CX3 chemokine receptor 1 deficiency leads to reduced dendritic complexity and delayed maturation of newborn neurons in the adult mouse hippocampus

Previous studies have shown that microglia impact the proliferation and differentiation of neu- rons during hippocampal neurogenesis via the fractalkine/CX3 chemokine receptor i （CX3CRI） signaling pathway. However, whether microglia can influence the maturation and dendritic growth of newborn neurons during hippocampal neurogenesis remains unclear. In the present study, we found that the number of doublecortin-positive cells in the hippocampus was decreased, and the dendritic length and number of intersections in newborn neurons in the hippocampus were reduced in transgenic adult mice with CX3CR1 deficiency （CX3CRl^GFP/GFe）. Furthermore, after experimental seizures were induced with kainic acid in these CX3CRl-deficient mice, the expression of c-fos, a marker of neuronal activity, was reduced compared with wild-type mice. Collectively, the experimental findings indicate that the functional maturation of newborn neu- rons during hippocampal neurogenesis in adult mice is delayed by CX3CR1 deficiency.

Mouse KL2 is a unique MTSE involved in chromosome-based spindle organization and regulated by multiple kinases during female meiosis

Microtubule-severing enzymes(MTSEs)play important roles in mitosis and meiosis of the primitive organisms.However,their roles in mammalian female meiosis,which accounts for over 80%of gamete-originated human reproductive diseases,remain unexplored.In the current study,we reported that katanin-like 2(KL2)was the only MTSE concentrating at chromosomes.Furthermore,the knockdown of KL2 significantly reduced the chromosome-based increase in the microtubule(MT)polymer,increased aberrant kinetochore-MT(K-MT)attachment,delayed meiosis,and severely affected normal fertility.We demonstrated that the inhibition of aurora B,a key kinase for correcting aberrant K-MT attachment,significantly eliminated KL2 expression from chromosomes.Additionally,KL2 interacted with phosphorylated eukaryotic elongation factor-2 kinase,and they competed for chromosome binding.Phosphorylated KL2 was also localized at spindle poles,with its phosphorylation regulated by extracellular signal-regulated kinase 1/2.In summary,the current study reveals a novel function of MTSEs in mammalian female meiosis and demonstrates that multiple kinases coordinate to regulate the levels of KL2 at chromosomes.

Draft of an Anthropometric Reference System for Full-Term Cameroonian Newborns: Prospective Study with Analytical Aim in the Maternity Wards of Douala

Introduction: Anthropometry applied to newborns is a reliable indicator of the quality of fetal growth. The latter is influenced by genetic, racial and nutritional factors varying from one population to another, explaining why a standard cannot be applied to all populations. Research question: should the Caucasian frame of reference be dogmatically applied in our African context? Multicenter studies are therefore necessary;hence the interest of this work, the main objective of which was to describe the anthropometric profile of full-term newborns in the city of Douala. Methodology: We carried out a cross-sectional study with an analytical aim and prospective data collection in the maternity wards of the Douala General Hospital, Laquintinie Hospital, District hospitals of Deido, Nylon and Bonassama over a period of 4 months (January to April 2020). We were interested in any newborn, born alive, vaginally or by cesarean section, seen in the first 24 hours from a full-term single-fetal pregnancy whose mother had given consent. We excluded newborns whose term was unclear and those with congenital malformations or signs of embryo-foetopathy. Data collection was done using structured and pre-tested survey sheets. The study variables were obstetric and anthropometric. Statistical analyzes were carried out with CS Pro 7.3 and SPSS version 25.0 software. The Student, Chi-square and Fischer tests were used to compare the means of the variables, the percentages with a significance threshold P value Results: During the study period, 305 full-term newborns were included, divided into 172 boys and 133 girls. The average anthropometric parameters of the full-term newborn in the city of Douala were: average weight: 3305 grams, average height: 49.8 centimeters, average head circumference: 34.6 centimeters, average upper arm circumference: 11.3 centimeters, circumference average thoracic: 32.8 centimeters. The percentile distribution showed a 10th percentile at 2656 grams and a 90th percentile at 3966 grams for weight defining the limits for small-for-gestational-age neonates and macrosomes. Conclusion: The anthropometric data of the full-term newborn in the city of Douala were: an average weight of 3305.4 grams, an average height of 49.8 centimeters, an average head circumference of 34.2 centimeters, an average upper arm circumference of 11.3 centimeters, and an average thoracic circumference of 32.8 centimeters with higher valuesin male newborns.

