The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.

Lipid-lowering effects of gefarnate in statin-treated patients with residual hypertriglyceridemia:a randomized controlled study

BACKGROUND The prevention of coronary artery disease(CAD)faces dual challenges:the aspirin-induced gastrointestinal injury,and the residual cardiovascular risk after statin treatment.Geraniol acetate(Gefarnate)is an anti-ulcer drug.It was reported that geraniol might participate in lipid metabolism through a variety of pathways.The aim of this study was to assess the lipid-lowering effects of gefarnate in statin-treated CAD patients with residual hypertriglyceridemia.METHODS In this prospective,open-label,randomized,controlled trial,69 statin-treated CAD patients with residual hypertriglyceridemia were randomly assigned to gefarnate group and control group,received gefarnate(100 mg/3 times a day)combined with statin and statin alone,respectively.At baseline and after one-month treatment,the levels of plasma triglyceride,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and total cholesterol were tested.RESULTS After one-month gefarnate treatment,triglyceride level was significantly lowered from 2.64 mmol/L to 2.12 mmol/L(P=0.0018),LDL-C level lowered from 2.7 mmol/L to 2.37 mmol/L(P=0.0004),HDL-C level increased from 0.97 mmol/L to 1.17mmol/L(P=0.0228).Based on statin therapy,gefarnate could significantly reduce the plasma triglyceride level(P=0.0148)and increase the plasma HDL-C level(P=0.0307).Although the LDL-C and total cholesterol levels tended to decrease,there was no statistically significant difference.CONCLUSIONS The addition of gefarnate to statin reduced triglyceride level and increased HDL-C level to a significant extent compared to statin alone in CAD patients with residual hypertriglyceridemia.This suggested that gefarnate might provide the dual benefits of preventing gastrointestinal injury and lipid lowering in CAD patients.

Analysis of cancer incidence and mortality data in Heilongjiang province cancer registries, China, 2015

Objective In recent years, the rising incidence of cancer has increased patients’ living and economic burdens. This study analyzed the incidence and death due to malignant tumors in tumor registries in Heilongjiang province (China) in 2015 to provide a scientific basis for the prevention and treatment of malignant tumors in this province. Methods Data on tumor incidence and patient deaths were collected from seven tumor registries in Heilongjiang province (China) in 2015. According to the stratification of urban and rural areas and patient sex, the crude, standard, and accumulative rates (0–74 years of age) were calculated. The 2000 China Population Census data and Segi’s standard population were used to calculate the age-standardized rates. Results In 2015, the incidence rate of malignant tumors in Heilongjiang cancer registries was 259.90/100 000. The age-standardized incidence rates in the Chinese and world standard populations were 158.89/100 000 and 155.06/100 000, respectively, with a cumulative incidence rate (0–74 years) of 17.68%. The incidence of malignant tumors in urban areas was 273.55/100 000, while that in rural areas was 220.32/100 000. The incidence of malignant tumors in men was 270.89/100 000, higher than that in women (249.04/100 000). Lung cancer had the highest incidence, followed by breast cancer, liver cancer, colorectal cancer, and thyroid cancer. The mortality rate of malignant tumors in Heilongjiang cancer registries was 164.69/100 000. The age-standardized mortality rates in Chinese and in world standard populations were 95.29/100 000 and 94.35/100 000, respectively, with a cumulative mortality rate (0–74 years) of 10.44%. The mortality rate of malignant tumors in urban areas was 169.51/100 000, while that in rural areas was 150.72/100 000. The mortality rate of malignant tumors in men was 201.64/100 000, higher than that in women (128.21/100 000). Lung cancer had the highest mortality, followed by liver cancer, stomach cancer, colorectal cancer, and breast cancer. Conclusion Lung, liver, breast, and colorectal cancers were the most common cancers in Heilongjiang province, China, and should be considered the key cancer types for prevention and treatment. Moreover, the incidence of thyroid cancer is increasing, and thus early preventative measures should be implemented.

