Immunomodulation as a Treatment for Parkinson´s Disease in Current Trials: A Systematic Review and Meta-Analysis

ABSTRACT Background: Immunomodulatory drugs and immunotherapies are being evaluated in clinical trials for the treatment of neuroinflammation, as the latter is an essential mechanism for the development and progression of Parkinson´s disease. Objective: The objective of the study is to review recent evidence on the evaluation of immunomodulators in randomized controlled clinical trials measuring improvement of motor symptoms. Methods: A meta-analysis of Movement Disorder Society-Unified Parkinson´s disease Rating Scale (MDS-UPDRS III) scores extracted from seven articles selected after an online search of PubMed, Cochrane Library, and Clarivate's Web of Science for randomized controlled clinical trials published between 2000 and July 2023 was performed. The selected articles reported clinical trials evaluating the effects of specific immunomodulators or treatments with known effects on the immune system and inflammation. MDS-UPDRS III scores were reported in these studies, and the results of the placebo groups were compared with those of the treatment groups. Results: A total of 590 patients treated with immunomodulators and 622 patients treated with placebo were included. A test for heterogeneity yielded an I2 value > 50%. The mean standard difference for change in MDS-UPDR III score was −0.46 (CI [95%] = −0.90 - −0.02, p < 0.01). No significant differences were found in the change in mean MDS-UPDR III score between the treatment and placebo groups; however, two studies showed a trend toward separation from the mean. Conclusion: The immunomodulatory treatments included in this study showed no efficacy in improving motor symptoms in Parkinson´s disease patients. Further clinical trials with larger patient populations are needed.

Research advances in the immunomodulatory mechanism of galectin-9 and its role in liver diseases / 临床肝胆病杂志

Galectin-9 （Gal-9） is a member of the galectin family that can specifically recognize and bind to galactosides. Recent studies have shown that Gal-9 is highly expressed in the liver and can help to maintain intrahepatic immune homeostasis and perform biological functions in various liver diseases. This article reviews the immunomodulatory functions of Gal-9 and its role in different liver diseases. Studies have shown that Gal-9 has important biological functions in different liver diseases through multiple pathways. Research on the specific immunomodulatory mechanisms and functions of Gal-9 may help to discover the therapeutic role of Gal-9 in liver diseases.

Advances in mesenchymal stem cells therapy for tendinopathies / 中华创伤杂志(英文版)

Tendinopathies are chronic diseases of an unknown etiology and associated with inflammation. Mesenchymal stem cells (MSCs) have emerged as a viable therapeutic option to combat the pathological progression of tendinopathies, not only because of their potential for multidirectional differentiation and self-renewal, but also their excellent immunomodulatory properties. The immunomodulatory effects of MSCs are increasingly being recognized as playing a crucial role in the treatment of tendinopathies, with MSCs being pivotal in regulating the inflammatory microenvironment by modulating the immune response, ultimately contributing to improved tissue repair. This review will discuss the current knowledge regarding the application of MSCs in tendinopathy treatments through the modulation of the immune response.

The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells / 中华创伤杂志(英文版)

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Application of mesenchymal stem cell therapy in kidney transplantation: a continued story / 器官移植

Immunosuppressant is one of the main preventive measures for rejection after organ transplantation, whereas it may reduce the host response capability to pathogens and increase the risk of infection. In recent years, the application of mesenchymal stem cell (MSC) therapy in the field of solid organ transplantation has attracted widespread attention. Preclinical studies have shown that MSC therapy may prolong the survival time of transplant kidney, induce immune tolerance, accelerate the repair of acute kidney injury and promote the recovery of renal function. Clinical trials have confirmed the safety, tolerance and effectiveness of MSC therapy. Consequently, general characteristics, immunomodulation and tissue repair function of MSC, and the application of MSC in clinical trials of kidney transplantation were reviewed, the unresolved issues were briefly discussed and the prospects for subsequent research were predicted, aiming to provide reference for promoting the application of MSC therapy in clinical kidney transplantation.