Role of cancer stem cell ecosystem on breast cancer metastasis and related mouse models

Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and differentiation.Studies have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast cancer.The tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ability.Hence,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer metastasis.In this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory mechanisms.Furthermore,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during metastasis.Overall,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.

A Comparison between Late Preterm and Term Infants with Respiratory Distress Syndrome, Early-Onset Sepsis, and Neonatal Jaundice in Ecuadorian Newborns

Background: To examine the differences in prevalence of respiratory distress syndrome, early-onset sepsis and jaundice, between late preterm infants versus term infants in Ecuadorian newborns. Methods: Study design: Epidemiological, observational, and cross-sectional, with two cohorts of patients. Settings: IESS Quito Sur Hospital at Quito, Ecuador, from February to April of 2020. Participants: This study included 204 newborns, 102 preterm infants, 102 term infants. Results: There are significant differences between late preterm infants and term infants, with a p-value of 0.000 in the prevalence of early sepsis, 70.59% vs. 35.29%. In respiratory distress syndrome between late and term premature infants, significant differences were observed with a p-value of 0.000, the proportion being 55.58% vs. 24.51% respectively. The prevalence of jaundice is higher in term infants with a p value of 0.002, 72.55%, versus 51.96% in late preterm infants, and the mean value of bilirubins in mg/dL was higher in term infants 14.32 versus 12.33 in late preterm infants;this difference is statistically significant with a p value of 0.004. Admission to the NICU is more frequent in late preterm infants with a p-value of 0.000, being 42.16% for late preterm infants vs. 7.84% in term infants;the mean of the hospital days with p-value 0.005, was higher in late preterm infants 4.97 days vs. 3.55 days for term newborns. Conclusion: Due to the conditions of their immaturity, late preterm infants are 2.86 times more likely to present early sepsis than full-term newborns. It is shown that late preterm infants are 2.69 times more likely to have respiratory distress syndrome compared to term infants, therefore, late preterm infants have a longer hospital stay of 4.97 days versus 3.55 days in term infants. Jaundice and mean bilirubin levels are higher in term infants due to blood group incompatibility and insufficient breastfeeding.

Comparison of immune responses and intestinal flora in epicutaneously sensitized BALB/c or C57BL/6 mouse models of food allergy

Cutaneous exposure to food allergens through a disrupted skin barrier is recognized as an important cause of food allergy,and the cutaneous sensitized mouse model has been established to investigate relevant allergic disorders.However,the role of different genetic backgrounds of mice on immune responses to food allergens upon epicutaneous sensitization is largely unknown.In this study,two strains of mice,i.e.,the BALB/c and C57BL/6 mice,were epicutaneously sensitized with ovalbumin on atopic dermatitis(AD)-like skin lesions,followed by intragastric challenge to induce IgE-mediated food allergy.Allergic outcomes were measured as clinical signs,specific antibodies and cytokines,and immune cell subpopulations,as well as changes in intestinal barrier function and gut microbiota.Results showed that both strains of mice exhibited typical food-allergic symptoms with a Th2-skewed response.The C57BL/6 mice,rather than the BALB/c mice,were fitter for establishing an epicutaneously sensitized model of food allergy since a stronger Th2-biased response and severer disruptions in the intestinal barrier and gut homeostasis were observed.This study provides knowledge for selecting an appropriate mouse model to study food-allergic responses associated with AD-like skin lesions and highlights the role of genetic variations in the immune mechanism underlying pathogenesis of food allergy.

