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
[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
Nocardiosis is a localized or disseminated infection caused by soil-borne aerobic actinomycetes. Pulmonary nocardiosis is a rare infection mostly occurring in immunocompromised patients.We reported a case of 36 year o...Nocardiosis is a localized or disseminated infection caused by soil-borne aerobic actinomycetes. Pulmonary nocardiosis is a rare infection mostly occurring in immunocompromised patients.We reported a case of 36 year old immunocompetent non-smoker female patient with no premorbid illness who presented with fever,cough with scanty sputum,hemoptysis,left sided chest pain and exertional dyspnea for two weeks.There was no past history of tuberculosis,diabetes mellitus or steroid therapy.Chest X-ray showed homogenous peripherally based opacity in the left upper zone.Bronchoscopy was done and brushing sent for culture,which showed colonies with features of Nocardia species after 48 hours.Further phenotypic characterization revealed it to be Nocardia otitidiscaviarum.Patient was treated with cotrimaxazole for six months after which complete recovery was evidenced symptomatically and radiologically.We report this case to emphasize the fact that among the Nocardia species,Nocardia otitidiscaviarum as causative agent of pulmonary disease is rarely reported even in immunocompromised individuals.展开更多
In order to investigate the immunoactivity of Lycium Barbarum glycopeptide (LBG), the routinely prepared murine splenic lymphocyte suspension was separately added into the samples with different concentrations (500, 1...In order to investigate the immunoactivity of Lycium Barbarum glycopeptide (LBG), the routinely prepared murine splenic lymphocyte suspension was separately added into the samples with different concentrations (500, 100, 10, 1 μg/ml) of LBG as LBG groups. Blank control group in the absence of Lycium Barbarum glycopeptide or ConA and positive control group in the presence of 0.5 ml ConA but in the absence of LBG were created. 0.5 ml LBG samples with different concentrations in combination with 0.5 ml ConA (10 μg/ml) into each well to observe the synergic effects of LBG and ConA as LBG+ConA groups. After incubation for 72 h at 37 ℃, the samples were analyzed by CFSE-labeled cells combined with flow cytometry, and MTT. Flow cytometry revealed that both LBG could enhance the murine splenic lymphocyte proliferative reaction. Combined use of LBG and ConA had synergic effects. MTT demonstrated that sample A could obviously promote the murine splenic lymphocyte proliferative reaction as compared with control group (P<0.01), while sample B could also enhance the lymphocyte proliferation at a high dose. In combination with ConA, sample A had synergic effects at high dose, while sample B showed obviously synergic effects (P<0.05). It was concluded that both samples (A and B) had strong immunocompetence.展开更多
Cytomegalovirus enteritis is most usually associated with patients positive for human immunodeficiency virus or immunosuppressed transplant patients. The gastrointestinal tract may be affected anywhere from the esopha...Cytomegalovirus enteritis is most usually associated with patients positive for human immunodeficiency virus or immunosuppressed transplant patients. The gastrointestinal tract may be affected anywhere from the esophagus to the colon, but the small bowel involvement is rare. We report a case of cytomegalovirus ileitis in an immunocompetent adult, which was confirmed by histopathologic findings through colonoscopic biopsy.展开更多
Herpes simplex esophagitis （HSE） is well documented in immunosuppressed patients. However, it is rare in the immunocompetent host. We present a case of HSE in a 21 year-old healthy lady who was admitted to our unit ...Herpes simplex esophagitis （HSE） is well documented in immunosuppressed patients. However, it is rare in the immunocompetent host. We present a case of HSE in a 21 year-old healthy lady who was admitted to our unit with dysphagia, odynophagia and chest pain. Clinical examination revealed mild epigastric tenderness and admission bloods including full blood picture, electrolytes and inflammatory markers were normal. She underwent an esophagogastroduodenoscopy （EGD） which revealed severe exudative, well-circumscribed ulcerations in her distal esophagus. Biopsies confirmed severe esophagitis with acute ulceration and subsequent polymerase chain reaction （PCR） confirmed herpes simplex virus （HSV） type 1. Subsequent assessment failed to identify an immune disorder. HSE should be suspected when faced with characteristic endoscopic findings, even if the patient is immunocompetent. When the diagnosis of HSE is confirmed, an immune deficiency should be sought.展开更多
AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human...AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.展开更多
Information regarding immunocompetence of the adaptive immune system （AIS） in zebrafish Danio rerio remains limited. Here, we stimulated an immune response in fish embryos, larvae and adults using lipopolysaccharide...Information regarding immunocompetence of the adaptive immune system （AIS） in zebrafish Danio rerio remains limited. Here, we stimulated an immune response in fish embryos, larvae and adults using lipopolysaccharide （LPS） and measured the upregulation of a number of AIS-related genes （Rag2, AID, TCRAC, IgLC-1, mIg, slg, IgZ and DAB） 3 and 18 h later. We found that all of the genes evaluated were strongly induced following LPS stimulation, with most of them responding at 8 d post fertilization. This confirms that a functional adaptive immune response is present in D. rerio larvae, and provides a window for further functional analyses.展开更多
BACKGROUND Pulmonary mucormycosis is a rare but life-threatening invasive fungal infection that mostly affects immunocompromised patients.This disease usually develops acutely and progresses rapidly,often leading to a...BACKGROUND Pulmonary mucormycosis is a rare but life-threatening invasive fungal infection that mostly affects immunocompromised patients.This disease usually develops acutely and progresses rapidly,often leading to a poor clinical prognosis.Chronic pulmonary mucormycosis is highly unusual in immunocompetent patients.CASE SUMMARY A 43-year-old man,who was a house improvement worker with a long history of occupational dust exposure,presented with an irritating cough that had lasted for two months.The patient was previously in good health,without dysglycemia or any known immunodeficiencies.Chest computed tomography revealed a mass in the left lower lobe,measuring approximately 6 cm in diameter,which was suspected to be primary lung carcinoma complicated with obstructive pneumonia.Thoracoscopic-assisted left lower lobectomy was performed,and metagenomic next-generation sequencing detection,along with special pathological staining of surgical specimens,suggested Rhizopus microsporus infection.Postoperatively,the patient’s respiratory symptoms were relieved,and no signs of recurrence were found during the six-month follow-up.CONCLUSION This article reports a rare case of chronic pulmonary mucormycosis caused by Rhizopus microsporus in a middle-aged male without dysglycemia or immunodeficiency.The patient’s surgical outcome was excellent,reaffirming that surgery remains the cornerstone of pulmonary mucormycosis treatment.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 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.
文摘Nocardiosis is a localized or disseminated infection caused by soil-borne aerobic actinomycetes. Pulmonary nocardiosis is a rare infection mostly occurring in immunocompromised patients.We reported a case of 36 year old immunocompetent non-smoker female patient with no premorbid illness who presented with fever,cough with scanty sputum,hemoptysis,left sided chest pain and exertional dyspnea for two weeks.There was no past history of tuberculosis,diabetes mellitus or steroid therapy.Chest X-ray showed homogenous peripherally based opacity in the left upper zone.Bronchoscopy was done and brushing sent for culture,which showed colonies with features of Nocardia species after 48 hours.Further phenotypic characterization revealed it to be Nocardia otitidiscaviarum.Patient was treated with cotrimaxazole for six months after which complete recovery was evidenced symptomatically and radiologically.We report this case to emphasize the fact that among the Nocardia species,Nocardia otitidiscaviarum as causative agent of pulmonary disease is rarely reported even in immunocompromised individuals.