Effects of Ophiopogonis Root Decoction on a mouse model of idiopathic pulmonary fibrosis based on PD-1/PD-L1 signaling pathway / 中成药

AIM To investigate the effects of Ophiopogonis Root Decoction on bleomycin(BLM)-induced idiopathic pulmonary fibrosis(IPF)in mice and to explore its metabolic modulation of immunity.METHODS The IPF mouse model was constructed by tracheal drip injection of BLM,and the mice were randomly divided into the control group,the model group,the pirfenidone group(0.3 g/kg)and the high,medium and low dose groups of Ophiopogonis Root Decoction(18,9,4.5 g/kg).HE and Masson staining,ELISA,flow cytometry and immunohistochemistry were used to detect the histopathological changes of the lung,the levels of Collagen I,HYP and TGF-β1,the proportion of PD-1+ CD4+T cells in plasma,and the expressions of p-STAT3,PD-1,PD-L1 and IL-17A in lung tissue,respectively.RESULTS Compared with the control group,the model group displayed significantly higher level of lung coefficients(P<0.01),more severe pulmonary inflammatory cell infiltration and collagen fiber deposition,and increased pulmonary fibrosis score(P<0.01),increased levels of Collagen I,HYP and TGF-β1(P<0.01),increased proportion of PD-1+ CD4+ T cells in plasma(P<0.01),increased pulmonary expression of p-STAT3,PD-1,PD-L1 and IL-17A(P<0.01).Compared with the model group,the Ophiopogonis Root Decoction groups shared lower levels of lung coefficients(P<0.05),less pulmonary inflammatory cell infiltration and collagen fiber deposition,decreased pulmonary fibrosis score(P<0.05),decreased levels of Collagen I,HYP and TGF-β1(P<0.05),decreased proportion of PD-1+ CD4+T cells in plasma(P<0.05),and decreased pulmonary expression of p-STAT3,PD-1,PD-L1,and IL-17A(P<0.05).CONCLUSION Ophiopogonis Root Decoction can significantly reduce extracellular matrix(ECM)deposition and curb the progression of IPF via inhibition of STAT3/PD-1/PD-L1 immunomodulatory signaling pathway.

Exploration the Immune Regulatory Mechanism of Hedysari Radix Based on Network Pharmacology,Molecular Dynamics,and UPLC-MS/MS / 中药新药与临床药理

Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.

Anti-metastatic Pharmacology Based on Tumor Microenvironment Regulation： A Review / 中国实验方剂学杂志

Tumor metastasis is the major cause of death for tumor patients and the key bottleneck of clinical treatment. In recent years， basic and clinical studies have recognized that tumor microenvironment （TME） is highly correlated with tumor metastasis， which provides hope for anti-metastatic drug development and clinical treatment. At present， the mainstream studies on TME represented by immune checkpoint inhibitors （ICIs） mainly focus on the rectification of immune function of T cells and B cells. However， a large number of studies have shown that the significance of other members of TME for tumor metastasis cannot be ignored， which greatly reflects the progress of anti-metastatic research based on TME regulation. This review focused on tumor metastasis， summarized the mechanism of action of non-T and non-B immune cells ［tumor-associated macrophages （TAMs） and tumor-associated neutrophils （TANs）］ and non-immune members ［vascular endothelial cells （ECs）， tumor-associated fibroblasts （CAFs）， and blood platelet］ in the process of tumor metastasis in TME based on the literature over the recent five years， and explored their key value in the treatment of metastasis. At the treatment level， this review focused on the perspective of the integration of frontier and traditional methods and took the functional homeostasis remodeling of TME as the entry point to summarize the activity and mechanism of traditional Chinese medicine （TCM） regulation of non-T and non-B immune cells and non-immune members and highlight its advantages and characteristics in clinical intervention of metastasis. This review helps to break through the limitations of over-reliance on T and B immune cells in anti-metastatic research， make the research rely on a wider range of cell groups， explore the potential value of TME in anti-metastatic drug intervention， and enrich the idea and strategy of understanding the anti-metastatic pharmacological activity. The review is also expected to provide a broader vision for the research and development of new anti-metastatic drugs.