Assessment of Awareness and Understanding of Hemolytic Disease of the Fetus and Newborn in the Beninese Population

Background: Hemolytic Disease of the Fetus and Newborn (HDFN) arises from blood group incompatibility, especially the RhD antigen. In Benin, systematic ABO RhD blood grouping is poorly understood by many midwives and nurses. Nearly one in ten women risk having children with HDFN. This study aimed to determine the level of knowledge of the Beninese population on HDFN. Methods: Data were collected from June 2023 to March 2024. Participants completed a Kobotoolbox questionnaire on WhatsApp, with in-person assistance for illiterate participants. The study involved 521 participants from across Benin. Data were analyzed using SigmaPlot version 14.0. Results: Among the 521 participants, 298 were women (57.20%) aged 18 to 77 years. The majority (40.69%) were aged 26 - 35. Over a third (35.51%) did not know their RhD blood group. Most (59.12%) were unaware of the risks for RhD discordant couples. Among those with a partner, 25.16% were in at-risk couples for HDFN, and over half (59.12%) were unaware of this risk. There was no significant association between being in a high-risk union and knowledge of the risk or education level. Conclusion: Only 40.88% of the Beninese population are aware of HDFN, indicating a low level of knowledge.

Establishment and Evaluation of a Mouse Model of Allergic Rhinitis

[Objectives]To explore a new method for induction of allergic rhinitis in mice,and compare and evaluate it with common modeling methods.[Methods]36 mice were randomly divided into the control group,blank group and experimental group,and there were 12 mice in each group.The mice in the control group were conventionally induced.That is,the mice were first injected intraperitoneally with the mixture composed of OVA 50μg,[Al(OH)3]5 mg and 1ml of normal saline once every other day,and then since the 15 th d,20μL of 5%OVA solution was dropped into each nasal cavity once a day,which lasted for 7 d.The blank group was treated with the same amount of normal saline according to the control group,and received intraperitoneal injection and bilateral nasal drip respectively.In the experimental group,mice were first given intraperitoneal injection of the mixture composed of ovalbumin(OVA)75μg,aluminum hydroxide gel[Al(OH)3]8 mg and normal saline 1.5 mL for basic sensitization.On the 26 th d,20μL of 3%OVA solution was dropped into each nasal cavity once a day,which lasted for 10 d.The number of sneezes,the number of nose scratching,the amount of nasal discharge,and the activity of mice in each group were observed,and the behavior of allergic reaction was scored.Meanwhile,the number of eosinophils in the nasal discharge of mice and the IgE content in serum were measured.[Results]The score of nasal stimulation symptoms,the number of eosinophils and serum IgE level of mice in the control group and the experimental group were higher than those in the blank group(P<0.05),and there was no statistical significance between the two groups in the three indicators(P>0.05).[Conclusions]The modeling method was more suitable for the development of allergic rhinitis patients condition,and reduced the probability of death of mice due to modeling,and simplified the experimental operation.

Diagnostic significance of serum levels of serum amyloid A,procalcitonin,and high-mobility group box 1 in identifying necrotising enterocolitis in newborns

BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emerged as potential biomarkers for NEC due to their roles in inflammatory response,tissue damage,and immune regulation.AIM To evaluate the diagnostic value of SAA,PCT,and HMGB1 in the context of NEC in newborns.METHODS The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital.Clinical,radiological,and laboratory findings,including serum SAA,PCT,and HMGB1 Levels,were collected,and specific detection methods were used.The diagnostic value of the biomarkers was evaluated through statistical analysis,which was performed using chi-square test,t-test,correlation analysis,and receiver operating characteristic(ROC)analysis.RESULTS The study demonstrated significantly elevated levels of serum SAA,PCT,and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls.The correlation analysis indicated strong positive correlations among serum SAA,PCT,and HMGB1 Levels and the presence of NEC.ROC analysis revealed promising sensitivity and specificity for serum SAA,PCT,and HMGB1 Levels as potential diagnostic markers.The combined model of the three biomarkers demonstrating an extremely high area under the curve(0.908).CONCLUSION The diagnostic value of serum SAA,PCT,and HMGB1 Levels in NEC was highlighted.These biomarkers potentially improve the early detection,risk stratification,and clinical management of critical conditions.The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.