文摘In order to investigate the immunoactivity of Lycium Barbarum glycopeptide (LBG), the routinely prepared murine splenic lymphocyte suspension was separately added into the samples with different concentrations (500, 100, 10, 1 μg/ml) of LBG as LBG groups. Blank control group in the absence of Lycium Barbarum glycopeptide or ConA and positive control group in the presence of 0.5 ml ConA but in the absence of LBG were created. 0.5 ml LBG samples with different concentrations in combination with 0.5 ml ConA (10 μg/ml) into each well to observe the synergic effects of LBG and ConA as LBG+ConA groups. After incubation for 72 h at 37 ℃, the samples were analyzed by CFSE-labeled cells combined with flow cytometry, and MTT. Flow cytometry revealed that both LBG could enhance the murine splenic lymphocyte proliferative reaction. Combined use of LBG and ConA had synergic effects. MTT demonstrated that sample A could obviously promote the murine splenic lymphocyte proliferative reaction as compared with control group (P<0.01), while sample B could also enhance the lymphocyte proliferation at a high dose. In combination with ConA, sample A had synergic effects at high dose, while sample B showed obviously synergic effects (P<0.05). It was concluded that both samples (A and B) had strong immunocompetence.
文摘Cytomegalovirus enteritis is most usually associated with patients positive for human immunodeficiency virus or immunosuppressed transplant patients. The gastrointestinal tract may be affected anywhere from the esophagus to the colon, but the small bowel involvement is rare. We report a case of cytomegalovirus ileitis in an immunocompetent adult, which was confirmed by histopathologic findings through colonoscopic biopsy.
文摘Herpes simplex esophagitis （HSE） is well documented in immunosuppressed patients. However, it is rare in the immunocompetent host. We present a case of HSE in a 21 year-old healthy lady who was admitted to our unit with dysphagia, odynophagia and chest pain. Clinical examination revealed mild epigastric tenderness and admission bloods including full blood picture, electrolytes and inflammatory markers were normal. She underwent an esophagogastroduodenoscopy （EGD） which revealed severe exudative, well-circumscribed ulcerations in her distal esophagus. Biopsies confirmed severe esophagitis with acute ulceration and subsequent polymerase chain reaction （PCR） confirmed herpes simplex virus （HSV） type 1. Subsequent assessment failed to identify an immune disorder. HSE should be suspected when faced with characteristic endoscopic findings, even if the patient is immunocompetent. When the diagnosis of HSE is confirmed, an immune deficiency should be sought.
文摘AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.
基金Supported by the Ministry of Science and Technology (MOST) of China (No. 2008AA09Z409)
文摘Information regarding immunocompetence of the adaptive immune system （AIS） in zebrafish Danio rerio remains limited. Here, we stimulated an immune response in fish embryos, larvae and adults using lipopolysaccharide （LPS） and measured the upregulation of a number of AIS-related genes （Rag2, AID, TCRAC, IgLC-1, mIg, slg, IgZ and DAB） 3 and 18 h later. We found that all of the genes evaluated were strongly induced following LPS stimulation, with most of them responding at 8 d post fertilization. This confirms that a functional adaptive immune response is present in D. rerio larvae, and provides a window for further functional analyses.
基金Supported by Hunan Provincial Natural Science Foundation of China,No.2022JJ40247,No.2022JJ40256。
文摘BACKGROUND Pulmonary mucormycosis is a rare but life-threatening invasive fungal infection that mostly affects immunocompromised patients.This disease usually develops acutely and progresses rapidly,often leading to a poor clinical prognosis.Chronic pulmonary mucormycosis is highly unusual in immunocompetent patients.CASE SUMMARY A 43-year-old man,who was a house improvement worker with a long history of occupational dust exposure,presented with an irritating cough that had lasted for two months.The patient was previously in good health,without dysglycemia or any known immunodeficiencies.Chest computed tomography revealed a mass in the left lower lobe,measuring approximately 6 cm in diameter,which was suspected to be primary lung carcinoma complicated with obstructive pneumonia.Thoracoscopic-assisted left lower lobectomy was performed,and metagenomic next-generation sequencing detection,along with special pathological staining of surgical specimens,suggested Rhizopus microsporus infection.Postoperatively,the patient’s respiratory symptoms were relieved,and no signs of recurrence were found during the six-month follow-up.CONCLUSION This article reports a rare case of chronic pulmonary mucormycosis caused by Rhizopus microsporus in a middle-aged male without dysglycemia or immunodeficiency.The patient’s surgical outcome was excellent,reaffirming that surgery remains the cornerstone of pulmonary mucormycosis treatment.
