Local Peripheral Effects of <i>β</i>-Caryophyllene through CB₂Receptors in Neuropathic Pain in Mice

β-Caryophyllene (BCP) is known as a common constitute of the essential oils of numerous food plants and primary component in Cannabis. In this study, we investigated the effect of local intraplantar (i.pl.) injection of BCP on mechanical hypersensitivity induced by partial sciatic nerve ligation (PSNL) in mice. Relative to sham operation controls, mice with the PSNL displayed a maximum level of hyperresponsiveness to von Frey metallic filament on post-operative day 7. PSNL-induced allodynia was seen in the ipsilateral side of nerve ligation, but not in the contralateral side. The i.pl. injection of BCP into the ipsilateral hindpaw to PSNL attenuated mechanical allodynia in a dose-dependent manner. BCP injection into the contralateral hindpaw did not produce anti-allodynic effects, suggesting a local peripheral anti-allodynic effect of BCP. Anti-allodynic effects induced by i.pl. injection of BCP were prevented by pretreatment with the cannabinoid (CB2) receptor antagonist AM630, but not by the CB1 receptor antagonist AM251. These data suggest that i.pl. injection of BCP could produce anti-allodynia by activating peripheral CB2 receptors, but not CB1 receptors in a mouse model of neuropathic pain. Taken together, these results suggest that peripheral CB2 receptors may contribute to the effectiveness of BCP in the treatment of neuropathic pain disorders.

C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

P2Y1 receptor in Alzheimer’s disease

Alzheimer’s disease is the most frequent form of dementia characterized by the deposition of amyloid-beta plaques and neurofibrillary tangles consisting of hyperphosphorylated tau.Targeting amyloid-beta plaques has been a primary direction for developing Alzheimer’s disease treatments in the last decades.However,existing drugs targeting amyloid-beta plaques have not fully yielded the expected results in the clinic,necessitating the exploration of alternative therapeutic strategies.Increasing evidence unravels that astrocyte morphology and function alter in the brain of Alzheimer’s disease patients,with dysregulated astrocytic purinergic receptors,particularly the P2Y1 receptor,all of which constitute the pathophysiology of Alzheimer’s disease.These receptors are not only crucial for maintaining normal astrocyte function but are also highly implicated in neuroinflammation in Alzheimer’s disease.This review delves into recent insights into the association between P2Y1 receptor and Alzheimer’s disease to underscore the potential neuroprotective role of P2Y1 receptor in Alzheimer’s disease by mitigating neuroinflammation,thus offering promising avenues for developing drugs for Alzheimer’s disease and potentially contributing to the development of more effective treatments.

Runx2 regulates peripheral nerve regeneration to promote Schwann cell migration and re-myelination

Runx2 is a major regulator of osteoblast differentiation and function;however,the role of Runx2 in peripheral nerve repair is unclea r.Here,we analyzed Runx2expression following injury and found that it was specifically up-regulated in Schwann cells.Furthermore,using Schwann cell-specific Runx2 knocko ut mice,we studied peripheral nerve development and regeneration and found that multiple steps in the regeneration process following sciatic nerve injury were Runx2-dependent.Changes observed in Runx2 knoc kout mice include increased prolife ration of Schwann cells,impaired Schwann cell migration and axonal regrowth,reduced re-myelination of axo ns,and a block in macrophage clearance in the late stage of regeneration.Taken together,our findings indicate that Runx2 is a key regulator of Schwann cell plasticity,and therefore peripheral nerve repair.Thus,our study shows that Runx2 plays a major role in Schwann cell migration,re-myelination,and peripheral nerve functional recovery following injury.

Role of triggering receptor expressed on myeloid cells 1/2 in secondary injury after cerebral hemorrhage

Intracerebral hemorrhage(ICH)is a common severe emergency in neurosurgery,causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically,especially among patients with poor functional outcomes.ICH is often accompanied by decreased consciousness and limb dysfunction.This seriously affects patients’ability to live independently.Although rapid advances in neurosurgery have greatly improved patient survival,there remains insufficient evidence that surgical treatment significantly improves long-term outcomes.With in-depth pathophysiological studies after ICH,increasing evidence has shown that secondary injury after ICH is related to long-term prognosis and that the key to secondary injury is various immune-mediated neuroinflammatory reactions after ICH.In basic and clinical studies of various systemic inflammatory diseases,triggering receptor expressed on myeloid cells 1/2(TREM-1/2),and the TREM receptor family is closely related to the inflammatory response.Various inflammatory diseases can be upregulated and downregulated through receptor intervention.How the TREM receptor functions after ICH,the types of results from intervention,and whether the outcomes can improve secondary brain injury and the long-term prognosis of patients are unknown.An analysis of relevant research results from basic and clinical trials revealed that the inhibition of TREM-1 and the activation of TREM-2 can alleviate the neuroinflammatory immune response,significantly improve the long-term prognosis of neurological function in patients with cerebral hemorrhage,and thus improve the ability of patients to live independently.