Analysis of cancer incidence and mortality in Heilongjiang cancer registries, 2016

Background:Cancer incidence rate has been increasing in recent years,and it has improved people’s living and financial burden.The incidence and mortality of malignant tumors in the Heilongjiang cancer registry area in 2016 were analyzed,which provided a scientific basis for the prevention and treatment of malignant tumors in Heilongjiang.Methods:The incidence and death data of tumors were collected from 10 tumor registration areas in Heilongjiang Province in 2016.According to the stratification of urban and rural areas and gender,the crude rate,standard rate,accumulative rates(0–74 years old)were calculated.The China 2000 population census data and Segi’s standard population were used for calculating age-standardized rates.Results:The incidence rate of malignant tumors in the Heilongjiang cancer registry area was 286.05/100,000 in 2016,age-standardized incidence rates by standard Chinese population and by standard world population were 168.11/100,000 and 164.69/100,000 with the cumulative incidence rate(0–74 years old)of 18.55%.The incidence of malignant tumors in urban areas was 313.60/100,000,and that in rural areas was 212.26/100,000.The frequency of malignant tumors in males was 295.94/100,000,higher than that in females(276.40/100,000).Lung cancer had the highest incidence followed by breast cancer,colorectal cancer,liver cancer and thyroid cancer.The mortality rate of malignant tumors in Heilongjiang cancer registration areas was 183.56/100,000,age-standardized mortality rates by standard Chinese population and by standard world population were 99.89/100,000 and 99.78/100,000 with the cumulative mortality rate(0–74 years old)of 10.95%.The mortality rate of malignant tumors in urban areas was 194.69/100,000,and that in rural areas was 153.73/100,000.The mortality rate of the male malignant tumor was 222.55/100,000,higher than that of a female malignant tumor(145.51/100,000).Lung cancer had the highest mortality followed by liver cancer,colorectal cancer,gastric cancer and breast cancer.Conclusion:Lung cancer,liver cancer,breast cancer and colorectal cancer were the most common cancers in Heilongjiang Province,which should be taken as the key cancer species for prevention and treatment.The incidence of thyroid cancer is higher in Heilongjiang Province,but the mortality rate is lower,which also needs attention.

Development status of novel spectral imaging techniques and application to traditional Chinese medicine

Traditional Chinese medicine(TCM)is a treasure of the Chinese nation,providing effective solutions to current medical requisites.Various spectral techniques are undergoing continuous development and provide new and reliable means for evaluating the efficacy and quality of TCM.Because spectral techniques are noninvasive,convenient,and sensitive,they have been widely applied to in vitro and in vivo TCM evaluation systems.In this paper,previous achievements and current progress in the research on spectral technologies(including fluorescence spectroscopy,photoacoustic imaging,infrared thermal imaging,laser-induced breakdown spectroscopy,hyperspectral imaging,and surface enhanced Raman spectroscopy)are discussed.The advantages and disadvantages of each technology are also presented.Moreover,the future applications of spectral imaging to identify the origins,components,and pesticide residues of TCM in vitro are elucidated.Subsequently,the evaluation of the efficacy of TCM in vivo is presented.Identifying future applications of spectral imaging is anticipated to promote medical research as well as scientific and technological explorations.

Upregulation of histone H3 caused by CRYAA may contribute to the development of age-related cataract

Objective:Age-relate cataract(ARC)is a disease of the eyes with no effective drugs to prevent or treat patients.The aim of the present study is to determine whether histone H3,αA-crystallin(CRYAA),β-galactosidase(GLB1),and p53 are involved in the pathogenesis of ARC.Methods:A total of 99 anterior lens capsules(ALCs)of patients with ARC of various nuclear grades,ultraviolet models of ALCs,and two human lens epithelial cell lines(FHL-124 and SRA01/04)were used,and the expression of histone H3,CRYAA,GLB1,and p53 were detected by immunoblotting and reverse transcription and real time-quantitative polymerase chain reaction.The association between CRYAA with histone H3,GLB1,and p53 was assessed in FHL-124 and SRA01/04 cells following CRYAA overexpression.Results:Histone H3 and p53 in ALCs of patients with ARC were up-regulated in a grade-dependent manner,and the expression of CRYAA showed a positive association with histone H3,p53,and GLB1.In UV models of ALCs and human lens epithelial cell lines,the expression levels of histone H3,cell apoptosis factors(Bax/Bcl-2,cleaved caspase-3),and inflammation factors(interleukin-6,tumor necrosis factor-α)were all up-regulated.Furthermore,transfection of CRYAA in FHL-124 cells induced overexpression of histone H3.Conclusion:CRYAA-mediated upregulation of histone H3 may be involved in the pathogenesis of ARC.p53 may also have a role in ARC development,but not via the CRYAA-histone H3 axis.The results of the present study may assist in improving our understanding of the pathogenesis of ARC and in identifying potential targets for treatment.

