,the pain is resistant to pain-relieving drugs,necessitating radical therapy.CASE SUMMARY We present the case of a patient with PHN whose pain was not cured by conventional treatments,such as analgesics,block injections,or Chinese medicines,but by bone marrow aspirate concentrate(BMAC)injection containing bone marrow mesenchymal stem cells.BMAC has already been used for joint pains.However,this is the first report on its use for PHN treatment.CONCLUSION This report reveals that bone marrow extract can be a radical therapy for PHN.

Effect of ginsenoside Rg1 on hematopoietic stem cells in treating aplastic anemia in mice via MAPK pathway

BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at play.METHODS We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 d.The invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin staining.Moreover,orbital blood of mice was collected for blood routine examinations.Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice.Additionally,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot.RESULTS Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of AA.Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice.In comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX.Furthermore,it helped alleviate the blockade in the cell cycle.Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.CONCLUSION This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.

Exosomes from bone marrow mesenchymal stem cells are a potential treatment for ischemic stroke

Exosomes derived from human bone marrow mesenchymal stem cells(MSC-Exo)are characterized by easy expansion and storage,low risk of tumor formation,low immunogenicity,and anti-inflammatory effects.The therapeutic effects of MSC-Exo on ischemic stroke have been widely explored.However,the underlying mechanism remains unclear.In this study,we established a mouse model of ischemic brain injury induced by occlusion of the middle cerebral artery using the thread bolt method and injected MSC-Exo into the tail vein.We found that administration of MSC-Exo reduced the volume of cerebral infarction in the ischemic brain injury mouse model,increased the levels of interleukin-33(IL-33)and suppression of tumorigenicity 2 receptor(ST2)in the penumbra of cerebral infarction,and improved neurological function.In vitro results showed that astrocyte-conditioned medium of cells deprived of both oxygen and glucose,to simulate ischemia conditions,combined with MSC-Exo increased the survival rate of primary cortical neurons.However,after transfection by IL-33 siRNA or ST2 siRNA,the survival rate of primary cortical neurons was markedly decreased.These results indicated that MSC-Exo inhibited neuronal death induced by oxygen and glucose deprivation through the IL-33/ST2 signaling pathway in astrocytes.These findings suggest that MSC-Exo may reduce ischemia-induced brain injury through regulating the IL-33/ST2 signaling pathway.Therefore,MSC-Exo may be a potential therapeutic method for ischemic stroke.