Brain organoids encompass a large collection of in vitro stem cell–derived 3D culture systems that aim to recapitulate multiple aspects of in vivo brain development and function.First,this review provides a brief int...Brain organoids encompass a large collection of in vitro stem cell–derived 3D culture systems that aim to recapitulate multiple aspects of in vivo brain development and function.First,this review provides a brief introduction to the current state-of-the-art for neuroectoderm brain organoid development,emphasizing their biggest advantages in comparison with classical two-dimensional cell cultures and animal models.However,despite their usefulness for developmental studies,a major limitation for most brain organoid models is the absence of contributing cell types from endodermal and mesodermal origin.As such,current research is highly investing towards the incorporation of a functional vasculature and the microglial immune component.In this review,we will specifically focus on the development of immune-competent brain organoids.By summarizing the different approaches applied to incorporate microglia,it is highlighted that immune-competent brain organoids are not only important for studying neuronal network formation,but also offer a clear future as a new tool to study inflammatory responses in vitro in 3D in a brainlike environment.Therefore,our main focus here is to provide a comprehensive overview of assays to measure microglial phenotype and function within brain organoids,with an outlook on how these findings could better understand neuronal network development or restoration,as well as the influence of physical stress on microglia-containing brain organoids.Finally,we would like to stress that even though the development of immune-competent brain organoids has largely evolved over the past decade,their full potential as a pre-clinical tool to study novel therapeutic approaches to halt or reduce inflammation-mediated neurodegeneration still needs to be explored and validated.展开更多
Developmental instability(DI)is a phenomenon whereby organisms are unable to buffer developmental disturbances,resulting in asymmetricvariation of paired traits.Previous research has demonstrated a negative relationsh...Developmental instability(DI)is a phenomenon whereby organisms are unable to buffer developmental disturbances,resulting in asymmetricvariation of paired traits.Previous research has demonstrated a negative relationship between DI,measured as forearm asymmetry,and survivalin the bat Carollia perspicillata.This study aims to test the hypothesis that individuals with higher DI exhibit a lower immune response.We measured a delayed-type hypersensitivity to the antigen phytohemagglutinin(PHA)on 74 males and 65 females of C.perspicillata before and after thebreeding season(BS).Linear models were used to predict the immunological response based on body mass(BM),forearm asymmetry,sex,BS,and testicle length.The best-ftting model accounted for 29% of the variation in immune response and included asymmetry,BM,sex,and BS aspredictors.The immune response was negatively associated with asymmetry and testicle length in males but positively related to asymmetryin females.Both sexes showed a reduced immune response in the late BS.Additionally,the association between immune response and BMchanged direction seasonally,with heavier individuals showing weaker responses early in the BS and stronger responses later.Individual variation in male immunity was predicted by individual attributes,whereas variation in immune response in females was mostly seasonal.Our resultssupport the link between DI,survival,and immune response in short-tailed bats,and suggest that the immunological component measured bythe PHA response may be under fner selection in males due to its stronger correlation with individual traits.展开更多
Background Enterotoxigenic Escherichia coli(E.coli)is a threat to humans and animals that causes intestinal dis-orders.Antimicrobial resistance has urged alternatives,including Lactobacillus postbiotics,to mitigate th...Background Enterotoxigenic Escherichia coli(E.coli)is a threat to humans and animals that causes intestinal dis-orders.Antimicrobial resistance has urged alternatives,including Lactobacillus postbiotics,to mitigate the effects of enterotoxigenic E.coli.Methods Forty-eight newly weaned pigs were allotted to NC:no challenge/no supplement;PC:F18^(+)E.coli chal-lenge/no supplement;ATB:F18^(+)E.coli challenge/bacitracin;and LPB:F18^(+)E.coli challenge/postbiotics and fed diets for 28 d.On d 7,pigs were orally inoculated withF18^(+)E.coli.At d 28,the mucosa-associated microbiota,immune and oxidative stress status,intestinal morphology,the gene expression of pattern recognition receptors(PRR),and intestinal barrier function were measured.Data were analyzed using the MIXED procedure in SAS 9.4.Results PC increased(P<0.05)Helicobacter mastomyrinus whereas reduced(P<0.05)Prevotella copri and P.ster-corea compared to NC.The LPB increased(P<0.05)P.stercorea and Dialister succinatiphilus compared with PC.The ATB increased(P<0.05)Propionibacterium acnes,Corynebacterium glutamicum,and Sphingomonas pseudosanguinis compared to PC.The PC tended to reduce(P=0.054)PGLYRP4 and increased(P<0.05)TLR4,CD14,MDA,and crypt cell proliferation compared with NC.The ATB reduced(P<0.05)NOD1 compared with PC.The LPB increased(P<0.05)PGLYRP4,and interferon-γand reduced(P<0.05)NOD1 compared with PC.The ATB and LPB reduced(P<0.05)TNF-αand MDA compared with PC.Conclusions TheF18^(+)E.coli challenge compromised intestinal health.Bacitracin increased beneficial bacteria show-ing a trend towards increasing the intestinal barrier function,possibly by reducing the expression of PRR genes.Lac-tobacillus postbiotics enhanced the immunocompetence of nursery pigs by increasing the expression of interferon-γand PGLYRP4,and by reducing TLR4,NOD1,and CD14.展开更多
BACKGROUND Histoplasmosis is a rare infectious condition with mainly pulmonary involvement which is generally self-limiting in immunocompetent individuals.Its manifestation varies and lacks specificity.This study repo...BACKGROUND Histoplasmosis is a rare infectious condition with mainly pulmonary involvement which is generally self-limiting in immunocompetent individuals.Its manifestation varies and lacks specificity.This study reports a case of primary disseminated liver histoplasmosis in a normal host presenting as liver failure cured by liver transplantation and voriconazole.CASE SUMMARY A 43-year-old Chinese man with intermittent fever,malaise,jaundice and extreme hepatomegaly for more than 40 days was admitted to the Second Xiang-ya Hospital.The patient was immunocompetent and lacked a definitive history of exposure.His condition deteriorated to liver failure,and he promptly underwent liver transplantation to ensure survival.One year later,the patient presented with severe gastrointestinal symptoms,including fever,abdominal pain,and diarrhea.Subsequently,tissue samples acquired via gastrointestinal endoscopy were subjected to pathological examination and next-generation sequencing analysis.Through a comprehensive amalgamation of clinical presentation,biopsy pathology,and next-generation sequencing analysis,the patient was ultimately diagnosed with disseminated hepatic histoplasmosis.The patient achieved complete recovery after 6 months of voriconazole treatment.CONCLUSION In patients with chronic-hepatitis-B having atypical symptoms,histoplasmosis can be a differential diagnosis.Voriconazole is effective in treating histoplasmosis.展开更多
