High-intensity swimming alleviates nociception and neuroinflammation in a mouse model of chronic postischemia pain by activating the resolvin E1-chemerin receptor 23 axis in the spinal cord

Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.

Interactions of primary insult biomechanics and secondary cascades in spinal cord injury： implications for therapy

The complex and variable nature of traumatic spinal cord inju- ry （SCI） presents a unique challenge for translational research. SCI is not bound by any demographic nor is it limited to specific injury biomechanics.

Targeting neuroinflammation after therapeutic hypothermia for perinatal hypoxic-ischemic brain injury

Hypoxic-ischemic encephalopathy(HIE)has an incidence of 1-3 in 1000 term births in high-income countries(Zhou et al.,2020).The standard treatment for these infants is therapeutic hypothermia.Although therapeutic hypothermia significantly reduces the risk of death and disability for infants with HIE,it is still only partially protective as up to 45%of infants still develop disability despite treatment(Zhou et al.,2020).The current therapeutic hypothermia protocol is optimal for widespread use in infants with moderate to severe HIE.However,it is possible that a more tailored approach for individual babies,including stratification of the cooling regimen for the severity of HIE and the identification of reliable biomarkers to guide treatment,may improve efficacy in the future.

Template-Based Gait Authentication Through Bayesian Thresholding

While gait recognition is the mapping of a gait sequence to an identity known to the system, gait authentication refers to the problem of identifying whether a given gait sequence belongs to the claimed identity. A typical gait authentication system starts with a feature representation such as a gait template, then proceeds to extract its features, and a transformation is ultimately applied to obtain a discriminant feature set. Almost every authentication approach in literature favours the use of Euclidean distance as a threshold to mark the boundary between a legitimate subject and an impostor. This article proposes a method that uses the posterior probability of a Bayes' classifier in place of the Euclidean distance. The proposed framework is applied to template-based gait feature representations and is evaluated using the standard CASIA-B gait database. Our study experimentally demonstrates that the Bayesian posterior probability performs significantly better than the de facto Euclidean distance approach and the cosine distance which is established in research to be the current state of the art.

Severe &Moderate BPH Symptoms in Mid-Aged Men Improve with Isoflavonoid-Equol Treatment: Pilot Intervention Study

Benign prostatic hyperplasia (BPH) is the pathological cellular progression of glandular proliferation associated with aging. Current available treatment options for BPH have limitations and various adverse effects. Equol is a polyphenolic/isoflavonoid molecule derived from intestinal metabolism, dairy and dietary plant sources. It has the unique characteristic to bind specifically 5α-dihydrotestosterone (5α-DHT) by sequestering 5α-DHT from the androgen receptor, thus decreasing androgen hormone actions to improve prostate health by acting as a selective androgen modulator (SAM). It also has affinity for estrogen related receptor gamma (ERR-γ) and estrogen receptor beta (ER-β) within the prostate that is known to improve male health via selective estrogen receptor modulatory (SERM) activities to decrease inflammation, cellular proliferation and carcinogenesis. We investigated the possible clinical efficacy of equol on the symptoms associated with benign prostatic hyperplasia (BPH) in this study. Materials and Methods: We performed a pilot intervention study evaluating the effects of low dose oral equol supplement (6 mg, twice a day with meals) for 4 weeks in a total of 18 men (49 - 60 years old) with moderate or severe BPH. Subjects included in the study: gave informed consent, underwent a physical examination and verified their BPH symptoms as measured by the International Prostate Symptom Scores (IPSS) and then were assigned to the moderate or severe BPH groups based upon their total IPSS index. All adverse events were reported. The primary efficacy measure was the IPSS parameters comparing baseline to 2 and 4 week IPSS indices. Blood samples were collected at the baseline and 4th week visits that served as secondary efficacy parameters that included testosterone, 5α-DHT and general blood chemistries along with cardiac and hepatic function panels. Results: Low dose equol positively improved moderate to severe BPH symptoms according to the IPSS indices. In moderately symptomatic men (n = 10) 5 out of 7 of the IPSS parameters significantly improved by 4 weeks of equol treatment. In severely symptomatic men (n = 8) all 7 of the IPSS parameters significantly improved with 4 weeks of equol treatment. There were no significant changes in androgen levels, general blood chemistries or cardiac and hepatic function parameters. Although, 5α-DHT levels declined by 21% in severely symptomatic men (from baseline vs. 4 week values). Conclusion: These findings suggest that equol may provide a well tolerated and rapid beneficial therapy for BPH that can be used alone or in combination with current pharmaceutical therapies. The beneficial clinical efficacy of equol observed in this study may be due to the multiple positive biological actions that are not present in current pharmaceutical treatments.