Advances in methods and techniques for the study of polysaccharide in vivo processes and immunomodulatory mechanisms / 药学学报

In recent years, polysaccharides have received much attention because of their high safety and good immunological activity. The study of polysaccharide in vivo process is a key scientific problem that needs to be solved for polysaccharide drug development. Some progress has been made in the field of polysaccharide pharmacokinetics and immunomodulation. However, due to the lack of both chromogenic and light-absorbing groups and the complex molecular structure of polysaccharides, the in vivo processes and immunomodulatory mechanisms of polysaccharides have been slow to be investigated. The effective combination of multiple techniques can break the bottleneck of difficult tracing and unknown immunomodulatory mechanism of polysaccharides in vivo, and promote the development and utilization of polysaccharides. In this paper, we systematically summarize the key techniques in the study of polysaccharide in vivo processes and immunomodulatory mechanisms in order to provide technical references and research ideas for the study of polysaccharide in vivo processes and immunomodulatory mechanisms.

Transplantation of menstrual blood-derived endometrial stem cells allevi-ates chemotherapy-induced intestinal injury and flora imbalance in mice through immunomodulation / 中国病理生理杂志

AIM:To investigate the therapeutic effect of menstrual blood-derived endometrial stem cells(MenSCs)on chemotherapy-induced intestinal mucositis and flora disorders in mice,and to explore the potential mecha-nism.METHODS:The mice were randomly divided into 3 groups including normal treatment,cisplatin(Cis)treatment and Cis+MenSC treatment,with 10 mice in each group.To induce intestinal mucositis,the mice were treated with Cis(2 mg·kg-1·d-1)by intraperitoneal injection for 5 consecutive days.Control mice for normal group were received equal vol-umes of normal saline.For Cis+MenSC treatment,MenSCs(1×106)was transplanted into the mice of Cis treated mice through tail vein.The performances and weight changes of mice were examined during the experiment.After the treat-ment,the small intestine and colon were isolated for subsequent HE staining,the ratio of F4/80 and IL-6 positive cells in small intestine were detected by immunohistochemical staining,and the expression of tight junction,inflammation and apoptosis related proteins was detected by Western blot.16S rDNA amplicon sequencing was performed to detect the diver-sity and richness of intestinal flora in mice.RESULTS:Compared to the Cis group,the MenSCs-treated mice showed sig-nificantly increased body weight,relieved intestinal lymphocytes infiltration,alleviated intestinal villous edema,and or-derly arranged glands in intestinal tissues.Further analysis indicated that MenSCs transplantation significantly up-regulat-ed the expression of intestinal tight junction related proteins ZO-1 and occludin in Cis-treated mice(P＜0.05).Subse-quently,MenSCs transplantation significantly inhibited the macrophages infiltration in intestinal tissues(P＜0.01),down-regulated the expression of pro-inflammatory factors IL-1 and IL-6 and pro-apoptotic protein Bax(P＜0.01),while up-regu-lated anti-inflammatory factor IL-10 and anti-apoptotic protein Bcl-2(P＜0.01).Additionally,further microflora sequenc-ing indicated that MenSCs transplantation prevented mice from Cis-induced intestinal flora disorder,and significantly re-duced the abundance of harmful bacteria such as isenbergiella tayi and Anaerotruncus colihominis(P＜0.01).At the same time,the abundance of beneficial bacteria Lactobacillus apodemi was increased(P＜0.05),thereby restoring the composi-tion and function of healthy intestinal flora.CONCLUSION:MenSCs transplantation alleviates the chemotherapy-in-duced damage of intestinal structure,relieves the symptoms of chemotherapy-induced mucositis and restores the homeosta-sis of intestinal flora in mice.

Adiponectin restores the obesity-induced impaired immunomodulatory function of mesenchymal stromal cells via glycolytic reprogramming

Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells (MSC). However, it remains unclear what drives the compromised potency of obese MSC. In this study, we examined the involvement of adiponectin, an adipose tissue-derived hormone, in obesity-induced impaired therapeutic function of MSC. Diet-induced obesity leads to a decrease in serum adiponectin, accompanied by impairment of survival and immunomodulatory effects of adipose-derived MSC (ADSC). Interestingly, priming with globular adiponectin (gAcrp) improved the immunomodulatory potential of obese ADSC. Similar effects were also observed in lean ADSC. In addition, gAcrp potentiated the therapeutic effectiveness of ADSC in a mouse model of DSS-induced colitis. Mechanistically, while obesity inhibited the glycolytic capacity of MSC, gAcrp treatment induced a metabolic shift toward glycolysis through activation of adiponectin receptor type 1/p38 MAPK/hypoxia inducible factor-1α axis. These findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.