We examined the case report written by Ke et al,describing a rare clinical case.In this editorial,we would like to emphasize the differential diagnosis of rectal masses through a rare case.We describe a case of amebom...We examined the case report written by Ke et al,describing a rare clinical case.In this editorial,we would like to emphasize the differential diagnosis of rectal masses through a rare case.We describe a case of ameboma,which manifested itself as a mass in the rectum in terms of imaging and rectoscopic features,in an immunocompetent patient who had complaints of constipation and rectal bleeding for weeks.The initial diagnosis suggested malignancy due to imaging and rectoscopic features,but the pathology report reported it as amoebiasis.After ten days of metronidazole and oral amebicide(diloxanide furoate)treatment,the patient’s symptoms and radiological findings were successfully regressed.展开更多
Human herpesvirus 6(HHV-6)is a common childhood infection but rarely causes severe complications.In immunocompetent children,conditions such as febrile convulsions and roseola infantum are typical,with occasional seve...Human herpesvirus 6(HHV-6)is a common childhood infection but rarely causes severe complications.In immunocompetent children,conditions such as febrile convulsions and roseola infantum are typical,with occasional severe manifestations like meningoencephalitis and myocarditis.展开更多
Gastric cancer(GC)is a major cause of cancer-related mortality worldwide.GC is determined by multiple(epi)genetic and environmental factors;can occur at distinct anatomic positions of the stomach;and displays high het...Gastric cancer(GC)is a major cause of cancer-related mortality worldwide.GC is determined by multiple(epi)genetic and environmental factors;can occur at distinct anatomic positions of the stomach;and displays high heterogeneity,with different cellular origins and diverse histological and molecular features.This heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient therapeutics.In the past decade,great progress has been made in the study of GC,particularly in molecular subtyping,investigation of the immune microenvironment,and defining the evolutionary path and dynamics.Preclinical mouse models,particularly immunocompetent models that mimic the cellular and molecular features of human GC,in combination with organoid culture and clinical studies,have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion,and the development of novel therapeutic strategies.Herein,we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models,emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.展开更多
Meningoencephalitis secondary to Listeria monocytogenes (L. monocytogenes) mainly affects newborns, the elderly and immunocompromised people;there are extremely rare cases in which said infection occurs in immunocompe...Meningoencephalitis secondary to Listeria monocytogenes (L. monocytogenes) mainly affects newborns, the elderly and immunocompromised people;there are extremely rare cases in which said infection occurs in immunocompetent individuals. We present the case of a young adult patient without immunocompromise, who developed meningoencephalitis due to L. monocytogenes;This case is exceptional, since it occurred in an individual outside the classic age group, in addition to not having risk factors, which is why it should be considered an atypical causal agent.展开更多
Introduction: Herpetic esophagitis (HE) is an esophageal infection caused by herpes simplex virus (HSV). It commonly occurs in immunosuppressive patients but rarely affects immunocompetent people. It presents with ody...Introduction: Herpetic esophagitis (HE) is an esophageal infection caused by herpes simplex virus (HSV). It commonly occurs in immunosuppressive patients but rarely affects immunocompetent people. It presents with odynophagia, dysphagia and/or retrosternal pain. An upper gastrointestinal endoscopy with biopsy is essential to establish the diagnosis. Case Description: This is a rare case of a patient who presented to our endoscopic department complaining of epigastric pain, gradual worsening of odynophagia and mild dysphagia within one month with a medical history of hypercholesterinemia and hypertension. He had no history of immunosuppression, or any risk factor for HE such as malnutrition, excessive alcohol consumption or use of corticosteroids, not even gastroesophageal reflux disease. An upper gastrointestinal endoscopy was performed, revealing multiple erosions and ulcers at distal esophagus. Biopsies from the margins of the ulcers and PCR led to the diagnosis of herpetic esophagitis. Due to the severe symptoms, despite the immunocompetent status treatment of acyclovir was administrated leading to a gradual improvement of the symptoms. Conclusion: This case highlights that HE could exist in an immunocompetent patient despite the rarity of occurrence and therefore physicians should have a high level of suspicion to make the diagnosis.展开更多
Critically ill patients are a vulnerable group at high risk of developing secondary infections.High disease severity,prolonged intensive care unit(ICU)stay,sepsis,and multiple drugs with immunosuppressive activity mak...Critically ill patients are a vulnerable group at high risk of developing secondary infections.High disease severity,prolonged intensive care unit(ICU)stay,sepsis,and multiple drugs with immunosuppressive activity make these patients prone to immuneparesis and increase the risk of various opportunistic infections,including cytomegalovirus(CMV).CMV seroconversion has been reported in up to 33%of ICU patients,but its impact on patient outcomes remains a matter of debate.Even though there are guidelines regarding the management of CMV infection in immunosuppressive patients with human immunodeficiency virus/acquired immuno deficiency syndrome,the need for treatment and therapeutic approaches in immunocompetent critically ill patients is still ambiguous.Even the diagnosis of CMV infection may be challenging in such patients due to non-specific symptoms and multiorgan involvement.Hence,a better understanding of the symptomatology,diagnostics,and treatment options may aid intensive care physicians in ensuring accurate diagnoses and instituting therapeutic interventions.展开更多