CPAL, as a New Mediator of Cardiomyocyte Metabolic Alterations and Pyroptosis, Regulates Myocardial Infarction Injury in Mice

Myocardial infarction (MI), the most serious of the ischemic heart diseases, is accompanied by myocardial metabolic disorders and the loss of cardiomyocytes. Increasing evidence has shown that long noncoding RNAs (lncRNAs) are involved in various pathological conditions such as cancer and cardiovascular diseases (CVDs), and are emerging as a novel biomarker for these disorders. This study aims to investigate the regulatory role and mechanisms of lncRNAs in myocardial remodeling in the setting of MI. We find that post-infarcted hearts exhibit a reduction of adenosine triphosphate (ATP) and an alteration of the glucose and lipid metabolism genes cluster of differentiation 36 (CD36), hexokinase 1 (HK1), and clucose transporter 4 (GLUT4), accompanied by cardiomyocyte pyroptosis. We then identify a previously unknown conserved lncRNA, AK009126 (cardiomyocyte pyroptosis-associated lncRNA, CPAL), which is remarkably upregulated in the myocardial border zone of MI mice. Importantly, the adeno-associated virus 9 (AAV9)-mediated silencing of endogenous CPAL by its short hairpin RNA (shRNA) partially abrogates myocardial metabolic alterations and cardiomyocyte pyroptosis during MI in mice. Mechanistically, CPAL is shown to bind directly to nuclear factor kappa B (NFκB) and to act as an activator of NFκB to induce NFκB phosphorylation in cardiomyocytes. We also find that CPAL upregulates caspase-1 expression at the transcriptional level and consequently promotes the release of interleukin (IL)-18 and IL-1β from cardiomyocytes. Collectively, our findings reveal the conserved lncRNA CPAL as a new regulator of cardiac metabolic abnormalities and cardiomyocyte pyroptosis in the setting of MI and suggest CPAL as a new therapeutic target to protect cardiomyocytes against ischemic injury in infarcted hearts.

Pharmacodynamics of frigid zone plant Taxus cuspidata S.et Z.against skin melanin deposition,oxidation,inflammation and allergy

Background:Taxus cuspidata S.et Z.is a precious species of frigid zone plant belonging to the Taxaceae family,which possesses anticancer,anti-inflammatory,hypoglycemic,and antibacterial pharmacological properties.While taxane extracted from Taxus chinensis has been reported to elicit antioxidant activities,whether Taxus cuspidata S.et Z.has skin-protective actions against injuries remained unknown.This study aims to explore the pharmacological effects of three Taxus extracts on skin melanin deposition,oxidation,inflammation,and allergy so as to provide new ideas for the prevention and treatment of various diseases related to skin damage.Methods:Skin melanin deposition was evaluated by measuring melanin content in the skin of guinea pigs by alkali lysis method.Antioxidant capacity was evaluated by measuring superoxide dismutase(SOD)concentration and glutathione(GSH)content in skin tissue homogenates of Kunming mice by SOD assay kit and micro reduced GSH assay kit.The quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting were used to examine the levels of both SOD and recombinant glutathione peroxidase 4(GPX4).Skin inflammation was evaluated by xylene-induced ear swelling test and egg-white-induced paw swelling test in mice.In a mouse model of skin allergy induced by 4-aminopyridine(4-AP),allergy was determined by licking body counts and histamine concentrations in tissue homogenates using enzyme-linked immunosorbent assay(ELISA)kits.Two proinflammatory factors tumor necrosis factor(TNF)-αand interleukin(IL)-1βwere measured by qRT-PCR.Hematoxylin and eosin(HE)staining was conducted to assess the degree of skin lesion.Results:All three Taxus extracts including Taxus chinensis essential oil,Taxus chinensis extract and Taxus chinensis extract compound reduced the melanin deposits in the back skin relative to the non-treated control animals,of which Taxus chinensis essential oil produced the greatest effect.In contrast,the three Taxus extracts elevated SOD and GSH levels in the skin tissues,and the highest increase was seen with Taxus chinensis essential oil.Three Taxus extracts,especially Taxus chinensis essential oil,effectively reduce the rate of ear and paw swelling.All three Taxus extracts reduced the number of body licks,the levels of TNF-αand IL-1β,and the histamine content in tissue homogenates of mice and alleviated skin damage.Consistently,Taxus chinensis essential oil yielded the greatest magnitude of decreases.Conclusion:While all three Taxus extracts possessed the anti-skin melanin deposition,oxidation,and allergy properties,Taxus chinensis essential oil produced the superior effects.

