Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular activities.Endoplasmic reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and proteostasis.In this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements.We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases.In summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders.This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

Application of Artificial Insemination in Selective Breeding of Native Beef Cattle in Wenzhou

[Objective]The paper was to improve the quality and growth rate of native yellow cattle in Wenzhou.[Method]Three groups of cattle were subjected to artificial insemination using frozen semen from Wagyu bull.The groups consisted of 20 native yellow cattle,20 Angus catle,and 20 Luxi yellow cattle.The heifers were subsequently evaluated for body size and body weight,and underwent treatment with estrus synchronization,artificial insemination,and early pregnancy diagnosis.[Result]The mean body size and body weight of native yellow cattle were found to be significantly lower than those of Angus cattle and Luxi yellow cattle(P<0.05).The estrus synchronization rate and mating rate of native yellow cattle were both 100%,while the corresponding rates for Angus cattle and Luxi yellow cattle were 90%and 95%,respectively.The ultrasound examination conducted on the 32m day following the mating revealed a distinct image of gestation sac,which,when considered alongside the findings of the rectal examination,may be indicative of pregnancy.The conception rates were 75%,72%,and 74%for native yllow cattle,Angus cattle,and Luxi yellow cattle,respectively.[Conclusion]The reproductive performance of native beef cattle is relatively superior.

Analysis on the Impact of Cattle Fattening Technology on Farmer Households in Atabae Timor-Leste

Agriculture is one of the priority sectors in Timor-Leste. Introducing new agriculture technology is crucial to enhance agricultural production. Practicing cattle fattening can increase beef cattle body weight and generate income to the beef cattle farmers. As farmers face problems including agricultural production decline, lack of forages and information and weather unfavourable. The study’s purpose was to examine the impact of adoption of cattle fattening technology on farmer households in Atabae administrative post, Bobonaro municipality in Timor-Leste. There were 200 beef cattle farmers households where randomly selected in four villages in Atabae. It consisted of 65 farmers practicing cattle fattening and 135 farmers non-practicing cattle fattening. Face to face interviews used structured questionnaire. Statistical analysis such as t-test and descriptive analysis were used to examine impact adoption of cattle fattening technology by farmers and factor constraints of cattle production and the solutions of it. The results indicated the average value of cattle and profit were significant different from zero and it is associated with practicing of cattle fattening. The average of labour used on cattle activities, the average of cattle sold, and total cost spent on cattle were not significant different from zero. The percentage of farmers said that factors constraints cattle production were shortage of water and forage (53%) and spend time on culture ceremony and lack of capital (33%). The number of farmers said that they collected water from river, feed cattle with sago and forage (55.3%) and cultivated forage (23.4%). This finding contributes information to the farmers, traders, and Timorese government to continue implementing cattle fattening activities as it enhances farmers’ income and developing cattle production.

Ferroptosis and endoplasmic reticulum stress in ischemic stroke

Ferroptosis is a form of non-apoptotic programmed cell death,and its mechanisms mainly involve the accumulation of lipid peroxides,imbalance in the amino acid antioxidant system,and disordered iron metabolism.The primary organelle responsible for coordinating external challenges and internal cell demands is the endoplasmic reticulum,and the progression of inflammatory diseases can trigger endoplasmic reticulum stress.Evidence has suggested that ferroptosis may share pathways or interact with endoplasmic reticulum stress in many diseases and plays a role in cell survival.Ferroptosis and endoplasmic reticulum stress may occur after ischemic stroke.However,there are few reports on the interactions of ferroptosis and endoplasmic reticulum stress with ischemic stroke.This review summarized the recent research on the relationships between ferroptosis and endoplasmic reticulum stress and ischemic stroke,aiming to provide a reference for developing treatments for ischemic stroke.

Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

Prevalence and Distribution of Tick-Borne Hemoparasites in Cattle from the Noun and Ndé Divisions of the West Region, Cameroon

Background and Objective: Tick-borne hemoparasitic illnesses pose a serious threat to the well-being and productivity of cattle. This study aimed to investigate the prevalence of tick-borne hemoparasites in Cameroon, with a specific focus on the Noun and Nde Divisions of the West Region. Methodology: A total of 423 cattle from 10 villages in both divisions were included in the study. Blood smears were prepared and subjected to microscopic screening for Babesia and Anaplasma parasites. Results: The prevalence of Anaplasma was found to be 23.4%, while Babesia exhibited a seroprevalence of 17.3%. Samples from Institute of Agricultural Research for Development (IRAD) and Koupa Ngangnou demonstrated significantly higher prevalence rates, potentially influenced by climate variations affecting tick populations. Additionally, 17.3% of the animals exhibited low hematocrit levels, indicative of anemia. No significant associations were observed between the presence of hemoparasite infection and cattle characteristics. Conclusion: This study provides fundamental data on the extensive distribution and impact of tick-borne hemoparasites in a significant cattle-producing region of Cameroon.

Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein(RNP)electroporation

Background Genome editing has been considered as powerful tool in agricultural fields.However,genome editing progress in cattle has not been fast as in other mammal species,for some disadvantages including long gestational periods,single pregnancy,and high raising cost.Furthermore,technically demanding methods such as microinjection and somatic cell nuclear transfer(SCNT)are needed for gene editing in cattle.In this point of view,electroporation in embryos has been risen as an alternative.Results First,editing efficiency of our electroporation methods were tested for embryos.Presence of mutation on embryo was confirmed by T7E1 assay.With first combination,mutation rates for MSTN and PRNP were 57.6%±13.7%and 54.6%±13.5%,respectively.In case of MSTN/BLG,mutation rates were 83.9%±23.6%for MSTN,84.5%±18.0%for BLG.Afterwards,the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep sequencing.Thirteen recipients were transferred for MSTN/PRNP,4 calves were delivered,and one calf underwent an induction for double KO.Ten surrogates were given double-KO embryos for MSTN/BLG,and four of the six calves that were born had mutations in both genes.Conclusions These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively applied.Finally,MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.

Diet and monensin influence the temporal dynamics of the rumen microbiome in stocker and finishing cattle

Background Stocker cattle diet and management influence beef cattle performance during the finishing stage,but knowledge of the dynamics of the rumen microbiome associated with the host are lacking.A longitudinal study was conducted to determine how the feeding strategy from the stocker to the finishing stages of production affects the temporal dynamics of rumen microbiota.During the stocker phase,either dry hay or wheat pasture were provided,and three levels of monensin were administrated.All calves were then transported to a feedlot and received similar finishing diets with or without monensin.Rumen microbial samples were collected on d 0,28,85 during the stocker stage(S0,S28 and S85)and d 0,14,28,56,30 d before slaughter and the end of the trial during the finishing stage(F0,F14,F28,F56,Pre-Ba,and Final).The V4 region of the bacterial 16S rRNA gene of 263 rumen samples was sequenced.Results Higher alpha diversity,including the number of observed bacterial features and the Shannon index,was observed in the stocker phase compared to the finishing phase.The bacterial amplicon sequence variants(ASVs)differentiating different sampling time points were identified.Dietary treatments during the stocker stage temporally impact the dynamics of rumen microbiota.For example,shared bacteria,including Bacteroidales(ASV19)and Streptococcus infantarius(ASV94),were significantly higher in hay rumen on S28,S85,and F0,while Bacteroidaceae(ASV11)and Limivicinus(ASV15)were more abundant in wheat.Monensin affected rumen microbial composition at a specific time.Transportation to feedlot significantly influenced microbiome structure and diversity in hay-fed calves.Bacterial taxa associated with body weight were classified,and core microbiotas interacted with each other during the trial.Conclusions In summary,the temporal dynamics of the rumen microbiome in cattle at the stocker and finishing stage are influenced by multiple factors of the feeding strategy.Diet at the stocker phase may temporarily affect the microbial composition during this stage.Modulating the rumen microbiome in the steers at the stocker stage affects the microbial interactions and performance in the finishing stage.

Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model

Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above.Conclusions In general,the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs,and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine,OS,inflammatory responses,and autophagy.These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.