N-acetylcysteine and zinc sulphate abate di-2-ethylhexyl phthalate-mediated reproductive dysfunction in rats:Focus on oxidative and sex hormone receptors mechanisms

Objective:To investigate the potential of N-acetylcysteine(NAC)and zinc sulphate(ZnSO_(4))in mitigating reproductive dysfunction caused by di-2-ethylhexyl phthalate(DEHP)in rats and to understand the underlying mechanisms,specifically oxidative stress and sex hormone receptor activity.Methods:Thirty-five male Wistar rats were randomly divided into five equal groups(n=7 per group).Group 1 was administered 0.5 mL of distilled water and served as the control group.Group 2 was given only DEHP(750 mg/kg/day),while group 3,4 and 5 were given DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day),DEHP(750 mg/kg/day)plus ZnSO_(4)(0.5 mg/kg/day),and DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day)as well as ZnSO_(4)(0.5 mg/kg/day),respectively.All treatments lasted for 21 days.Samples were obtained after the rats were sacrificed,and hormones levels in the serum and markers of oxidative stress in the testicles were analyzed using the enzyme-linked immunosorbent assay.The amount of androgen receptors in the testicles was determined by immunohistochemistry,and the susceptibility of testosterone and DEHP to bind to androgen receptor and 5α-reductase was determined by molecular docking studies.Results:DEHP decreased reproductive hormones,testicular antioxidant enzymes,increased malondialdehyde levels,and negatively impacted histology of the pituitary and testes.NAC or ZnSO_(4) treatment showed a marked improvement in testicular antioxidant status and hormone levels,as well as a positive effect on the histology of the pituitary and testes.The combination of both treatments appeared to be more effective.The affinity of DEHP to bind to androgen receptors may lead to disruption of androgen receptor signaling,which can further result in dysfunction of hormones related to androgen.However,NAC is more likely to form stronger binding interactions with follicle stimulating hormone and luteinizing hormone receptors,as well as gonadotropin-releasing hormone receptors,when compared to DEHP.Conclusions:The possibility that NAC and ZnSO_(4) could downregulate DEHP-induced sex hormone changes is suggested by their potential to reduce toxicity.

Toll-like receptors 2 polymorphism is associated with psoriasis: A case-control study in the northern Chinese population

Background:Psoriasis is a disease caused by genetics and immune system dysfunction,affecting the skin and joints.Toll-like receptors(TLRs)play an important role in triggering the innate immune response and controlling adaptive immunity.The role of TLR2 in the progression of psoriasis is not well understood.Methods:A case-control study was conducted on a northern Chinese Han population,consisting of psoriasis patients and healthy control subjects.Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction(ARMS-PCR),and allele and genotype frequencies of four SNPs in TLR2 were analyzed in 270 psoriasis patients and 246 healthy controls.Results:Four TLR2 SNPs(rs11938228,rs4696480,rs3804099,rs5743699)were genotyped and found to be in linkage disequilibrium.The genotype distributions of rs11938228 and rs4696480 in two groups were in Hardy-Weinberg equilibrium and statistically significant except for the overdominance model.The haplotypes ATTC and ATCC were found to be protective against psoriasis.Conclusion:Our study found a correlation between TLR2 genetic variations and the likelihood of psoriasis in northern China.