Osteomielite maxilar associada ao COVID-19: mucormicose ou não? Uma série de casos / Maxillary osteomyelitis associated with COVID-19: mucormycosis or not? A series of cases

Aim: A series of cases have been presented involving the oral cavity focusing on the presentation, diagnosis and treatment of mucormycosis that can form a basis for successful therapy. Background: The management of severe coronavirus disease (COVID-19) in conjunction with comorbidities such as diabetes mellitus, hematological malignancies, organ transplants, and immunosuppression have led to a rise of mucormycosis which is an opportunistic infection. Cases Description: The various forms that have been enlisted till date are rhino-cerebral, rhino-orbital, gastrointestinal, cutaneous, and disseminated mucormycosis. From the dentistry and maxillofacial surgery perspective, the cases depicting extension of mucormycosis into the oral cavity have been less frequently recorded and thus, require a detailed study. The patients that reported to our private practice had non-tender swelling, draining sinuses and mobility of teeth. A similarity was observed in the clinical signs both in osteomyelitis and mucormycosis. Thus, a histopathological examination was used to establish the definitive diagnosis. Conclusion: Mucormycosis is a life threatening pathology that requires intervention by other branches to make an early diagnosis and commence the treatment. The characteristic ulceration or necrosis is often absent in the initial stage and thus, histopathological examination and radiographic assessment are required to formulate a definitive diagnosis. Early intervention is a necessity to avoid morbidity. The treatment involves surgical debridement of the necrotic infected tissue followed by systemic antifungal therapy. Mucormycosis has recently seen a spike in its prevalence, post the second-wave of coronavirus pandemic in India. It was seen commonly in patients with compromised immunity, diabetes mellitus, hematological malignancies, or on corticosteroid therapy. Mucormycosis invading the palate mostly via maxillary sinus has been less frequently described. In the post-COVID era the features associated with mucormycosis involving oral cavity, should warrant a possible differential diagnosis and managed appropriately. (AU)

Objetivo: Apresentar uma série de casos com enfâse na apresentação, diagnóstico e tratamento da mucormicose oral, assim como uma revisão sistemática que sirva como base para estabelecimento de terapias de sucesso. Introdução: A forma severa da infecção por coronavirus (COVID-19) associada a diabetes mellitus, doenças hematológicas malignas, transplante de órgãos e imunossupressão levaram a um aumento das infecções oportunistas de mucormicose. Descrição dos Casos: As diversas apresentações clínicas que foram descritas até o momento são a rinocerebral, rino-orbital, gastrointestinal, cutânea e mucormicose disseminada. No que concerne a odontologia e a cirurgia maxillofacial, os casos que apresentam extensão de mucormicose para cavidade oral tem sido menos reportados e assim requerem mais estudos. Os pacientes que compareceram a nossa clínica apresentavam aumento de volume endurecido, drenagem de fluidos dos seios maxilares e mobilidade dentária. Clinicamente tanto a osteomielite quanto a mucormicose apresentaram-se de forma semelhante. Assim, análise histopatológica foi utilizada para estabelecimento do diagnóstico definitivo. Conclusão: A mucormicose é uma patologia grave que requer intervenção precoce para estabelecimento do tratamento. A ulceração e necrose características usualmente estão ausentes nos estágios iniciais da lesão, assim análise histopatológica e radiográfica são necessárias para o diagnóstico final. Intervenção precoce é necessária para diminuir a morbidade. O tratamento envolve o debridamento cirúrgico da área necrosada seguida de terapia antifúngica sistêmica. Recentemente, houve um aumento nos casos de mucormicose, após a Segunda onda da pandemia de COVID-19 na índia. Os casos acometiam principalmente pacientes imunocomprometidos, com diabetes mellitus, doenças hematológicas malignas e em uso de corticosteróides. A mucormicose invadindo o palato pelos seios maxilares foi raramente descrita. Na era pós-COVID a mucormicose envolvendo a cavidade oral deve entrar no painel de diagnósticos diferenciais para que o tratamento adequado possa ser instituído precocemente.(AU)