Endoplasmic reticulum stress improved chicken tenderness,promoted apoptosis and autophagy during postmortem ageing

In this study,endoplasmic reticulum(ER)stress inducer tunicamycin(TM)and inhibitor 4-phenylbutyric acid(4-PBA)were used to treat postmortem chicken breast muscle to investigate changes in tenderness and effects on apoptosis and autophagy during 5 days ageing.TM-induced ER stress reduced shear force,enhanced myofibril fragmentation index(MFI),disrupted myofibril structure,increased desmin degradation,and activatedμ-calpain and caspase-12.In addition,TM-induced ER stress increased the expression of Bax,Bim,and cytochrome c,and decreased the expression of Bcl-x L.Furthermore,TM-induced ER stress improved the conversion of LC3I to LC3II,raised the expression of Beclin-1,and decreased the expression of p62,PI3K,and m TOR.The opposite results were observed after 4-PBA treatment.These results suggested that ER stress could improve chicken tenderness,promote apoptosis and autophagy during chicken postmortem ageing.

Re-identifying beef cattle using improved AlignedReID++

Accurate and continuous identification of individual cattle is crucial to precision farming in recent years.It is also the prerequisite to monitor the individual feed intake and feeding time of beef cattle at medium to long distances over different cameras.However,beef cattle can tend to frequently move and change their feeding position during feeding.Furthermore,the great variations in their head direction and complex environments(light,occlusion,and background)can also lead to some difficulties in the recognition,particularly for the bio-similarities among individual cattle.Among them,AlignedReID++model is characterized by both global and local information for image matching.In particular,the dynamically matching local information(DMLI)algorithm has been introduced into the local branch to automatically align the horizontal local information.In this research,the AlignedReID++model was utilized and improved to achieve the better performance in cattle re-identification(ReID).Initially,triplet attention(TA)modules were integrated into the BottleNecks of ResNet50 Backbone.The feature extraction was then enhanced through cross-dimensional interactions with the minimal computational overhead.Since the TA modules in AlignedReID++baseline model increased the model size and floating point operations(FLOPs)by 0.005 M and 0.05 G,the rank-1 accuracy and mean average precision(mAP)were improved by 1.0 percentage points and 2.94 percentage points,respectively.Specifically,the rank-1 accuracies were outperformed by 0.86 percentage points and 0.12 percentage points,respectively,compared with the convolution block attention module(CBAM)and efficient channel attention(ECA)modules,although 0.94 percentage points were lower than that of squeeze-and-excitation(SE)modules.The mAP metric values were exceeded by 0.22,0.86 and 0.12 percentage points,respectively,compared with the SE,CBAM,and ECA modules.Additionally,the Cross-Entropy Loss function was replaced with the CosFace Loss function in the global branch of baseline model.CosFace Loss and Hard Triplet Loss were jointly employed to train the baseline model for the better identification on the similar individuals.AlignedReID++with CosFace Loss was outperformed the baseline model by 0.24 and 0.92 percentage points in the rank-1 accuracy and mAP,respectively,whereas,AlignedReID++with ArcFace Loss was exceeded by 0.36 and 0.56 percentage points,respectively.The improved model with the TA modules and CosFace Loss was achieved in a rank-1 accuracy of 94.42%,rank-5 accuracy of 98.78%,rank-10 accuracy of 99.34%,mAP of 63.90%,FLOPs of 5.45 G,frames per second(FPS)of 5.64,and model size of 23.78 M.The rank-1 accuracies were exceeded by 1.84,4.72,0.76 and 5.36 percentage points,respectively,compared with the baseline model,part-based convolutional baseline(PCB),multiple granularity network(MGN),and relation-aware global attention(RGA),while the mAP metrics were surpassed 6.42,5.86,4.30 and 7.38 percentage points,respectively.Meanwhile,the rank-1 accuracy was 0.98 percentage points lower than TransReID,but the mAP metric was exceeded by 3.90 percentage points.Moreover,the FLOPs of improved model were only 0.05 G larger than that of baseline model,while smaller than those of PCB,MGN,RGA,and TransReID by 0.68,6.51,25.4,and 16.55 G,respectively.The model size of improved model was 23.78 M,which was smaller than those of the baseline model,PCB,MGN,RGA,and TransReID by 0.03,2.33,45.06,14.53 and 62.85 M,respectively.The inference speed of improved model on a CPU was lower than those of PCB,MGN,and baseline model,but higher than TransReID and RGA.The t-SNE feature embedding visualization demonstrated that the global and local features were achieve in the better intra-class compactness and inter-class variability.Therefore,the improved model can be expected to effectively re-identify the beef cattle in natural environments of breeding farm,in order to monitor the individual feed intake and feeding time.