Bartonella species are bacterial pathogens responsible for Cat Scratch Disease (CSD) with various clinical manifestations, ranging from self-limiting febrile illnesses to severe systemic infections. Diagnosis is often...Bartonella species are bacterial pathogens responsible for Cat Scratch Disease (CSD) with various clinical manifestations, ranging from self-limiting febrile illnesses to severe systemic infections. Diagnosis is often challenging due to its insidious nature and variable presentation based on the body’s immune status. Such a scenario emerged when a 25-year-old male presented to our hospital with nonspecific symptoms of Fever of unknown origin that were not responding to antibiotics until a timely diagnosis of Bartonella infection. This case report highlights the importance of considering Bartonella as a potential etiology in patients with prolonged Fever of unknown origin, especially in endemic regions.展开更多
Bacterial meningitis, due to Listeria monocytogenes, is an invasive central nervous infection, commonly reported in high-risk subjects such as pregnant women, infants, the elderly and immunocompromised patients. Howev...Bacterial meningitis, due to Listeria monocytogenes, is an invasive central nervous infection, commonly reported in high-risk subjects such as pregnant women, infants, the elderly and immunocompromised patients. However, in health immunocompetent individuals, bacterial meningitis by this pathogen is extremely rare. Here, we report a case of meningitis due to Listeria monocytogenes in a healthy immunocompetent 10-year-old male child in Cameroon. The child was successfully treated with intravenous ampicillin and recovered without any neurological sequelae. Monitoring, set-up of prompt diagnosis as well as the administration of an adequate antibiotic treatment is essential to both prevent emergence of new case and achieve the best treatment outcome.展开更多
As a common cause of viral encephalitis,varicella-zoster virus(VZV)may invade the central nervous system of immunosuppressed patients during reactivation.Herein,we report a rare case of an immunocompetent patient with...As a common cause of viral encephalitis,varicella-zoster virus(VZV)may invade the central nervous system of immunosuppressed patients during reactivation.Herein,we report a rare case of an immunocompetent patient with VZV encephalitis who developed severe hyponatremia and was considered to have a suspected primary infection.The patient was diagnosed with the support of second-generation sequencing and had persistent hyponatremia after being cured.Although rare,this case suggests that VZV encephalitis may occur in unexpected patients and present with unusual clinical manifestations,requiring advanced detection methods and clinical expertise for resolution.展开更多
[Objective] The purification and immunocompetence of GPS protein in porcine reproductive and respiratory syndrome (PRRS) were analyzed in this study, which provided basis for establishing the corresponding serological...[Objective] The purification and immunocompetence of GPS protein in porcine reproductive and respiratory syndrome (PRRS) were analyzed in this study, which provided basis for establishing the corresponding serological method. [Method] The recombinant expression plasmid pGEX-6P-5 was transformed into BL21 and expressed after being induced with IPTG. The solubility analysis of expression products was carried out, and then the recombinant protein was purified for SDS-PAGE identification and Western-blot analysis. Finally, the recombinant antigen was used in the immune experiment of guinea pigs. [Result] The target protein content accounted for 30% of the total cells protein content according to the chromatography scanning, and the purity of target protein after purification reached 80%. The purified protein was analyzed by Western-blot and immune experiment of guinea pigs, and the results showed that the expressed protein had good reactionogenicity and immunogenicity. [Conclusion] This study provides materials for further studies on the function between PRRSV ORF5 gene and its editing protein, which also lays a foundation for porcine reproductive and respiratory syndrome virus genetic engineering products.展开更多
Habitat alterations in agroecosystems may damage amphibian immune capacity. As agroecosystem extension is increasing worldwide, broader-context knowledge on the effects of agroecosystem stressful conditions on amphibi...Habitat alterations in agroecosystems may damage amphibian immune capacity. As agroecosystem extension is increasing worldwide, broader-context knowledge on the effects of agroecosystem stressful conditions on amphibian immune capacity is crucial for understanding and management of amphibian global declines. However, most studies on ecoimmunology assume synchronal amonggroup immune-response peaks, and focus on immune response after standardized time lapses, neglecting its progress!on. Herein, I compared inflamatory response short-term progression of agro ecosystem and n atural-habitat female and male n atterjack toads Epi da lea calamita, by measuri ng swelling response, once per hour, 6 h following an artificial immune challenge with innocuous antigen phytohemagglutinin. I also compared maximum magnitude of swelling response, irrespective of the moment when it was reached. Habitat differences arose only 3 h after challenge, when naturalhabitat toads showed greater swelling response. Maximum magnitude of swelling response was similar in toads from both habitats. However, agroecosystem toads showed a delayed swelling response as compared with natural-habitat conspecifics, probably as a consequenee of agroecosystem stressful conditions. Such a delay suggests a weaker immune capacity, and consequently impaired anti-pathogen performance. Regarding sex, swelling response magnitude did not differ between males and females. Female swelling response peaked earlier, but that of males was more sustai ned in time, which con tradicts general across-taxa fin dings that males show impaired immune response. Interestingly, results suggest that measuring swelling response only after some standardized period following stimulation may be a simplistic approach and produce unrealistic results. Consequently, studies on ecoimmunology should implement swelling response progression in order to produce unbiased science.展开更多