Evaluation of left ventricular systolic function in type 2 diabetes mellitus patients with and without peripheral vascular disease

BACKGROUND Peripheral vascular disease(PVD)is a common complication of type 2 diabetes mellitus(T2DM).Patients with T2DM have twice the risk of PVD as nondiabetic patients.AIM To evaluate left ventricular(LV)systolic function by layer-specific global longitudinal strain(GLS)and peak strain dispersion(PSD)in T2DM patients with and without PVD.METHODS Sixty-five T2DM patients without PVD,57 T2DM patients with PVD and 63 normal controls were enrolled in the study.Layer-specific GLS[GLS of the epimyocardium(GLSepi),GLS of the middle myocardium(GLSmid)and GLS of the endocardium(GLSendo)]and PSD were calculated.Receiver operating characteristic(ROC)analysis was performed to calculate the sensitivity and specificity of LV systolic dysfunction in T2DM patients with PVD.We calculated Pearson’s correlation coefficients between biochemical data,echocardiographic characteristics,and layer-specific GLS and PSD.RESULTS There were significant differences in GLSepi,GLSmid and GLSendo between normal controls,T2DM patients without PVD and T2DM patients with PVD(P<0.001).Trend tests revealed a ranking of normal controls>T2DM patients without PVD>T2DM patients with PVD in the absolute value of GLS(P<0.001).PSD differed significantly between the three groups,and the trend ranking was as follows:normal controls<T2DM patients without PVD<T2DM patients with PVD(P<0.001).ROC analysis revealed that the combination of layer-specific GLS and PSD had high diagnostic efficiency for detecting LV systolic dysfunction in T2DM patients with PVD.Lowdensity lipoprotein cholesterol was positively correlated with GLSepi,GLSmid and PSD(P<0.05),while LV ejection fraction was negatively correlated with GLSepi,GLSmid and GLSendo in T2DM patients with PVD(P<0.01).CONCLUSION PVD may aggravate the deterioration of LV systolic dysfunction in T2DM patients.Layer-specific GLS and PSD can be used to detect LV systolic dysfunction accurately and conveniently in T2DM patients with or without PVD.

Glutamate receptors and glutamatergic signalling in the peripheral nerves

In the peripheral nervous system,the vast majority of axons are accommodated within the fibre bundles that constitute the peripheral nerves.Axons within the nerves are in close contact with myelinating glia,the Schwann cells that are ideally placed to respond to,and possibly shape,axonal activity.The mechanisms of intercellular communication in the peripheral nerves may involve direct contact between the cells,as well as signalling via diffusible substances.Neurotransmitter glutamate has been proposed as a candidate extracellular molecule mediating the cross-talk between cells in the peripheral nerves.Two types of experimental findings support this idea:first,glutamate has been detected in the nerves and can be released upon electrical or chemical stimulation of the nerves;second,axons and Schwann cells in the peripheral nerves express glutamate receptors.Yet,the studies providing direct experimental evidence that intercellular glutamatergic signalling takes place in the peripheral nerves during physiological or pathological conditions are largely missing.Remarkably,in the central nervous system,axons and myelinating glia are involved in glutamatergic signalling.This signalling occurs via different mechanisms,the most intriguing of which is fast synaptic communication between axons and oligodendrocyte precursor cells.Glutamate receptors and/or synaptic axon-glia signalling are involved in regulation of proliferation,migration,and differentiation of oligodendrocyte precursor cells,survival of oligodendrocytes,and re-myelination of axons after damage.Does synaptic signalling exist between axons and Schwann cells in the peripheral nerves?What is the functional role of glutamate receptors in the peripheral nerves?Is activation of glutamate receptors in the nerves beneficial or harmful during diseases?In this review,we summarise the limited information regarding glutamate release and glutamate receptors in the peripheral nerves and speculate about possible mechanisms of glutamatergic signalling in the nerves.We highlight the necessity of further research on this topic because it should help to understand the mechanisms of peripheral nervous system development and nerve regeneration during diseases.

mRNA Expression of Chemokine Receptors on Peripheral Blood Mononuclear Cells and Correlation with Clinical Features in Systemic Lupus Erythematosus Patients