Comparison of methods for deriving phenotypes from incomplete observation data with an application to age at puberty in dairy cattle

Background Many phenotypes in animal breeding are derived from incomplete measures,especially if they are challenging or expensive to measure precisely.Examples include time-dependent traits such as reproductive status,or lifespan.Incomplete measures for these traits result in phenotypes that are subject to left-,interval-and rightcensoring,where phenotypes are only known to fall below an upper bound,between a lower and upper bound,or above a lower bound respectively.Here we compare three methods for deriving phenotypes from incomplete data using age at first elevation(>1 ng/mL)in blood plasma progesterone(AGEP4),which generally coincides with onset of puberty,as an example trait.Methods We produced AGEP4 phenotypes from three blood samples collected at about 30-day intervals from approximately 5,000 Holstein–Friesian or Holstein–Friesian×Jersey cross-bred dairy heifers managed in 54 seasonal-calving,pasture-based herds in New Zealand.We used these actual data to simulate 7 different visit scenarios,increasing the extent of censoring by disregarding data from one or two of the three visits.Three methods for deriving phenotypes from these data were explored:1)ordinal categorical variables which were analysed using categorical threshold analysis;2)continuous variables,with a penalty of 31 d assigned to right-censored phenotypes;and 3)continuous variables,sampled from within a lower and upper bound using a data augmentation approach.Results Credibility intervals for heritability estimations overlapped across all methods and visit scenarios,but estimated heritabilities tended to be higher when left censoring was reduced.For sires with at least 5 daughters,the correlations between estimated breeding values(EBVs)from our three-visit scenario and each reduced data scenario varied by method,ranging from 0.65 to 0.95.The estimated breed effects also varied by method,but breed differences were smaller as phenotype censoring increased.Conclusion Our results indicate that using some methods,phenotypes derived from one observation per offspring for a time-dependent trait such as AGEP4 may provide comparable sire rankings to three observations per offspring.This has implications for the design of large-scale phenotyping initiatives where animal breeders aim to estimate variance parameters and estimated breeding values(EBVs)for phenotypes that are challenging to measure or prohibitively expensive.

Amlodipine inhibits the proliferation and migration of esophageal carcinoma cells through the induction of endoplasmic reticulum stress

BACKGROUND L-type calcium channels are the only protein channels sensitive to calcium channel blockers,and are expressed in various cancer types.The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue.Therefore,we hypothesized that amlodipine,a long-acting dihydropyridine L-type calcium channel blocker,may inhibit the occurrence and development of esophageal cancer(EC).AIM To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum(ER)stress.METHODS Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined.Subsequently,the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays.In vivo experiments were performed using murine xenograft model.To elucidate the underlying mechanisms,in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine.RESULTS The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues.Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose-and time-dependent manner.In vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice.Additionally,amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition(EMT).Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT.Moreover,amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein.The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of the ER stress response in amlodipine-induced apoptosis,EMT,and autophagy.Furthermore,blocking autophagy increases the ratio of apoptosis and migration.CONCLUSION Collectively,we demonstrate for the first time that amlodipine promotes apoptosis,induces autophagy,and inhibits migration through ER stress,thereby exerting anti-tumor effects in EC.

Cell division cyclin 25C knockdown inhibits hepatocellular carcinoma development by inducing endoplasmic reticulum stress

BACKGROUND Cell division cyclin 25C(CDC25C)is a protein that plays a critical role in the cell cycle,specifically in the transition from the G2 phase to the M phase.Recent research has shown that CDC25C could be a potential therapeutic target for cancers,particularly for hepatocellular carcinoma(HCC).However,the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely understood.AIM To explore the impact of CDC25C on cell proliferation and apoptosis,as well as its regulatory mechanisms in HCC development.METHODS Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences(LV-CDC25C shRNA)to knock down CDC25C.Subsequently,a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in vivo.Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays,respectively.The expression of endoplasmic reticulum(ER)stress-related molecules(glucose-regulated protein 78,X-box binding protein-1,and C/EBP homologous protein)was measured in both cells and subcutaneous xenografts using quantitative real-time PCR(qRT-PCR)and western blotting.Additionally,apoptosis was investigated using flow cytometry,qRT-PCR,and western blotting.RESULTS CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction.A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in mice.CDC25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response,ultimately promoting ER stress-induced apoptosis in HCC cells.CONCLUSION The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.