Does Ethanol Play a Pro-Oxidant Role during Oxidative Stress in the Liver?

Oxidative stress has been implicated in the pathophysiology of liver injury during xenobiotic and alcohol metabolism, ischemia/reperfusion injury. In this study we examined if ethanol acted as a pro-oxidant making cells become more sensitive to tert-butylhydroperoxide (tBH) killing. Cell viability was determined in a rat hepatoma cell line (FTO2B) and rat primary hepatocytes in culture in the presence or absence of ethanol pretreatment. To elucidate the contribution of labile iron, deferoxamine (DF, an iron chelator) or lipid free radicals, N,N-diphenyl-p-phenylenediamine (DPPD, a lipid scavenger) were added to the ethanol tBH co-treatment. The levels of glutathione (GSH) and glutathione disulfide (GSSG) in the hepatocytes were also measured. Ethanol treatment (both pretreatment and co-treatment during the 3-hr tBH exposure) increased cell killing dramatically in both FTO2B cells and primary rat hepatocytes. Both DF and DPPD decreased ethanol-enhanced tBH cell killing in hepatocytes. These results demonstrated that co-treatment of FTO2B cells and primary rat hepatocytes with ethanol and tBH increased cell killing. The GSH level was dramatically reduced while GSSG level rose. Both DFP and DPPD reversed or protected the cells from this insult, indicating that ethanol was a pro-oxidant.

Review: Anti-Oxidant and Anti-Aging Properties of Equol in Prostate Health (BPH)

Benign prostatic hyperplasia (BPH) is the pathological cellular progression of glandular proliferation associated with aging. The primary changes in prostate disorders are mediated by the conversion of the principle androgen, testosterone, to its more potent metabolite, 5α-dihydrotestosterone (5α-DHT). However, recent evidence suggests that estrogen hormonal actions via estrogen receptor subtypes also play an important role in BPH. Current pharmaceutical options for BPH have advantages, limitations and adverse effects. Complementary and Alternative Medicine (CAM) treatments for BPH include botanicals such as polyphenols and isoflavones. Equol is a polyphenolic/isoflavonoid molecule derived from intestinal metabolism, dairy and dietary plant sources. Equol has potent anti-oxidant and anti-aging properties to decrease prostatic irritation and potentially neoplastic growth. It has the unique characteristic to bind specifically 5α-DHT by sequestering 5α-DHT from the androgen receptor (AR), thus decreasing androgen hormone actions to improve prostate health by acting as a selective androgen modulator (SAM). It also has affinity for estrogen related receptor gamma (ERR-γ) and estrogen receptor beta (ER-β) within the prostate that is known to improve male health via selective estrogen receptor modulatory (SERM) activities to decrease inflammation, cellular proliferation and carcinogenesis. The possible clinical efficacy of equol on the symptoms associated with BPH is presented and the reviewed findings suggest that equol may provide a well-tolerated and rapid beneficial therapy for BPH that can be used alone or in combination with current pharmaceutical therapies. The beneficial clinical efficacy of equol observed may be due to the multiple positive biological actions that are not present in current pharmaceutical treatments.

Crotonylation of PRKACA enhances PKA activity and promotes colorectal cancer development via the PKA-FAK-AKT pathway

Colorectal cancer (CRC) is a common cancer with high morbidity and mortality.1 Post-translational modification (PTM) of protein plays an important role in the pathogenesis of CRC. Lysine crotonylation (Kcr) is an important type of PTM and has been proved evolutionarily conserved in eukaryotic cells from a wide range of species.2 However, the role of protein Kcr in the progression of CRC is unclear.

Corrigendum to"Crystal structure of RNA helicase from Saint Louis encephalitis virus and discovery of its inhibitors"[Genes Dis 10(2023)389-392]

We're very sorry for missing a funding program in funding section.Here,we would like to add this program:The Natural Science Foundation of Tianjin(China)(No.21JCQNJCO1890)from Tianjin Science and Technology in the first place.The authors would liketo apologise forany inconvenience caused.