Incidence and mortality of cervical cancer in China,2013

Objective： Estimating the incidence and mortality rate of cervical cancer became necessary to establish prevention measures and healthy policies. The aim of this study was to estimate the updated incidence and mortality rate of cervical cancer in 2013 in China. Methods： According to the evaluation criteria developed by the National Central Cancer Registry of China, the data submitted from 255 cancer registries met the required standards in 2013. Cervical cancer cases were retrieved from the national database and combined with the 2013 national population data. The age-standardized incidence and mortality rates were based on the demographic structure of the national census 2000 and Segi＇s world population. Results： In 2013, the estimated number of new cases and deaths from cervical cancer were 100,700 and 26,400, respectively. The etude incidence of cervical cancer was 15.17/100,000. The age-standardized incidence rates based on the Chinese standard population （ASIRC） and the world standard population （ASIRW） were I 1.30/100,000 and I0.30/100,000, respectively. The incidence of cervical cancer in urban areas was 15.62/100,000 and the ASIRC was 11.12/100,000. The incidence of cervical cancer in rural areas was 14.65/100,000 and the ASIRC was 11.47/100,000. The mortality rate of cervical cancer was 3.98/100,000. The age-standardized mortality rates based on the Chinese （ASMRC） and world standard populations （ASMRW） were 2.76/100,000 and 2.62/100,000, respectively. The mortality rate of cervical cancer in urban areas was 3.85/100,000 and in rural areas was 4.14/100,000. Cervical cancer incidence and mortality increased with age. Urban areas had a higher incidence of cervical cancer and lower mortality rates when compared with rural areas. Conclusions： Dynamic monitoring of cervical cancer incidence and mortality is the fundamental work of cervical cancer prevention and control. Cervical cancer is a serious issue in women＇s health, and prevention strategies need to be enhanced, such as human papilloma virus （HPV） vaccination and screening programs.

Retreatment of a patient who presented with synchronous multiple primary colorectal carcinoma: report of a case

It is well known that one-stage resection of synchronous multiple primary colorectal carcinoma is an ideal choice if the patient＇s physical condition is not bad. Detailed examination of the whole intestinal tract is very important for patients with colorectal cancer, which could prevent patients from receiving repeat treatment to a great extent. We present a case report of a patient with synchronous primary colorectal cancer. Because pre-or intra-operative examination is not sufficient at his first consultation, the patient had undergone multiple operations after receiving chemotherapy, radiotherapy and intestinal stent insertion, which results in peritoneal adhesions formation. The preoperative placement of prophylactic ureteral catheters facilitated recognition of ureters in operation that assure the prevention of ureteral injuries. If not aware of the importance of detailed preoperative examination and standardized treatment can lead to wrong treatment as in this case. Prophylactic ureteral catheters might assist in their immediate recognition.

Tranilast treats cold-related hypertension by reducing the expression of NLRP3 inflammasome

Objective:Cold exposure is associated with increased prevalence of hypertension and the related severe cardiovascular events.Aberrant activation of the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome plays an important role in the development of hypertension.Tranilast(TR),an inhibitor of NLRP3,provides a useful pharmacological probe for exploring the role of NLRP3 in pathogenesis associated with inflammation and its potential application as a therapeutic agent.This study was designed to examine the effects of TR on NLRP3 and hypertension in rats exposed to cold environment to simulate the frigid-zone conditions.Methods and results:Sprague Dawley(SD)rats were exposed to moderate cold temperature(4±1℃),and then were randomized to receive TR or vehicle for 3 weeks,while the control group was raised under rat room temperature(RT,23±1℃).We found that cold exposure substantially increased blood pressure,NLRP3 inflammasome level,and fibrosis in aorta,which were reversed by TR.Conclusion:TR has an anti-hypertensive property in cold environment,and this beneficial action is likely conferred by its inhibitory effects on inflammation and fibrosis.These findings suggest TR as a potential drug for the treatment of cold-induced hypertension.