Expression levels of K_(ATP)channel subunits and morphological changes in the mouse liver after exposure to radiation

BACKGROUND ATP sensitive K+(K_(ATP))channels are ubiquitously distributed in various of cells and tissues,including the liver.They play a role in the pathogenesis of myocardial and liver ischemia.AIM To evaluate the radiation-induced changes in the expression of K_(ATP)channel subunits in the mouse liver to understand the potential role of K_(ATP)channels in radiation injury.METHODS Adult C57BL/6 mice were randomly exposed toγ-rays at 0 Gy(control,n=2),0.2 Gy(n=6),1 Gy(n=6),or 5 Gy(n=6).The livers were removed 3 and 24 h after radiation exposure.Hematoxylin and eosin staining was used for morphological observation;immunohistochemical staining was applied to determine the expression of K_(ATP)channel subunits in the liver tissue.RESULTS Compared with the control group,the livers exposed to 0.2 Gyγ-ray showed an initial increase in the expression of Kir6.1 at 3 h,followed by recovery at 24 h after exposure.Exposure to a high dose of 5.0 Gy resulted in decreased expression of Kir6.1 and increased expression of SUR2B at 24 h.However,the expression of Kir6.2,SUR1,or SUR2A had no remarkable changes at 3 and 24 h after exposure to any of these doses.CONCLUSION The expression levels of Kir6.1 and SUR2B in mouse liver changed differently in response to different radiation doses,suggesting a potential role for them in radiation-induced liver injury.

Effects of Polygala fallax Hemsl Water Extract on a Mouse Model of Gastric Motility Disorders

[Objectives]To explore the effects of Polygona fallax Hemsl water extract on gastrointestinal motility in normal mice and gastric motility disorder model mice and approximate mechanism.[Methods]Using normal mice and mice with gastric motility disorders(modeled with atropine),the effects of different mass concentration groups of P.fallax Hemsl water extract(0.125,0.250,0.500 g/mL)and domperidone groups on gastric residual rate,small intestine propulsion rate,serum motilin(MLT),vasoactive intestinal peptide(VIP),and tissue morphology were studied.[Results]There was a highly significant difference(P<0.01)in the small intestine propulsion rate of liquid in normal mice among the different concentration groups of P.fallax Hemsl water extract compared to the blank group.The small intestine propulsion rate and gastric residue rate of semi-solid paste were statistically significant compared to the blank group(P<0.05).Among them,there was a highly significant difference between the high concentration group(67.75%±7.65%,46.5%±10.62%)and the medium concentration group(60.90%±5.87%,59.27%±7.82%)(P<0.01).There was statistical significance in normal mouse serum MLT content in the high concentration group(P<0.05).There was no effect on serum VIP levels in normal mice;no effect on the morphology of stomach and intestinal tissues of normal mice.The small intestine propulsion rate and gastric residue rate of liquid and semi-solid paste in mice with gastric motility disorders were statistically significant compared to the atropine group,with extremely significant differences(P<0.01).[Conclusions]P.fallax Hemsl water extract has a promoting effect on gastrointestinal motility.One of the specific mechanisms by which P.fallax Hemsl promotes gastrointestinal motility in normal mice may be related to the content of MLT in mouse serum.The mechanism of action in atropine induced gastric paresis mice may be related to the reactivation of M receptors,and the action mechanism of P.fallax Hemsl does not change the original histological basis.It can be inferred that P.fallax Hemsl water extract has a synergistic effect on promoting gastrointestinal motility through other mechanisms,but it is not fully understood and further in-depth research is needed.