Objective To investigate the expressions of chemokine receptors and interleukin （IL） receptors on the peripheral blood mononuclear cells （PBMCs） from systemic lupus erythematosus （SLE） patients and their correlations with clinical features as well as SLE disease activity index （SLEDAI）. Methods The mRNA expressions of chemokine receptors and IL receptors on PBMCs of 93 SLE patients and 30 healthy controls were detected by reverse transcription-polymerase chain reaction, including CCR2, CCR3, CCR4, CCR5, CCR6, CCR8, CXCR3, CXCR5, CX3CR1, XCR1, IL-4R, and IL-10R. The clinical features of SLE patients were recorded. The correlations of chemokine receptors and IL receptors mRNA expressions with clinical features as well as SLEDAI were assayed using linear regression analysis. Results The level of CCR5 mRNA in SLE patients （including active and inactive SLE） was signifi- cantly higher than that in healthy controls （P〈0.05）, and there was no significant difference between active and inactive patients in this respect （P〉0.05）. CX3CR1 mRNA expression significantly increased from healthy control to inactive SLE to active SLE in sequence. The others （except for CCR8, CXCR3, and IL-1 OR） in active SLE patients weresignificantly higher than those in both inactive SLE patients and healthy controls （all P〈0.05）. There were positive correlations between SLEDAI and CCR2 （r=0.424, t=4.313, P〈0.001）, CCR3 （r=0.518, t=5.410, P〈0.001）, CCR4 （r=0.376, t=3.851, P〈0.001）, CCR6 （r=0.457, t=4.513,P〈0.001）, CXCR5 （r=0.455, t=4.629, P〈0.001）, CX3CR1 （r=0.44-5, t=4.523, P〈0.001）, as well as XCRI （r=0.540, t=5.445, P〈0.001）. And CCR5 mRNA expression level was positively correlated with IL-4R mRNA （r=0.313, t=2.353, P〈0.05）. The patients with myositis and cutaneous vasculitis simultaneously showed lower levels of CCR5 and CX3CRI, and CCR5 expression was negatively correlated with the scores of SLEDAI in SLE cases accompanied by photosensitivity （r=0.426, t=- 2.155, P〈0.05）. Conclusion Increased expressions of CCR5 and CX3CRI on PBMCs may be indicators in clinical survey for SLE.

Low-dose morphine elicits ventilatory excitant and depressant responses in conscious rats: Role of peripheral <i>µ</i>-opioid receptors

The systemic administration of morphine affects ventilation via a mixture of central and peripheral actions. The aims of this study were to characterize the ventilatory responses elicited by a low dose of morphine in conscious rats;to determine whether tolerance develops to these responses;and to determine the potential roles of peripheral μ-opioid receptors (μ-ORs) in these responses. Ventilatory parameters were monitored via unrestrained whole-body plethysmography. Conscious male Sprague-Dawley rats received an intravenous injection of vehicle or the peripherally-restricted μ-OR antagonist, naloxone methiodide (NLXmi), and then three successive injections of morphine (1 mg/kg) given 30 min apart. The first injection of morphine in vehicle-treated rats elicited an array of ventilatory excitant (i.e., increases in frequency of breathing, minute volume, respiratory drive, peak inspiratory and expiratory flows, accompanied by decreases in inspiratory time and end inspiratory pause) and inhibitory (i.e., a decrease in tidal volume and an increase in expiratory time) responses. Subsequent injections of morphine elicited progressively and substantially smaller responses. The pattern of ventilatory responses elicited by the first injection of morphine was substantially affected by pretreatment with NLXmi whereas NLXmi minimally affected the development of tolerance to these responses. Low-dose morphine elicits an array of ventilatory excitant and depressant effects in conscious rats that are subject to the development of tolerance. Many of these initial actions of morphine appear to involve activation of peripheral μ-ORs whereas the development of tolerance to these responses does not.

Synthesis and Evaluation of 8-[^(131)I]Iodo-substituted Imidazopyridine Derivative as Single Photon Emission Computed Tomography Tracer for Peripheral Benzodiazepine Receptors

A novel N-methyl, N-phenyl-[6-chloro-2-（4-chlorophenyl）-8-iodoimidazo[1, 2-a]- pyridine-3-yl]acetamide （compound Ⅴ） was synthesized, radiolabelled with 131I and evaluated in vitro. In vitro cell uptake studies showed that MDA-MB-231 cells yield four-fold higher specific uptake of [^131I]-compound Ⅵ than MCF-7 cells, corresponding to the increased expression of PBR in MDA-MB-231 cells. Blocking studies significantly reduced the MDA-MB-231 cells uptake of [^131I]-compound Ⅵ. It indicated that [^131I]-compound Ⅵ might be a potential SPECT radioligand for imaging of PBR.