The role of HSPB1 and ectopic F1Fo-ATPase interaction in hypoxia pulmonary hypertension vascular adventitial vasa vasorum remodeling

OBJECTIVE To investigate the role of adventitial vasa vasorum in artery remodeling during the process of pulmonary artery hypertension(PAH),we checked the small heat shock protein 27/25(HSPB1)whether involved in pathological basis of vascular remodeling.METHODS We explored the potential role of HSPB1 interacts with ectopic F1Fo-ATPase in the pulmonary vascular remodeling,investigate its effects on the endothelium cell dynamic,and further reveal its possible molecular mechanisms using hypoxic pulmonary hypertension rat model,transgenic mice and pulmonary adventitial vasa vasorum endothelial cell culture in vitro.RESULTS Our studies have shown that HSPB1 improves adventitial vasa vasorum angiogenesis and remodeling.We found that hypoxia induces-HSPB1 upregulation and HSPB1 interact with ectopic F1Fo-ATPase modulate adventitial vasa vasorum endothelial cell proliferation,migration and tube formation.And the inhibition of HSPB1can reverse the vascular inflammation and fibrosis amazingly.CONCLUSION Adventitial vasa vasorum plays an important role in vascular remodeling,and small heat shock protein 27/25 was involved in a variety of diseases during the development of PAH,which could an efficient therapeutic targets and prevention strategy for PAH clinical.

Apelin aggravates the migration and invasion of non-small cell lung cancer cells via YAP1

Background:Apelin,an endogenous ligand of G-protein coupled receptor(GPCR),is a secreted peptide involved in the development of various tumors.However,the relationship between apelin and non-small cell lung cancer(NSCLC)is not quite clear.This study was designed to investigate the effect and mechanism of apelin on cell proliferation,migration and invasion of NSCLC cells.Methods:Twelve NSCLC specimens were collected for hematoxylin-eosin(HE)staining and immunohistochemistry analyses.Cell proliferation was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and cell migration and invasion were assessed using wound-healing and transwell assays.The subcellular location of yes associated protein 1(YAP1)in A549 cells was determined by immunofluorescence.The mRNA and protein levels in NSCLC tissues and cell lines were measured by qRT-PCR and western blot,respectively.Results:Apelin was upregulated in tumor tissues compared with the adjacent tissues.Apelin promoted proliferation,migration,and invasion of A549 and H460 cells,which was reversed by competitive apelin receptor(APJ)antagonist ML221.Additionally,apelin upregulated YAP1 expression,whereas silence of YAP1 by small interfering RNA(siRNA)attenuated apelin-induced cell proliferation,migration and invasion and suppressed epithelial-mesenchymal transition progression.Conclusion:Apelin promotes NSCLC cells proliferation,migration,and invasion by modulating YAP1 and might be a potential therapeutic target for NSCLC treatment.

Traditional Chinese medicine in the treatment of high incidence diseases in cold areas: the thrombotic diseases

Thrombotic diseases are the leading causes of death worldwide,especially in cold climates.Traditional Chinese medicine(TCM)-based therapies have gained increasing popularity worldwide,but also raised some concerns about its efficacy,safety profile and exact mechanisms.TCM has been traditionally used in the management of thrombosis and convincingly proven effective in modifying thrombosis progression,particularly the platelet function,coagulation system and fibrinolytic system.This review article focuses on TCM regulation of thrombosis with brief discussion on the fundamental aspects and relevant background information for better understanding of the subject.In addition to its antithrombotic effects,we will dive insight into the cellular and molecular mechanisms of TCM as pharmacological regulators of platelet aggregation,coagulation,and fibrinolysis.With increasing awareness and understanding of the benefits and potentials of TCM,TCM products will in no doubt gain its broader applications in the treatment of thrombosis and associated disorders,which in turn will deepen our understanding of its pharmacological and molecular mechanisms.Finally,current review provides a perspective view on the future directions to TCM research on thrombosis.