Aim To study the distribution pattern, antineoplastic activity and immunocompetence of a novel organoselenium compound Eb and investigate its in vivo antineoplastic potential. Methods Eb was administered to Kunming ...Aim To study the distribution pattern, antineoplastic activity and immunocompetence of a novel organoselenium compound Eb and investigate its in vivo antineoplastic potential. Methods Eb was administered to Kunming mice (dosage, 0.1 g·kg^(-1)·d^(-1)) intragastrically for 7 successive days. The contents of selenium in heart, liver, spleen, kidneys, lungs, stomach, brain, muscle, and bone were determined by fluorometric method on the eighth day. MTT assay was used to study tumor growth inhibition of Eb in vitro, and lymphocyte transformation, hemolysin formation and phagocytosis assay were used to study its immunocompetence. Results After 7 days′ administration of Eb, the tissue contents of sele-(nium) in liver, spleen, lungs, kidneys, and bone of mice increased, especially those in liver and spleen increased significan-tly, compared with controls; but no significant changes of such contents were found in muscle, heart, brain, and stomach. Eb demonstrated inhibitory effects on human Bel-7402, BGC-823, and Calu-3 cancer cell lines in vitro. Eb also showed ability to enhance lymphocyte transformation and serum hemolysin formation in vitro and increase the phagocytosis of macrophages. Conclusion The validated antitumor and immunostimulatory activities of Eb suggest a hypothesis that Eb may behave as a biological response modifier when used as an antitumor agent. Eb is worthy of further study in developing a new antineoplastic and immunity enhancing agent in the light of its antitumor activity, immunocompetence and specific distribution in liver, lungs, kidneys, bone, and spleen.展开更多
Varicella-zoster virus(VZV)is a type of herpes virus known to cause varicella,mainly in young children,and herpes zoster in adults.Although generally non-lethal,VZV infection can be associated with serious complicatio...Varicella-zoster virus(VZV)is a type of herpes virus known to cause varicella,mainly in young children,and herpes zoster in adults.Although generally non-lethal,VZV infection can be associated with serious complications,particularly in adults.Acute pancreatitis caused by VZV infection is a rare event,with reports primarily concerning immunocompromised individuals.Here we report a 44-year-old immunocompetent female who developed acute pancreatitis associated with VZV infection.The patient presented with vomiting and persistent pain in the upper quadrant less than one week after diagnosis and treatment for a herpes zoster-related rash with stabbing pain on the abdomen and dorsal right trunk side.A diagnosis of acute pancreatitis was confirmed based on abdominal pain,elevated levels of urine and serum amylase,and findings of peri-pancreatic exudation and effusions by computed tomography and magnetic resonance cholangiopancreatography.This case highlights that,though rare,acute pancreatitis should be considered in VZV patients who complain of abdominal pain,especially in the epigastric area.Early detection and proper treatment are needed to prevent the condition from deteriorating further and to minimize mortality.展开更多
BACKGROUND: The use of corticosteroids in septic shock has been studied for many decades but yielded conflicting results. We conducted a systematic review to evaluate the efficacy and the safety of corticosteroids in ...BACKGROUND: The use of corticosteroids in septic shock has been studied for many decades but yielded conflicting results. We conducted a systematic review to evaluate the efficacy and the safety of corticosteroids in immunocompetent patients with septic shock.METHODS: Medline via Pub Med, Cochrane Central Register of Controlled Trials(CENTRAL) in the Cochrane Library, and EMBASE were searched from inception to March 2020. Two reviewers independently identified randomized controlled trials(RCTs) comparing corticosteroids with a control group for immunocompetent patients with septic shock. Data were abstracted and reported following the Cochrane Handbook for Systematic Review of Intervention and Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) statement. The efficacy outcome included mortality and shock reversal. The safety outcomes were infection, gastrointestinal bleeding, and hyperglycemia.RESULTS: Nine RCTs with a total of 1,298 patients were included. Compared with the control group, corticosteroid group did not lower the short-term(28 or 30 days) mortality(risk ratio [RR] 0.95, 95% confidence interval(CI) 0.85 to 1.06, inconsistency [I2]=0%, trial sequential analysis [TSA]-adjusted CI 0.83 to 1.09, moderate-certainty evidence). Corticosteroids significantly shortened the time to shock reversal compared with the control group(mean difference [MD] –21.56 hours;95% CI –32.95 to –10.16, I2=0%;TSA-adjusted CI –33.33 to –9.78, moderate-certainty evidence). The corticosteroid treatment was associated with an increased risk of hyperglycemia but not the infection or gastrointestinal bleeding.CONCLUSIONS: The corticosteroid treatment is not associated with lower short-or longterm mortality compared with placebo in immunocompetent patients with septic shock. However, corticosteroids significantly shorten the time to shock reversal without increasing the risk of infection. The patient's immune status should also be considered during clinical treatment and clinical trials in future.展开更多
Utilizing collagen of sheep bone as material to get immunocompetent peptide, enzymatic hydrolysis conditions were optimized using quadratic regression general rotation design. The effect of temperature （T）, time （t...Utilizing collagen of sheep bone as material to get immunocompetent peptide, enzymatic hydrolysis conditions were optimized using quadratic regression general rotation design. The effect of temperature （T）, time （t）, enzyme/substrate （E/S） ratio, and substrate concentration （S） on the amount of tricarboxylix acid cycle （TCA） soluble peptides were investigated. The content of soluble peptide in the acquisition was measured by Folin-hydrozybebzebe method, and the correlation between soluble peptide content and immunocompetence was analyzed by SAS software. The best enzymatic hydrolysis condition was gotten from Design Expert 7.1.2 software. The optimal condition under which immunocompetent peptides could be prepared was 1 576 U g^-1 （E/S）, 64.05℃ （T）, 0.271 kg L^-1 （S）, and 7.22 h （t）. The correlation coefficient between TCA soluble peptides and the immuneocompetence was 0.045 〈r0.05 = 0.355, which indicated that they had no significant correlation. The result showed that the soluble peptide contained immunocompetent peptides which content was independent of immunocompetence in the hydrolasates.展开更多