Study of a Quantitative Fluorescence Method for Interleukin 2 Receptor of Mononuclear Cell in Normal Human Peripheral Blood

A quantitative method using fluorescence spectro-photometer to detect theinterleukin 2 reocptor （IL 2R） on the surface of mononuclear cells in normal humanperipheral blood is described. For expression of IL 2R, the optimum conoentration of PHA andCon A were 100 μg/ml and 10 μg/ml respectively. The PHA induced effect on mononuclear cellswas better than Con A induced one. The peak value of IL 2R cxpression was at the 24th h afterstimulation The optimum dilution of the first antibody （anti-Tac） was 1: 50, while the dilution ofthe second antibody（fluorescein conjugated rabbit anti-mousc IgG） was 1: 32 Their optimumincubation period was 20 and 10 min repectively. The concentration of fluorcscein-conjugatedantibody per 1×106 mononuclear cells from the same normal human peripheral blood was5.22±0.45×10-10 mol, and the coefficient of variation was 8. 6%. The concentration offluorescein-conjugated antibody per 1×106PBMC from five healthy individuals was 4. 8±0. 97×10-10 mol Therefore this assay system is stable and quite reproducible.

Effects of Peripherally Acting Opioid Ligands on Central Opioid Receptors and <i>β</i>-Endorphin Release in Stressed Rats

Using the radioreceptor binding assay, μ-opioid receptor (MOR) affinity in the midbrain of stressed rats was higher than in naive controls. MOR density in the rat frontal cortex was reduced after stress. Intragastric administration of the MOR antagonist naloxone methiodide was followed by an increase in the number of MORs in the frontal cortex. However, the MOR agonist loperamide significantly decreased the density of MORs in the frontal cortex and midbrain of naive animals. Loperamide and naloxone methiodide were shown to prevent an increase in MOR affinity and a decrease in MOR density in the midbrain of rats after restraint stress. The restraint stress was accompanied by an increase in the release of β-endorphin (BE) in the ventral tegmental area (VTA) of control rats. After administration, loperamide slightly decreased the release of BE, naloxone methiodide significantly increased the release of BE in the cingulate cortex (CC) of untreated animals, while drugs had no effect on the release of BE in the VTA. The drugs significantly increased the extracellular level of BE in the CC of stressed animals. Loperamide abolished the increase in the stress-induced release of BE in the VTA. By contrast, naloxone methiodide significantly increased the release of BE in the VTA of stressed rats. Our data indicated that activation of peripheral MORs induces depression of the central part of the μ-opioid system, but suppression of peripheral MOR activity induces activation of the central μ-opioid system, the interaction of which can be modulated by stress.

Soluble Interleukin 2 Receptor-Alpha (sIL-2Rα) in the Peripheral Blood of Dogs—Comparison of Malignant Neoplasia with Other Diseases

Background: Cytokines are mediators of diseases. Expression levels in the blood could be of clinical relevance. Objective: sIL-2Rα is used as a marker for different malignancies in human medicine. The aim of this study was to show if sIL-2Rα is detectable and if there is any correlation to different diseases in dogs. Methods: For this purposes sIL-2Rα concentrations in the blood were measured in healthy dogs, in dogs with different non-neoplastic diseases and benign tumors and in dogs with malignant tumors. Serum levels of sIL-2Rα were measured by using a human specific enzyme linked immunosorbent assay (ELISA). Results: Measurement of sIL-2Rα was successful in most of the samples. Dogs with diseases have significantly increased serum levels of sIL-2Rα compared to healthy controls. sIL-2Rα serum levels are higher in patients with non-neoplastic diseases and benign tumors than in those with malignant neoplasia. There is a strong correlation between sIL-2Rα and leukocyte count. Conclusion: Measurements of sIL-2Rα in serum may be helpful in detecting stages and grades of inflammation in the progression of disease. sIL-2Rα could actually not be used as an indicator for malignant diseases in dogs like in humans. The strong correlation between sIL-2Rα and the leukocyte count indicates the inflammatory response to the disease. This could be helpful in giving a prognosis in some cases, because the inflammatory reaction is of prognostic relevance in different diseases including malignant and non-malignant neoplasia. Although the results of our research studies were very promising, further studies should be performed with a canine ELISA.