Ethanol changes Nestin-promoter induced neural stem cells to disturb newborn dendritic spine remodeling in the hippocampus of mice

Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal neurogenesis.In this study,we applied in vivo fluorescent tracing using NestinCreERT2::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells(NSCs)and dendritic spine formation of newborn neurons in the subgranular zone of the dentate gyrus.We found abnormal orientation of tamoxifen-induced tdTomato+(tdTom^(+))NSCs in adult mice 2 months after treatment with EtOH(5.0 g/kg,i.p.)for 7 consecutive days.EtOH markedly inhibited tdTom^(+)NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to adulthood.EtOH(100 mM)also significantly inhibited the proliferation to 39.2%and differentiation of primary NSCs in vitro.Adult mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus,which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycinenhancer of zeste homolog 2 pathway.In vivo tracing revealed that EtOH induced abnormal orientation of tdTom+NSCs and spatial misposition defects of newborn neurons,thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.

Morbidity and Mortality of Newborns in a Context of Limited Resources in Tombouctou, Mali

Introduction: Worldwide, 2.3 million children died in the first 20 days after birth in 2022, according to the WHO. In Mali, according to the sixth Demographic and Health Survey, the neonatal mortality rate was estimated at 33% live births in 2018. The Timbuktu region had the highest neonatal mortality rate in the country with 44%. The objective of this work was to study the causes of neonatal morbidity and mortality and related factors in the paediatrics department of Timbuktu hospital. Materials and method: This was a descriptive, cross-sectional study conducted from 1 January to 31 December 2023 in the neonatology unit of the paediatrics department of Timbuktu hospital, including all newborns admitted to hospital. Results: Our study took place over 12 months, during which 618 admissions were made to the paediatric ward, including 244 newborns, i.e. 39.48%. The majority of newborns (86.5%) were admitted in the first week of life. The mean age was 3 days, with a sex ratio of 1.1 for males. Weight under 2500 g was 54.1% for an average weight of 2372 g. The main mode of admission was transfer from the hospital maternity unit (62%). The main reasons for admission were acute foetal distress (27.9%) and prematurity (26.2%). The average age of the mothers was 24, with extremes of 15 and 49. The mothers were housewives (87.3%), uneducated and primiparous (59% and 36.5% respectively);only 40.2% had made more than 3 antenatal care visits. Newborns born by vaginal delivery accounted for 80.7% and those born by caesarean section for 19.3%. The risk of infection was present in 52.5% of cases. The three leading causes of hospitalisation were birth asphyxia (40.2%), neonatal infection (32.4%) and prematurity (25%). The mortality rate was 21.7%. The main causes of death were prematurity (39.6%), birth asphyxia (32.1%) and neonatal infection (24.5%). Conclusion: Neonatal morbidity and mortality remain a concern in Timbuktu. Despite the unfavourable security situation, morbidity and mortality indicators are close to those in some hospitals in Mali. The correct application of Essential Newborn Care and antenatal care remains a major challenge for the hospital and the Timbuktu region.

Universal newborn hearing screening program in Saudi Arabia: Current insight

Newborn hearing screening(NHS) programs are essential to identify hearing loss early in life and to improve outcomes in children. In Saudi Arabia, the national NHS program has been operational since 2016;however, few studies have evaluated its status, and none have covered all provinces across the country. This cross-sectional retrospective study provides an overview of the program's status across all provinces, focusing on screening coverage rates, referral/fail rates, and follow-up procedures. In 2021, 199,034 newborns were screened, with a coverage rate of 92.6% and an overall referral/fail rate of 1.87%. These performance measures provide a foundation for future progress and improvements. This study highlights the importance of ongoing efforts to enhance the program's effectiveness and sustainability.

A Comparison of Turnaround-Times for Two Popular Specimen Types Used for Newborn Toxicology: Meconium and Umbilical Cord Tissue