Municipal wastewaters are major sources of pollution for the aquatic biota. The purpose of this study was to determine the levels of some pharmaceutical products and the immunotoxic potential of a municipal wastewater...Municipal wastewaters are major sources of pollution for the aquatic biota. The purpose of this study was to determine the levels of some pharmaceutical products and the immunotoxic potential of a municipal wastewater aeration lagoon for the treatment of the domestic wastewaters of a small town with wastewater inputs from a 400-bed hospital complex. Endemic mussels were collected, caged and placed in the final aeration lagoon and at sites 1 km upstream and 1 km downstream of the effluent outfall in the receiving river for a period of 14 days. The results showed that the final aeration lagoon contained high levels of total coliforms, conductivity and low dissolved oxygen （2.9 mg/L） as well as detectable amounts of trimethoprim, carbamazepine, gemfibrozil, and norfloxacin at concentrations exceeding 50 ng/L. The lagoon effluent was indeed toxic to the mussel specimens, as evidenced by the appearance of mortality after 14 days （10% mortality）, decreased mussel weight-to-shell-length ratio and loss of hemocyte viability. The number of adhering hemocytes, phagocytic activity, total nitrite levels and arachidonic cyclooxygenase activity were significantly higher in mussels placed in the final aeration lagoon. A multivariate analysis also revealed that water pH, conductivity, total coliforms and dissolved oxygen were the endpoints most closely linked with phagocytic activity, the amount of adhering hemocytes and loss of hemocyte viability. In conclusion, exposure of mussels to treated aerated lagoon wastewater is deleterious to freshwater mussels where the immune system is compromised.展开更多
基金funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skodowska-Curie grant agreement No.813263(PMSMat Train,granted to UF,PP,MV,and DP)provided by the Fund for Scientific Research Flanders(FWO-Vlaanderen)of the Flemish Government(FWO sabbatical bench fee K800224N granted to PP)and ERA-NET Re Park(granted to PP)。
文摘Brain organoids encompass a large collection of in vitro stem cell–derived 3D culture systems that aim to recapitulate multiple aspects of in vivo brain development and function.First,this review provides a brief introduction to the current state-of-the-art for neuroectoderm brain organoid development,emphasizing their biggest advantages in comparison with classical two-dimensional cell cultures and animal models.However,despite their usefulness for developmental studies,a major limitation for most brain organoid models is the absence of contributing cell types from endodermal and mesodermal origin.As such,current research is highly investing towards the incorporation of a functional vasculature and the microglial immune component.In this review,we will specifically focus on the development of immune-competent brain organoids.By summarizing the different approaches applied to incorporate microglia,it is highlighted that immune-competent brain organoids are not only important for studying neuronal network formation,but also offer a clear future as a new tool to study inflammatory responses in vitro in 3D in a brainlike environment.Therefore,our main focus here is to provide a comprehensive overview of assays to measure microglial phenotype and function within brain organoids,with an outlook on how these findings could better understand neuronal network development or restoration,as well as the influence of physical stress on microglia-containing brain organoids.Finally,we would like to stress that even though the development of immune-competent brain organoids has largely evolved over the past decade,their full potential as a pre-clinical tool to study novel therapeutic approaches to halt or reduce inflammation-mediated neurodegeneration still needs to be explored and validated.
基金supported by Conselho Nacional de Desenvolvimento Cientifco e Tecnologico(CNPq),Fundacaode Amparoa Pesquisa do Rio de Janeiro(FAPERJ),Fundacaode Amparoa Pesquisa do Estado de Sao Paulo(FAPESPGrant nº2014/16/320-7)Coordenacao de Aperfeicoamentode Pessoal de Nível Superior(CAPES)-Finance Code 001+1 种基金by grants to LGHM and APCN from the Visiting Research Program of the FAPESP(nº2017-17607-6)supported by the PASPA-DGAPA program of the Universidad Nacional Autonoma de Mexico(nº814-2018).
文摘Developmental instability(DI)is a phenomenon whereby organisms are unable to buffer developmental disturbances,resulting in asymmetricvariation of paired traits.Previous research has demonstrated a negative relationship between DI,measured as forearm asymmetry,and survivalin the bat Carollia perspicillata.This study aims to test the hypothesis that individuals with higher DI exhibit a lower immune response.We measured a delayed-type hypersensitivity to the antigen phytohemagglutinin(PHA)on 74 males and 65 females of C.perspicillata before and after thebreeding season(BS).Linear models were used to predict the immunological response based on body mass(BM),forearm asymmetry,sex,BS,and testicle length.The best-ftting model accounted for 29% of the variation in immune response and included asymmetry,BM,sex,and BS aspredictors.The immune response was negatively associated with asymmetry and testicle length in males but positively related to asymmetryin females.Both sexes showed a reduced immune response in the late BS.Additionally,the association between immune response and BMchanged direction seasonally,with heavier individuals showing weaker responses early in the BS and stronger responses later.Individual variation in male immunity was predicted by individual attributes,whereas variation in immune response in females was mostly seasonal.Our resultssupport the link between DI,survival,and immune response in short-tailed bats,and suggest that the immunological component measured bythe PHA response may be under fner selection in males due to its stronger correlation with individual traits.
文摘Background Enterotoxigenic Escherichia coli(E.coli)is a threat to humans and animals that causes intestinal dis-orders.Antimicrobial resistance has urged alternatives,including Lactobacillus postbiotics,to mitigate the effects of enterotoxigenic E.coli.Methods Forty-eight newly weaned pigs were allotted to NC:no challenge/no supplement;PC:F18^(+)E.coli chal-lenge/no supplement;ATB:F18^(+)E.coli challenge/bacitracin;and LPB:F18^(+)E.coli challenge/postbiotics and fed diets for 28 d.On d 7,pigs were orally inoculated withF18^(+)E.coli.At d 28,the mucosa-associated microbiota,immune and oxidative stress status,intestinal morphology,the gene expression of pattern recognition receptors(PRR),and intestinal barrier function were measured.Data were analyzed using the MIXED procedure in SAS 9.4.Results PC increased(P<0.05)Helicobacter mastomyrinus whereas reduced(P<0.05)Prevotella copri and P.ster-corea compared to NC.The LPB increased(P<0.05)P.stercorea and Dialister succinatiphilus compared with PC.The ATB increased(P<0.05)Propionibacterium acnes,Corynebacterium glutamicum,and Sphingomonas pseudosanguinis compared to PC.The PC tended to reduce(P=0.054)PGLYRP4 and increased(P<0.05)TLR4,CD14,MDA,and crypt cell proliferation compared with NC.The ATB reduced(P<0.05)NOD1 compared with PC.The LPB increased(P<0.05)PGLYRP4,and interferon-γand reduced(P<0.05)NOD1 compared with PC.The ATB and LPB reduced(P<0.05)TNF-αand MDA compared with PC.Conclusions TheF18^(+)E.coli challenge compromised intestinal health.Bacitracin increased beneficial bacteria show-ing a trend towards increasing the intestinal barrier function,possibly by reducing the expression of PRR genes.Lac-tobacillus postbiotics enhanced the immunocompetence of nursery pigs by increasing the expression of interferon-γand PGLYRP4,and by reducing TLR4,NOD1,and CD14.