Overexpression of microRNA-135b-5p attenuates acute myocardial infarction injury through its anti-oxidant and anti-apptotic properties

Objective:Myocardial infarction(MI)remains the leading cause of morbidity and mortality due partly to the limited regenerative capacity of cardiomyocytes to replace cardiomyocyte lost due to apoptosis.Inhibiting cardiomyocyte apoptosis is recognized as an effective therapeutic approach for MI.MicroRNAs(miRNAs,miRs),which regulate target genes at the post-transcriptional level,play a significant role in the regulation of cardiovascular diseases such as MI.MicroRNA-135b(miR-135b)has a protective effect on cardiomyocytes.However,the role of miR-135b in cardiomyocyte apoptosis in infarct myocardium needs further clarification.Methods:We generatedα-MHC-miR-135b transgenic mice to investigate the role of miR-135b in myocardial injury after MI.MiR-135b mimic and negative control(NC)were transfected into H2O2-induced cardiomyocytes to evaluate the effect of overexpression of miR-135b on the levels of reactive oxygen species(ROS)and apoptosis.Results:Our results showed that overexpression of miR-135b had protective effect on cardiomyocyte injury both in vivo and in vitro.MiR-135b inhibited cardiomyocyte apoptosis and ROS generation,downregulated pro-apoptosis proteins(cleaved-caspase-3 and Bax),and increased anti-apoptosis protein(Bcl-2).Moreover,miR-135b showed an inhibitory effect on apoptosis-related protein target transient receptor potential vanilloid-type 4(TRPV4)cation channel.Conclusion:MiR-135b might be considered a new molecular target for potential replacement therapy as antiapoptotic cardioprotection in the setting of MI.

糖组与糖医学

Among the four equally important major building blocks of life-that is,nucleic acids(DNA and RNA),proteins,lipids,and car-bohydrates(glycans)-the first two,DNA and RNA,follow the well-established principle of the“central dogma”of transcription(DNA to RNA)and translation(RNA to protein).However,the latter two,glycans and lipids,are missing from biology’s central dogma.In fact,there may be an undiscovered law regarding communication between DNA,RNA,glycans,and lipids,and their roles in immunomodulation.Thus,it becomes necessary to ask:Does a paracentral dogma exist?Can glycans be the third life code-after the first and second life codes of nuclei acids and amino acids-for the materiality of the cell?

Unveiling metabolic flux changes during acute cold exposure

Controlling energy expenditure during acute cold exposure is a fundamental aspect of metabolic dynamics in organisms.However,prior studies on cold-induced thermogenesis faced limitations,primarily focusing on brown adipose tissue(BAT)and lacking precise in vivo flux measurements.This editorial aims to highlight the recent research by Bornstein et al.providing a comprehensive and quantitative insight into the intricate alterations in metabolic flux that drive this phenomenon[1].

Neutrophil extracellular traps mediate the crosstalk between glioma progression and the tumor microenvironment via the HMGB1/RAGE/IL-8 axis

Objective:Neutrophil extracellular traps(NETs)produced by tumor-infiltrating neutrophils(TINs)are associated with poor prognosis in patients with several types of cancer.However,the mechanisms underlying the involvement of NETs in glioma progression remain largely unknown.This study aimed to elucidate the roles of NETs in biological processes that drive the crosstalk between glioma progression and the tumor microenvironment.Methods:Neutrophil infiltration and NETs formation were investigated in glioma tissue through immunohistochemistry,and their relationships with clinicopathological features and outcomes were statistically evaluated.The effects of NETs on glioma cell progression were studied in a co-culture system.In vivo and in vitro experiments validated the reactive oxygen species activity and cytokine production of TINs,as well as the ERK signaling pathway activation and the metastasis of gliomas.Results:Neutrophil infiltration and NETs formation were induced in high-grade glioma compared with low-grade glioma.NETs induced by TINs were determined to be an oncogenic marker of high-grade gliomas and to be involved in cell proliferation and invasion.NETs overproduction promoted glioma cell proliferation,migration,and invasion.Furthermore,HMGB1 was found to bind to RAGE and activate the NF-κB signaling pathway in vitro.In addition,NETs stimulated the NF-κB signaling pathway,thus promoting IL-8 secretion in glioblastoma.Subsequently,IL-8 recruited neutrophils which in turn mediated NETs formation via the PI3 K/AKT/ROS axis in TINs.Conclusions:Our results suggest that NETs produced by TINs mediate the crosstalk between glioma progression and the tumor microenvironment by regulating the HMGB1/RAGE/IL-8 axis.Targeting NETs formation or IL-8 secretion may be an effective approach to inhibit glioma progression.