Crystal structure of RNA helicase from Saint Louis encephalitis virus and discovery of its inhibitors

St. Louis encephalitis virus (SLEV) was first recognized in 1933 and caused a major encephalitis epidemic with 1095 clinical cases and 201 deaths in St. Louis, Missouri.1 According to the median values from 2014 to 2018, the percentage of neuroinvasion by SLEV was 62% and the fatality rate was 9% in the United States.2 The clinical symptoms of SLEV infection include neurological abnormalities such as memory loss, disorientation, and meningoencephalitis. Till now, specific treatments including vaccine and drug are unavailable for SLEV infection. It is of particular importance to get prepared for SLEV infection, especially given the currently raging global COVID-19 epidemic.

Effect of Danhong Injection(丹红注射液)on Improving Coronary Microcirculation Injury after Percutaneous Coronary Intervention

Objective:To explore the effectiveness of Danhong Injection(丹红注射液)on improving microcirculatory injury after percutaneous coronary intervention(PCI)in patients with coronary heart disease(CHD).Methods:A randomized controlled trial was conducted and 90 patients were enrolled.A random sequence was generated using statistical analysis software.Patients with microcirculatory injuries after PCI were randomly divided into 3 groups for treatment(30 subjects in each group):Danhong Injection group:after PCI,Danghong Injections were given with intravenous administration with 40 mL twice a day for a week;statins intensive group:after PCI,atorvastatin calcium tablets were given oral medication with 80 mg once,and then atorvastatin 40 mg daily for 1 week;the control group:after PCI,atorvastatin calcium tablets were given oral medication with 10–20 mg daily for 1 week.The index of microcirculation resistance(IMR)was used to assess microcirculatory injury during PCI.The IMR of the target vessel was reexamined after 1 week of drug treatment.Results:After one week's drug treatment,IMR was significantly decreased in both statins intensive group and Danhong Injection group compared with the control group(P<0.01),but no difference was found between statins intensive group and Danhong injection group(14.03±2.54 vs.16.03±5.72 U,P=0.080).Conclusions:The efficacy of Danhong Injection is non-inferior to statin.Early use of Danhong Injection after PCI can effectively improve coronary microcirculation injury after PCI.

Platinum nanoparticles promote breast cancer cell metastasis by disrupting endothelial barrier and inducing intravasation and extravasation

Breast cancer is a common malignancy in women with disappointing prognosis especially the triple-negative subtype.Recently,nanomedicine becomes a promising therapeutic strategy for breast cancer,such as platinum nanoparticles(PtNPs).Despite the promising anticancer effects of PtNPs,the safety of PtNPs remains to be fully evaluated.Herein,a series of cell and animal experiments demonstrate that PtNPs facilitate breast cancer metastasis by damaging the vascular endothelial barrier.PtNPs disrupt endothelial cell proliferation,migration and tube-like structure formation,destruct endothelial adhesions junctions and induce endothelial barrier leakiness in vitro most likely by stimulating intracellular reactive oxygen species(ROS)generation and altering the expression and conformation of endothelial junctional proteins,thus promoting intravasation and extravasation of the implanted 4T1 breast cancer cells and leading to cancer metastasis in female BALB/c nude mice in vivo.In addition,smaller PtNPs(5 nm)are more potent than larger PtNPs(70 nm)in exerting the above effects.The study provides the first evidence that PtNPs can promote breast cancer metastasis by damaging endothelial barrier.The unexpected detrimental effects of PtNPs should be considered in future nanomedicine designs for the treatment of breast cancer.

BaTiO_(3)@Au nanoheterostructure suppresses triple-negative breast cancer by persistently disrupting mitochondrial energy metabolism

Abnormal metabolism has become a potential target for highly malignant and invasive triple-negative breast cancer(TNBC)due to its relatively low response to traditional therapeutics.The existing metabolic interventions demonstrated unsatisfactory therapeutic outcomes and potential systemic toxicity,resulting from the metabolic instability and limited targeting ability of inhibitors as well as complex tumor microenvironment.To address these limitations,here we developed a robust pyroelectric BaTiO_(3)@Au core–shell nanostructure(BTO@Au)to selectively and persistently block energy generation of tumor cells.Stimulated by near-infrared(NIR)laser,the Au shell could generate heat to activate the BaTiO_(3)core to produce reactive oxygen species(ROS)regardless of the constrained microenvironment,thus prominently inhibits mitochondrial oxidative phosphorylation(OXPHOS)and reduces ATP production to induce TNBC cell apoptosis.The therapeutic effects have been well demonstrated in vitro and in vivo,paving a new way for the development of metabolic interventions.