文摘BACKGROUND Histoplasmosis is a rare infectious condition with mainly pulmonary involvement which is generally self-limiting in immunocompetent individuals.Its manifestation varies and lacks specificity.This study reports a case of primary disseminated liver histoplasmosis in a normal host presenting as liver failure cured by liver transplantation and voriconazole.CASE SUMMARY A 43-year-old Chinese man with intermittent fever,malaise,jaundice and extreme hepatomegaly for more than 40 days was admitted to the Second Xiang-ya Hospital.The patient was immunocompetent and lacked a definitive history of exposure.His condition deteriorated to liver failure,and he promptly underwent liver transplantation to ensure survival.One year later,the patient presented with severe gastrointestinal symptoms,including fever,abdominal pain,and diarrhea.Subsequently,tissue samples acquired via gastrointestinal endoscopy were subjected to pathological examination and next-generation sequencing analysis.Through a comprehensive amalgamation of clinical presentation,biopsy pathology,and next-generation sequencing analysis,the patient was ultimately diagnosed with disseminated hepatic histoplasmosis.The patient achieved complete recovery after 6 months of voriconazole treatment.CONCLUSION In patients with chronic-hepatitis-B having atypical symptoms,histoplasmosis can be a differential diagnosis.Voriconazole is effective in treating histoplasmosis.
文摘We examined the case report written by Ke et al,describing a rare clinical case.In this editorial,we would like to emphasize the differential diagnosis of rectal masses through a rare case.We describe a case of ameboma,which manifested itself as a mass in the rectum in terms of imaging and rectoscopic features,in an immunocompetent patient who had complaints of constipation and rectal bleeding for weeks.The initial diagnosis suggested malignancy due to imaging and rectoscopic features,but the pathology report reported it as amoebiasis.After ten days of metronidazole and oral amebicide(diloxanide furoate)treatment,the patient’s symptoms and radiological findings were successfully regressed.
文摘Human herpesvirus 6(HHV-6)is a common childhood infection but rarely causes severe complications.In immunocompetent children,conditions such as febrile convulsions and roseola infantum are typical,with occasional severe manifestations like meningoencephalitis and myocarditis.
基金supported by the National Key R&D Program of China(Grant No.2020YFA0803200 and 2023YFC2505903)National Natural Science Foundation of China(Grant Nos.82003014,31930026,81972876,82150112,92168116,81725014,81822035,and 82222052)+1 种基金China Postdoctoral Science Foundation(Grant No.2020M671231)Fundamental Research Funds for the Central Universities(Grant No.22120240327)。
文摘Gastric cancer(GC)is a major cause of cancer-related mortality worldwide.GC is determined by multiple(epi)genetic and environmental factors;can occur at distinct anatomic positions of the stomach;and displays high heterogeneity,with different cellular origins and diverse histological and molecular features.This heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient therapeutics.In the past decade,great progress has been made in the study of GC,particularly in molecular subtyping,investigation of the immune microenvironment,and defining the evolutionary path and dynamics.Preclinical mouse models,particularly immunocompetent models that mimic the cellular and molecular features of human GC,in combination with organoid culture and clinical studies,have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion,and the development of novel therapeutic strategies.Herein,we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models,emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.
文摘Meningoencephalitis secondary to Listeria monocytogenes (L. monocytogenes) mainly affects newborns, the elderly and immunocompromised people;there are extremely rare cases in which said infection occurs in immunocompetent individuals. We present the case of a young adult patient without immunocompromise, who developed meningoencephalitis due to L. monocytogenes;This case is exceptional, since it occurred in an individual outside the classic age group, in addition to not having risk factors, which is why it should be considered an atypical causal agent.
文摘Introduction: Herpetic esophagitis (HE) is an esophageal infection caused by herpes simplex virus (HSV). It commonly occurs in immunosuppressive patients but rarely affects immunocompetent people. It presents with odynophagia, dysphagia and/or retrosternal pain. An upper gastrointestinal endoscopy with biopsy is essential to establish the diagnosis. Case Description: This is a rare case of a patient who presented to our endoscopic department complaining of epigastric pain, gradual worsening of odynophagia and mild dysphagia within one month with a medical history of hypercholesterinemia and hypertension. He had no history of immunosuppression, or any risk factor for HE such as malnutrition, excessive alcohol consumption or use of corticosteroids, not even gastroesophageal reflux disease. An upper gastrointestinal endoscopy was performed, revealing multiple erosions and ulcers at distal esophagus. Biopsies from the margins of the ulcers and PCR led to the diagnosis of herpetic esophagitis. Due to the severe symptoms, despite the immunocompetent status treatment of acyclovir was administrated leading to a gradual improvement of the symptoms. Conclusion: This case highlights that HE could exist in an immunocompetent patient despite the rarity of occurrence and therefore physicians should have a high level of suspicion to make the diagnosis.
文摘Critically ill patients are a vulnerable group at high risk of developing secondary infections.High disease severity,prolonged intensive care unit(ICU)stay,sepsis,and multiple drugs with immunosuppressive activity make these patients prone to immuneparesis and increase the risk of various opportunistic infections,including cytomegalovirus(CMV).CMV seroconversion has been reported in up to 33%of ICU patients,but its impact on patient outcomes remains a matter of debate.Even though there are guidelines regarding the management of CMV infection in immunosuppressive patients with human immunodeficiency virus/acquired immuno deficiency syndrome,the need for treatment and therapeutic approaches in immunocompetent critically ill patients is still ambiguous.Even the diagnosis of CMV infection may be challenging in such patients due to non-specific symptoms and multiorgan involvement.Hence,a better understanding of the symptomatology,diagnostics,and treatment options may aid intensive care physicians in ensuring accurate diagnoses and instituting therapeutic interventions.