Reshaping neuroimmunology: diagnosis and treatment in the era of precision medicine / Remodelando a neuroimunologia: diagnóstico e tratamento na era da medicina de precisão

Abstract Precision medicine has revolutionized the field of neuroimmunology, with innovative approaches that characterize diseases based on their biology, deeper understanding of the factors leading to heterogeneity within the same disease, development of targeted therapies, and strategies to tailor therapies to each patient. This review explores the impact of precision medicine on various neuroimmunological conditions, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), optic neuritis, autoimmune encephalitis, and immune-mediated neuropathies. We discuss advances in disease subtyping, recognition of novel entities, promising biomarkers, and the development of more selective monoclonal antibodies and cutting-edge synthetic cell-based immunotherapies in neuroimmunological disorders. In addition, we analyze the challenges related to affordability and equity in the implementation of these emerging technologies, especially in situations with limited resources.

Resumo A medicina de precisão está revolucionando o campo da neuroimunologia, com uma abordagem inovadora caracterizada pela classificação de doenças com base em sua biologia, compreensão mais profunda dos fatores que levam à heterogeneidade dentro da mesma doença, desenvolvimento de terapias com alvos específicos e estratégias para adaptar as terapias a cada paciente. Esta revisão explora o impacto da medicina de precisão em várias condições neuroimunológicas, incluindo esclerose múltipla (EM), distúrbio do espectro da neuromielite óptica (NMOSD), doença associada ao anticorpo anti-glicoproteína da mielina do oligodendrócito (MOGAD), neurites ópticas, encefalites autoimunes e neuropatias imunomediadas. Discutimos avanços na subclassificação de doenças, reconhecimento de novas entidades, biomarcadores promissores e desenvolvimento de anticorpos monoclonais mais seletivos e imunoterapias de ponta baseadas em células sintéticas para as condições acima. Além disso, analisamos os desafios relacionados com acessibilidade e equidade na implementação dessas tecnologias emergentes, especialmente em ambientes com recursos limitados.

Humoral and Cellular Immunology in Human Prostate Cancer: Plasma Cells and T and B Lymphocytes / Inmunología Humoral y Celular en el Cáncer de Próstata Humano: Células Plasmáticas y Linfocitos T y B

SUMMARY: In solid and malignant tumors, innate and adaptive immunity are combined in antitumor responses. This study aimed to analyze the activation of plasma cells and the correlation between the infiltration of B and T lymphocytes with the degree of malignancy or Gleason grade in human prostate biopsies diagnosed with cancer. Prostate cancer biopsies were obtained from the Clinical Hospital of Universidad de Chile (n=70), according to the bioethical norms of the institution. Histological sections of 5µm thickness were processed for immunohistochemistry with primary antibodies against BL and total TL (HRP/DAB). Recognition and quantification were performed under a Leica DM750 optical microscope. Microsoft Excel and GraphPad software were used for the statistical study. Correlation coefficient (Pearson) and mean comparison tests (Kruskal-Wallis and Dunn) and p≤ 0.05 were developed. B and T lymphocyte populations were inversely interregulated in prostate cancer (Gleason) (r= -0.46). Their relationship with Gleason grade is variable according to lymphocyte type (LB vs. Gleason r= -0.0.47 and LT vs. Gleason r= -0.21). Histological diagnosis of prostate cancer correlates with a predominance of LT. The malignancy of the pathology correlates with a predominance of LTs, according to the Gleason grade. The increased knowledge of B and T lymphocyte infiltration and plasma cell activation could be used to better target clinical trials on treatments based on immune system responses. Immunotherapy could be a new paradigm to apply better antitumor therapy strategies.