Expression and significance of toll-like receptor 2,4 in peripheral blood mononuclear cells in patients with systemic inflammatory response syndrome

To explore changes of toll-like receptor (TLR) 2,4 in peripheral blood mononuclear cells (PBMC) in acute abdomen patients with systemic inflammatory response syndrome (SIRS) and their significance.Methods A clinical study was done on 103 patients of which 65 were with SIRS.The mRNA expression of TLR2,4 were detected by RT-PCR;the expression of TNF-α and IL-6 were observed by ELISA;the correlation between TLR2,4 mRNA,the level of TNF-α and IL-6,and the clinical course was evaluated.Results TLR2 mRNA ,TNF-α and IL-6 were upregulated markedly on the first day of hospitalization,then decreased gradually;TLR2 mRNA maintained on high level till the 5th day.The expression of TLR2,4 mRNA was positive correlated with the level of TNF-α and IL-6,and the length of stay.TLR2,4 mRNA expression increased in patients with multiple organ failure.Conclusion In actue abdomen patients with SIRS,the expression of TLR2,4 of PBMC increased markedly,indicating its improtant role in the pathogenesis of SIRS.4 refs,2 figs,2 tabs.

lncRNA-BBOX1-2通过调控成纤维细胞生长因子受体1促进胃癌的发生和发展

目的探讨长链非编码RNA(long non-coding RNA,lncRNA)BBOX1-2通过调控成纤维细胞生长因子受体1(fibroblast growth factor receptor 1,FGFR1)对胃癌的发生发展机制的影响。方法回顾性选取2017年4月至2019年1月于上海交通大学医学院附属瑞金医院卢湾分院接受胃癌根治术30例病人肿瘤组织及癌旁相应正常组织作为研究对象,采用实时定量PCT(real-time PCR,RT-PCR)检测lncRNA-BBOX1-2和FGFR1表达;si-linc-BBOX1-2转染SGC-7901细胞后,通过蛋白质印迹法/细胞存活率分析(MTT)、细胞迁移和侵袭(Transwell)实验、细胞划痕、平板克隆一系列生物学功能实验,检测肿瘤细胞生物学功能及FGFR1表达的变化。结果胃癌组织中的lncRNA-BBOX1-2(3.68±0.58比1.15±0.11)和FGFR1(4.26±0.71比1.19±0.18)表达显著高于癌旁正常组织(P<0.05);si-linc-BBOX1-2转染SGC-7901细胞后,FGFR1表达下调,细胞活力、迁移、侵袭和生存能力明显下降。结论LincRNA-BBOX1-2可通过调控FGFR1的表达介导胃癌细胞的增殖、凋亡、迁移和侵袭,可能为胃癌的治疗提供了新的靶点和潜在的生物学标志物。

Augmentative effect of tetrandrine on pentobarbital hypnosis mediated by 5-HT_(1A) and 5-HT_(2A/2C) receptors in mice

It has been reported that augmentative effect of tetrandrine on pentobarbital hypnosis in mice may be related to serotonergic system. The present study was undertaken to investigate the interaction of tetrandrine and different 5-HT receptors on pentobarbital-induced sleep by using the loss-of-righting reflex method. The results showed that augmentative effect of tetrandrine on pentobarbital hypnosis in mice were potentiated by the p-MPPI （5-HT1A receptor antagonist） （1 mg/kg, i.p.） and ketanserin （5-HT2A/2C receptor antagonist） （1.5 mg/kg, i.p.）, respectively. Pretreatment with either 8-OH-DPAT （5-HT1A receptor agonist） （0.1 mg/kg, s.c.） or DOI （5-HT2A/2C receptor agonist） （0.2 mg/kg, i.p.） significantly decreased pentobarbital-induced sleep time, and tetrandrine （60 mg/kg, i.g.） significantly reversed this effect. These results suggest that both the 5-HTLA and 5-HT2A/2C subfamily may be involved in the potentiating mechanism of tetrandrine＇s effects on pantobarbital hypnosis.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Leukocyte immunoglobulin-like receptor B2:A promising biomarker for colorectal cancer

According to the latest global cancer statistics,colorectal cancer(CRC)has emerged as the third most prevalent malignant tumor across the globe.In recent decades,the medical field has implemented several levels of CRC screening tests,encompassing fecal tests,endoscopic examinations,radiological examinations and blood tests.Previous studies have shown that leukocyte immunoglobulin-like receptor B2(LILRB2)is involved in inhibiting immune cell function,immune evasion,and promoting tumor progression in acute myeloid leukemia and nonsmall cell lung cancer.However,its interaction with CRC has not been reported yet.Recently,a study published in the World Journal of Gastroenterology revealed that LILRB2 and its ligand,angiopoietin-like protein 2,are markedly overexpressed in CRC.This overexpression is closely linked to tumor progression and is indicative of a poor prognosis.The study highlights the potential of utilizing the concentration of LILRB2 in serum as a promising biomarker for tumors.However,there is still room for discussion regarding the data processing and analysis in this research.