文摘Bartonella species are bacterial pathogens responsible for Cat Scratch Disease (CSD) with various clinical manifestations, ranging from self-limiting febrile illnesses to severe systemic infections. Diagnosis is often challenging due to its insidious nature and variable presentation based on the body’s immune status. Such a scenario emerged when a 25-year-old male presented to our hospital with nonspecific symptoms of Fever of unknown origin that were not responding to antibiotics until a timely diagnosis of Bartonella infection. This case report highlights the importance of considering Bartonella as a potential etiology in patients with prolonged Fever of unknown origin, especially in endemic regions.
文摘Bacterial meningitis, due to Listeria monocytogenes, is an invasive central nervous infection, commonly reported in high-risk subjects such as pregnant women, infants, the elderly and immunocompromised patients. However, in health immunocompetent individuals, bacterial meningitis by this pathogen is extremely rare. Here, we report a case of meningitis due to Listeria monocytogenes in a healthy immunocompetent 10-year-old male child in Cameroon. The child was successfully treated with intravenous ampicillin and recovered without any neurological sequelae. Monitoring, set-up of prompt diagnosis as well as the administration of an adequate antibiotic treatment is essential to both prevent emergence of new case and achieve the best treatment outcome.
文摘As a common cause of viral encephalitis,varicella-zoster virus(VZV)may invade the central nervous system of immunosuppressed patients during reactivation.Herein,we report a rare case of an immunocompetent patient with VZV encephalitis who developed severe hyponatremia and was considered to have a suspected primary infection.The patient was diagnosed with the support of second-generation sequencing and had persistent hyponatremia after being cured.Although rare,this case suggests that VZV encephalitis may occur in unexpected patients and present with unusual clinical manifestations,requiring advanced detection methods and clinical expertise for resolution.
基金Supported by National High-tech Research and Development Plan (863 Project) in the Eleventh Five-Year Plan Period (2006AA10A207)~~
文摘[Objective] The purification and immunocompetence of GPS protein in porcine reproductive and respiratory syndrome (PRRS) were analyzed in this study, which provided basis for establishing the corresponding serological method. [Method] The recombinant expression plasmid pGEX-6P-5 was transformed into BL21 and expressed after being induced with IPTG. The solubility analysis of expression products was carried out, and then the recombinant protein was purified for SDS-PAGE identification and Western-blot analysis. Finally, the recombinant antigen was used in the immune experiment of guinea pigs. [Result] The target protein content accounted for 30% of the total cells protein content according to the chromatography scanning, and the purity of target protein after purification reached 80%. The purified protein was analyzed by Western-blot and immune experiment of guinea pigs, and the results showed that the expressed protein had good reactionogenicity and immunogenicity. [Conclusion] This study provides materials for further studies on the function between PRRSV ORF5 gene and its editing protein, which also lays a foundation for porcine reproductive and respiratory syndrome virus genetic engineering products.
文摘Habitat alterations in agroecosystems may damage amphibian immune capacity. As agroecosystem extension is increasing worldwide, broader-context knowledge on the effects of agroecosystem stressful conditions on amphibian immune capacity is crucial for understanding and management of amphibian global declines. However, most studies on ecoimmunology assume synchronal amonggroup immune-response peaks, and focus on immune response after standardized time lapses, neglecting its progress!on. Herein, I compared inflamatory response short-term progression of agro ecosystem and n atural-habitat female and male n atterjack toads Epi da lea calamita, by measuri ng swelling response, once per hour, 6 h following an artificial immune challenge with innocuous antigen phytohemagglutinin. I also compared maximum magnitude of swelling response, irrespective of the moment when it was reached. Habitat differences arose only 3 h after challenge, when naturalhabitat toads showed greater swelling response. Maximum magnitude of swelling response was similar in toads from both habitats. However, agroecosystem toads showed a delayed swelling response as compared with natural-habitat conspecifics, probably as a consequenee of agroecosystem stressful conditions. Such a delay suggests a weaker immune capacity, and consequently impaired anti-pathogen performance. Regarding sex, swelling response magnitude did not differ between males and females. Female swelling response peaked earlier, but that of males was more sustai ned in time, which con tradicts general across-taxa fin dings that males show impaired immune response. Interestingly, results suggest that measuring swelling response only after some standardized period following stimulation may be a simplistic approach and produce unrealistic results. Consequently, studies on ecoimmunology should implement swelling response progression in order to produce unbiased science.
文摘Aim To study the distribution pattern, antineoplastic activity and immunocompetence of a novel organoselenium compound Eb and investigate its in vivo antineoplastic potential. Methods Eb was administered to Kunming mice (dosage, 0.1 g·kg^(-1)·d^(-1)) intragastrically for 7 successive days. The contents of selenium in heart, liver, spleen, kidneys, lungs, stomach, brain, muscle, and bone were determined by fluorometric method on the eighth day. MTT assay was used to study tumor growth inhibition of Eb in vitro, and lymphocyte transformation, hemolysin formation and phagocytosis assay were used to study its immunocompetence. Results After 7 days′ administration of Eb, the tissue contents of sele-(nium) in liver, spleen, lungs, kidneys, and bone of mice increased, especially those in liver and spleen increased significan-tly, compared with controls; but no significant changes of such contents were found in muscle, heart, brain, and stomach. Eb demonstrated inhibitory effects on human Bel-7402, BGC-823, and Calu-3 cancer cell lines in vitro. Eb also showed ability to enhance lymphocyte transformation and serum hemolysin formation in vitro and increase the phagocytosis of macrophages. Conclusion The validated antitumor and immunostimulatory activities of Eb suggest a hypothesis that Eb may behave as a biological response modifier when used as an antitumor agent. Eb is worthy of further study in developing a new antineoplastic and immunity enhancing agent in the light of its antitumor activity, immunocompetence and specific distribution in liver, lungs, kidneys, bone, and spleen.