Exosomes secreted from cardiomyocytes suppress the sensitivity of tumor ferroptosis in ischemic heart failure

Heart failure(HF)patients in general have a higher risk of developing cancer.Several animal studies have indicated that cardiac remodeling and HF remarkably accelerate tumor progression,highlighting a cause-and-effect relationship between these two disease entities.Targeting ferroptosis,a prevailing form of non-apoptotic cell death,has been considered a promising therapeutic strategy for human cancers.Exosomes critically contribute to proximal and distant organ-organ communications and play crucial roles in regulating diseases in a paracrine manner.However,whether exosomes control the sensitivity of cancer to ferroptosis via regulating the cardiomyocyte-tumor cell crosstalk in ischemic HF has not yet been explored.Here,we demonstrate that myocardial infarction(MI)decreased the sensitivity of cancer cells to the canonical ferroptosis activator erastin or imidazole ketone erastin in a mouse model of xenograft tumor.Post-MI plasma exosomes potently blunted the sensitivity of tumor cells to ferroptosis inducers both in vitro in mouse Lewis lung carcinoma cell line LLC and osteosarcoma cell line K7M2 and in vivo with xenograft tumorigenesis model.The expression of miR-22-3p in cardiomyocytes and plasma-exosomes was significantly upregulated in the failing hearts of mice with chronic MI and of HF patients as well.Incubation of tumor cells with the exosomes isolated from post-MI mouse plasma or overexpression of miR-22-3p alone abrogated erastin-induced ferroptotic cell death in vitro.Cardiomyocyte-enriched miR-22-3p was packaged in exosomes and transferred into tumor cells.Inhibition of cardiomyocyte-specific miR-22-3p by AAV9 sponge increased the sensitivity of cancer cells to ferroptosis.ACSL4,a pro-ferroptotic gene,was experimentally established as a target of miR-22-3p in tumor cells.Taken together,our findings uncovered for the first time that MI suppresses erastin-induced ferroptosis through releasing miR-22-3p-enriched exosomes derived from cardiomyocytes.Therefore,targeting exosome-mediated cardiomyocyte/tumor pathological communication may offer a novel approach for the ferroptosis-based antitumor therapy.

Bionic peptide scaffold in situ polarization and recruitment of M2 macrophages to promote peripheral nerve regeneration

Tissue regeneration requires exogenous and endogenous signals,and there is increasing evidence that the exogenous microenvironment may play an even more dominant role in the complex process of coordinated multiple cells.The short-distance peripheral nerve showed a spontaneous regenerative phenomenon,which was initiated by the guiding role of macrophages.However,it cannot sufficiently restore long-distance nerve injury by itself.Based on this principle,we firstly constructed a proinflammatory model to prove that abnormal M2 expression reduce the guidance and repair effect of long-distance nerves.Furthermore,a bionic peptide hydrogel scaffold based on self-assembly was developed to envelop M2-derived regenerative cytokines and extracellular vesicles(EVs).The cytokines and EVs were quantified to mimic the guidance and regenerative microenvironment in a direct and mild manner.The bionic scaffold promoted M2 transformation in situ and led to proliferation and migration of Schwann cells,neuron growth and motor function recovery.Meanwhile,the peptide scaffold combined with CX3CL1 recruited more blood-derived M2 macrophages to promote long-distance nerve reconstruction.Overall,we systematically confirmed the important role of M2 in regulating and restoring the injury peripheral nerve.This bionic peptide hydrogel scaffold mimicked and remodeled the local environment for M2 transformation and recruitment,favoring long-distance peripheral nerve regeneration.It can help to explicate regulative effect of M2 may be a cause not just a consequence in nerve repair and tissue integration,which facilitating the development of pro-regenerative biomaterials.