Celastrol activates caspase-3/GSDME-dependent pyroptosis in tumor cells by inducing endoplasmic reticulum stress Author links open overlay panel

Objective:To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved,specifically focusing on the role of the caspase-3/gasdermin E(GSDME)signaling pathway and the impact of endoplasmic reticulum(ER)stress and autophagy.Methods: Necrostatin-1(Nec-1),lactate dehydrogenase release(LDH)assay,and Hoechst/propidium iodide(PI)double staining were employed to validate the mode of cell death.Western blot was used to detect the cleavage of GSDME and the expression of light chain 3(LC3)and BIP.Results: Celastrol induced cell swelling with large bubbles,which is consistent with the pyroptotic phenotype.Moreover,treatment with celastrol induced GSDME cleavage,indicating the activation of GSDME-mediated pyroptosis.GSDME knockout via CRISPR/Cas9 blocked the pyroptotic morphology of celastrol in HeLa cells.In addition,cleavage of GSDME was attenuated by a specific caspase-3 inhibitor in celastrol-treated cells,suggesting that GSDME activation was induced by caspase-3.Mechanistically,celastrol induced endoplasmic reticulum(ER)stress and autophagy in HeLa cells,and other ER stress inducers produced effects consistent with those of celastrol.Conclusion: These findings suggest that celastrol triggers caspase-3/GSDME-dependent pyroptosis via activation of ER stress,which may shed light on the potential antitumor clinical applications of celastrol.

Protein Disulfide Isomerase and Its Potential Function on Endoplasmic Reticulum Quality Control in Diatom Phaeodactylum tricornutum

PDI is a molecular chaperone and plays an important role in Endoplasmic Reticulum quality control (ERQC).PDI participates in the refolding of the misfolded/unfolded proteins to maintain cellular homeostasis under differentstresses. However, bioinformatic characteristics and potential functions of PDIs in diatom Phaeodactylumtricornutum (Pt) are still unknown so far. Hence, the genome-wide characteristics of PtPDI proteins in P. tricornutumwere first studied via bioinformatic and transcriptomic methods. 42 PtPDI genes were identified from thegenome of P. tricornutum. The motif, protein structure, classification, number of introns, phylogenetic relationship,and the expression level of 42 PtPDI genes under the tunicamycin stress were analyzed. A pair of tandemduplicated genes (PtPDI15 and PtPDI18) was observed in P. tricornutum. The 42 PtPDIs with different genecharacteristics were divided into three independent clades, indicating different evolutional relationships and functionsof these PtPDIs. The 14 up-regulated PtPDI genes under the tunicamycin treatment might have a positiveeffect on the ER quality control of the unfolded/misfolded proteins, while the 7 down-regulated PtPDIs mightnegatively affect the ERQC. The characteristics of all 42 PtPDIs and their proposed working model here providea comprehensive understanding of the PtPDIs gene family. The differential expression of 21 PtPDIs will be usefulfor further functional study in the ERQC.

Progress of mitochondrial and endoplasmic reticulum-associated signaling and its regulation of chronic liver disease by Chinese medicine

The endoplasmic reticulum(ER)is connected to mitochondria through mitochondria-associated ER membranes(MAMs).MAMs provide a framework for crosstalk between the ER and mitochondria,playing a crucial role in regulating cellular calcium balance,lipid metabolism,and cell death.Dysregulation of MAMs is involved in the development of chronic liver disease(CLD).In CLD,changes in MAMs structure and function occur due to factors such as cellular stress,inflammation,and oxidative stress,leading to abnormal interactions between mitochondria and the ER,resulting in liver cell injury,fibrosis,and impaired liver function.Traditional Chinese medicine has shown some research progress in regulating MAMs signaling and treating CLD.This paper reviews the literature on the association between mitochondria and the ER,as well as the intervention of traditional Chinese medicine in regulating CLD.