基金Supported by Zhejiang Provincial Natural Science Foundation of China No.LY14H160027,No.LQ12H16009the Science and Technology Bureau of Zhejiang Province,No.2013C33137,No.2013KKYA093
文摘Varicella-zoster virus(VZV)is a type of herpes virus known to cause varicella,mainly in young children,and herpes zoster in adults.Although generally non-lethal,VZV infection can be associated with serious complications,particularly in adults.Acute pancreatitis caused by VZV infection is a rare event,with reports primarily concerning immunocompromised individuals.Here we report a 44-year-old immunocompetent female who developed acute pancreatitis associated with VZV infection.The patient presented with vomiting and persistent pain in the upper quadrant less than one week after diagnosis and treatment for a herpes zoster-related rash with stabbing pain on the abdomen and dorsal right trunk side.A diagnosis of acute pancreatitis was confirmed based on abdominal pain,elevated levels of urine and serum amylase,and findings of peri-pancreatic exudation and effusions by computed tomography and magnetic resonance cholangiopancreatography.This case highlights that,though rare,acute pancreatitis should be considered in VZV patients who complain of abdominal pain,especially in the epigastric area.Early detection and proper treatment are needed to prevent the condition from deteriorating further and to minimize mortality.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS)(2020-I2M-C&T-B-014)CAMS Teaching Reform Research Fund(2018zlgc0101)CAMS Online Open Course Construction Fund(J2009022861)。
文摘BACKGROUND: The use of corticosteroids in septic shock has been studied for many decades but yielded conflicting results. We conducted a systematic review to evaluate the efficacy and the safety of corticosteroids in immunocompetent patients with septic shock.METHODS: Medline via Pub Med, Cochrane Central Register of Controlled Trials(CENTRAL) in the Cochrane Library, and EMBASE were searched from inception to March 2020. Two reviewers independently identified randomized controlled trials(RCTs) comparing corticosteroids with a control group for immunocompetent patients with septic shock. Data were abstracted and reported following the Cochrane Handbook for Systematic Review of Intervention and Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) statement. The efficacy outcome included mortality and shock reversal. The safety outcomes were infection, gastrointestinal bleeding, and hyperglycemia.RESULTS: Nine RCTs with a total of 1,298 patients were included. Compared with the control group, corticosteroid group did not lower the short-term(28 or 30 days) mortality(risk ratio [RR] 0.95, 95% confidence interval(CI) 0.85 to 1.06, inconsistency [I2]=0%, trial sequential analysis [TSA]-adjusted CI 0.83 to 1.09, moderate-certainty evidence). Corticosteroids significantly shortened the time to shock reversal compared with the control group(mean difference [MD] –21.56 hours;95% CI –32.95 to –10.16, I2=0%;TSA-adjusted CI –33.33 to –9.78, moderate-certainty evidence). The corticosteroid treatment was associated with an increased risk of hyperglycemia but not the infection or gastrointestinal bleeding.CONCLUSIONS: The corticosteroid treatment is not associated with lower short-or longterm mortality compared with placebo in immunocompetent patients with septic shock. However, corticosteroids significantly shorten the time to shock reversal without increasing the risk of infection. The patient's immune status should also be considered during clinical treatment and clinical trials in future.
基金founded by the Scientific and Technological Project of Tianjin,China (05ZHGCN00100)
文摘Utilizing collagen of sheep bone as material to get immunocompetent peptide, enzymatic hydrolysis conditions were optimized using quadratic regression general rotation design. The effect of temperature （T）, time （t）, enzyme/substrate （E/S） ratio, and substrate concentration （S） on the amount of tricarboxylix acid cycle （TCA） soluble peptides were investigated. The content of soluble peptide in the acquisition was measured by Folin-hydrozybebzebe method, and the correlation between soluble peptide content and immunocompetence was analyzed by SAS software. The best enzymatic hydrolysis condition was gotten from Design Expert 7.1.2 software. The optimal condition under which immunocompetent peptides could be prepared was 1 576 U g^-1 （E/S）, 64.05℃ （T）, 0.271 kg L^-1 （S）, and 7.22 h （t）. The correlation coefficient between TCA soluble peptides and the immuneocompetence was 0.045 〈r0.05 = 0.355, which indicated that they had no significant correlation. The result showed that the soluble peptide contained immunocompetent peptides which content was independent of immunocompetence in the hydrolasates.
基金funded by the research program on municipal effluents of Environment Canada
文摘Municipal wastewaters are major sources of pollution for the aquatic biota. The purpose of this study was to determine the levels of some pharmaceutical products and the immunotoxic potential of a municipal wastewater aeration lagoon for the treatment of the domestic wastewaters of a small town with wastewater inputs from a 400-bed hospital complex. Endemic mussels were collected, caged and placed in the final aeration lagoon and at sites 1 km upstream and 1 km downstream of the effluent outfall in the receiving river for a period of 14 days. The results showed that the final aeration lagoon contained high levels of total coliforms, conductivity and low dissolved oxygen （2.9 mg/L） as well as detectable amounts of trimethoprim, carbamazepine, gemfibrozil, and norfloxacin at concentrations exceeding 50 ng/L. The lagoon effluent was indeed toxic to the mussel specimens, as evidenced by the appearance of mortality after 14 days （10% mortality）, decreased mussel weight-to-shell-length ratio and loss of hemocyte viability. The number of adhering hemocytes, phagocytic activity, total nitrite levels and arachidonic cyclooxygenase activity were significantly higher in mussels placed in the final aeration lagoon. A multivariate analysis also revealed that water pH, conductivity, total coliforms and dissolved oxygen were the endpoints most closely linked with phagocytic activity, the amount of adhering hemocytes and loss of hemocyte viability. In conclusion, exposure of mussels to treated aerated lagoon wastewater is deleterious to freshwater mussels where the immune system is compromised.