Background: Prenatal exposure to illicit substances is responsible for several long-term negative health consequences. It is critical for healthcare professionals to know the extent and scope of prenatal substance exposure in their cases. Several studies exist with mixed results comparing the effectiveness of umbilical cord tissue (UCT) and meconium (MEC) as toxicology specimen types. The specific aim of this study is to compare the use of UCT and MEC regarding the time interval between the birth of the neonate, receipt of the specimen at the laboratory, and the hospital’s receipt of the final toxicology report. Method: The study queried de-identified results of 5358 consecutive UCT and 706 MEC from our laboratory. Results: The mean time from birth to receipt of the specimen at the laboratory for MEC and UCT was 4.5 days ± 2.9 days and 2.8 days ± 1.9 days, respectively. The mean time from birth to final report for MEC was 6.9 days ± 3.8 days, 5.7 days ± 3.3 days, and 8.4 days ± 3.8 days for all MEC specimens, negative MEC, and positive MEC, respectively. The mean time from birth to final report for UCT was 4.3 days ± 2.4 days, 3.5 days ± 2.2 days, and 5.4 days ± 2.2 days for all UCT, negative UCT and positive UCT, respectively. Discussion/Conclusion: Receipt of drug test results of the neonate prior to release from the hospital is critical. This study shows that UCT offers an advantage when results are needed quickly to make informed decisions about the health and well-being of newborns.

Balloon dilation of congenital perforated duodenal web in newborns: Evaluation of short and long-term results

BACKGROUND Incomplete congenital duodenal obstruction(ICDO)is caused by a congenitally perforated duodenal web(CPDW).Currently,only six cases of balloon dilatation of the PDW in newborns have been described.AIM To present our experience of balloon dilatation of a perforated duodenal memb-rane in newborns with ICDO.METHODS Five newborns who underwent balloon dilatation of the CPDW along a prein-stalled guidewire between 2021 and 2023 were included.Nineteen newborns diagnosed with ICDO who underwent laparotomy were included in the control group.RESULTS In all cases,good anatomical and clinical results were obtained.In three cases,a follow-up study was conducted after 1 year.The average time to start enteral feeding per os was significantly earlier in the study group(4.4 d)than in the laparotomic group(21.2 days;P<0.0001).The time spent by patients in the intensive care unit and hospital after balloon dilatation was also significantly shorter.We determined the selection criteria for possible and effective CPDW balloon dilatation in newborns as follows:(1)Presence of dynamic radiographic signs of the passage of a radiopaque substance beyond the zone of narrowing or radiographic signs of pneumatisation of the duodenum and small bowel distal to the web;(2)presence of endoscopic signs of CPDW;(3)successful cannulation with a guidewire performed parallel to the endoscope,with holes in the congenital duodenal web;and(4)successful positioning of the balloon performed along a freestanding guidewire on the web.CONCLUSION Strictly following selection criteria for newborns with ICDO caused by CPDW ensures that endoscopic balloon dilatation using a pre-installed guidewire is safe and effective and shows good 1-year follow-up results.

Mouse models of epithelial ovarian cancer for preclinical studies

Epithelial ovarian cancer(EOC) is the leading cause of gynecological cancer-related mortality in the developed world. EOC is a heterogeneous disease represented by several histological and molecular subtypes. Therefore, exploration of relevant preclinical animal models that consider the heterogenic nature of EOC is of great importance for the development of novel therapeutic strategies that can be translated clinically to combat this devastating disease. In this review, we discuss recent progress in the development of preclinical mouse models for EOC study as well as their advantages and limitations.

MicroRNAs in mouse and rat models of experimental epilepsy and potential therapeutic targets

Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.

Anti-infection effects of heparin on SARS-CoV-2 in a diabetic mouse model

Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.

Designing and generating a mouse model:frequently asked questions

Genetically engineered mouse(GEM)models are commonly used in biomedical research.Generating GEMs involve complex set of experimental procedures requiring sophisticated equipment and highly skilled technical staff.Because of these reasons,most research institutes set up centralized core facilities where custom GEMs are created for research groups.Researchers,on the other hand,when they begin thinking about generating GEMs for their research,several questions arise in their minds.For example,what type of model(s)would be best useful for my research,how do I design them,what are the latest technologies and tools available for developing my model(s),and finally how to breed GEMs in my research.As there are several considerations and options in mouse designs,and as it is an expensive and time-consuming endeavor,careful planning upfront can ensure the highest chance of success.In this article,we provide brief answers to several frequently asked questions that arise when researchers begin thinking about generating mouse model(s)for their work.