SIRT1 inhibits apoptosis of human lens epithelial cells through suppressing endoplasmic reticulum stress in vitro and in vivo

AIM:To explore the effect of silent information regulator factor 2-related enzyme 1(SIRT1)on modulating apoptosis of human lens epithelial cells(HLECs)and alleviating lens opacification of rats through suppressing endoplasmic reticulum(ER)stress.METHODS:HLECs(SRA01/04)were treated with varying concentrations of tunicamycin(TM)for 24h,and the expression of SIRT1 and C/EBP homologous protein(CHOP)was assessed using real-time quantitative polymerase chain reaction(RT-PCR),Western blotting,and immunofluorescence.Cell morphology and proliferation was evaluated using an inverted microscope and cell counting kit-8(CCK-8)assay,respectively.In the SRA01/04 cell apoptosis model,which underwent siRNA transfection for SIRT1 knockdown and SRT1720 treatment for its activation,the expression levels of SIRT1,CHOP,glucose regulated protein 78(GRP78),and activating transcription factor 4(ATF4)were examined.The potential reversal of SIRT1 knockdown effects by 4-phenyl butyric acid(4-PBA;an ER stress inhibitor)was investigated.In vivo,age-related cataract(ARC)rat models were induced by sodium selenite injection,and the protective role of SIRT1,activated by SRT1720 intraperitoneal injections,was evaluated through morphology observation,hematoxylin and eosin(H&E)staining,Western blotting,and RT-PCR.RESULTS:SIRT1 expression was downregulated in TMinduced SRA01/04 cells.Besides,in SRA01/04 cells,both cell apoptosis and CHOP expression increased with the rising doses of TM.ER stress was stimulated by TM,as evidenced by the increased GRP78 and ATF4 in the SRA01/04 cell apoptosis model.Inhibition of SIRT1 by siRNA knockdown increased ER stress activation,whereas SRT1720 treatment had opposite results.4-PBA partly reverse the adverse effect of SIRT1 knockdown on apoptosis.In vivo,SRT1720 attenuated the lens opacification and weakened the ER stress activation in ARC rat models.CONCLUSION:SIRT1 plays a protective role against TM-induced apoptosis in HLECs and slows the progression of cataract in rats by inhibiting ER stress.These findings suggest a novel strategy for cataract treatment focused on targeting ER stress,highlighting the therapeutic potential of SIRT1 modulation in ARC development.

Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

Cattle Production and Lumpy Skin Disease of Smallholder Farmers in Svay Rieng Province

The cattle production in Romeas Haek district,Svay Rieng province,was developed remarkably,since there were some households raising cattle in large number,more than 20 heads.The grazing method of cattle was tethering and free grassing in the commune grass,since the natural grass and rice straw were the main source of cattle feed,however some of them supplemented their cattle with crop-byproducts,planting grass or concentrated feed.For the majority,BCS(Body Condition Scoring)of the cattle in those areas was 3 accounting for 52%-73.33%,but it was found the thin cattle has low BCS of 2 accounting for 11.11%to 40.00%and also fat cattle has BCS of 4 up to 27.78%.However,the average BCS varied with village which ranged from 2.68 to 3.17,but is not different in term of commune and sex of cattle.Besides facing with shortage of feed,the experience with diseases was also another concern,since 85.71%to 95.83%of the households faced this problem last year.Among the clinical signs found,lumpy skin was 100%,i.e.no one escaped from this problem,thus making them aware of vaccinating their cattle against some diseases such as FMD(Foot and Mouth Disease),HS(Hemorrhagic Septicemia)and LSD(Lumpy Skin Disease),but mostly vaccination was used against FMD.Because the LSD has occurred in these areas since 2020,then the seroprevalence was found in high positive up to 72.62%by Enzyme-Linked Immunosorbent Assay(ELISA)test.This positive rate was also varying by villages,ranging from 53.3%to 94.44%.But there was no association between positive cattle with commune,BCS,sex and age of cattle.In conclusion,the cattle production in Romeas Haek district,Svay Rieng province had developed markedly,however the shortage of feed and disease occurrence are the main challenges for farmer cattle producers,especially LSD outbreak last year.However,most of the farmers have been aware of the benefit of vaccination and had vaccinated their cattle against those main disease,such as FMD,HS and LSD.