En tumores sólidos y malignos, la inmunidad innata y adaptativa se combinan en respuestas antitumorales. Este estudio tuvo como objetivo analizar la activación de células plasmáticas y la correlación entre la infiltración de linfocitos B y T con el grado de malignidad o grado de Gleason en biopsias de próstata humana diagnosticadas con cáncer. Las biopsias de cáncer de próstata se obtuvieron del Hospital Clínico de la Universidad de Chile (n=70), de acuerdo con las normas bioéticas de la institución. Secciones histológicas de 5 µm de espesor fueron procesadas para inmunohistoquímica con anticuerpos primarios contra LB y LT total (HRP/DAB). El reconocimiento y las cuantificaciones se realizaron bajo un microscopio óptico Leica DM750. Para el estudio estadístico se utilizaron los programas Microsoft Excel y GraphPad. Se desarrollaron pruebas de coeficiente de correlación (Pearson) y comparación de medias (Kruskal-Wallis y Dunn) y p≤ 0.05. Los resultados muestran que las poblaciones de linfocitos B y T están inversamente interreguladas en el cáncer de próstata (r= -0,4578). Su relación con el grado de Gleason es variable según el tipo de linfocito (LB vs Gleason r= -0,47* y LT vs Gleason r= -0,21). Se concluye que la malignidad del cáncer de próstata se correlaciona con un predominio de LT, versus el grado de Gleason. El mayor conocimiento de la infiltración de linfocitos B y T y la activación de células plasmáticas podría aprovecharse para una mejor orientación de ensayos clínicos en tratamientos basados en las respuestas del sistema inmunitario. La inmunoterapia podría ser un nuevo paradigma para aplicar mejores estrategias de terapias antitumorales.

The Role of MicroRNAs in the Pathogenesis of Chagas Disease

Abstract Chagas disease (CD) is caused by the protozoan Trypanosoma cruzi and affects about six to seven million individuals worldwide. The distribution of cases is concentrated mainly throughout Latin America, especially in rural areas. This study aims to evaluate microRNAs (miRNAs) as indicators in CD diagnosis for possible contributions to its management. This is a literature review study, carried out in the PubMed, SciELO, Bireme Library, NCBI, Science Direct, and Embase databases, through which a total of 12 articles were included for qualitative analysis. The discussion of this review was based on the thematic axes regarding the modulation of T. cruzi in the immune system and the expression of miRNAs, their production and action, the modulation mechanism of host gene expression, how they act as biomarkers, the importance of miRNAs in the diagnosis of CD, and how their regulation occurs in Chronic Chagas Cardiomyopathy (CCC). Moreover, T. cruzi infection is associated with the downregulation of several miRNAs, which directly related to the findings of hypertrophy and fibrosis. When quantified, these could be used as consistent indicators for CD to support the diagnosis of patients with CD complications, as well as a possible therapeutic target. However, the need for clinical studies that evaluate the usefulness of this biomarker in humans is emphasized, considering that in the present study, only experimental in vitro studies were evaluated, reflecting a lack of studies with practical applicability.

A confirmed case of macrophage activation syndrome secondary to spotted fever rickettsiosis: Response to immunomodulation in a pediatric patient in northeastern, Mexico

An 8-year-old girl with a rash and high-grade fever for 6 days arrived at the emergency room. She had an erythematous macular rash on the face, trunk, arms, and legs. Further interrogation called attention to the presence of close contact with stray dogs. Her town had been recognized as a site of a rickettsiosis outbreak in the past year. Spotted fever rickettsiosis was suspected, and doxycycline treatment was initiated. Macrophage activation syndrome (MAS) secondary to Rickettsia rickettsii infection was diagnosed according to the Hemophagocytic lymphohistiocytosis and EULAR/PRINTO/PRES 2016 criteria. As there are no clear guidelines on the treatment of MAS secondary to R. rickettsii. the course of action taken by the pediatric intensive care unit team was to avoid disseminated intravascular coagulopathy and treat MAS, both life-threatening conditions. Directed therapy with high doses of methylprednisolone and intravenous immunoglobulin therapy was initiated. The patient recovered, regaining her functional state before the illness. Few articles have described the association between MAS and rickettsiosis, an illness with high mortality, which makes it paramount to detect and treat promptly.

Actividad fagocítica y toxicidad del extracto acuoso de Schinus molle L. sobre Mus musculus BALB/c / Phagocytic activity and toxicity of the aqueous extract of Schinus molle L. on Mus musculus BALB/

Introducción: La medicina tradicional podría ser una alternativa segura para potenciar la inmunidad de pacientes inmunocomprometidos propensos a infecciones recurrentes. Objetivo: Evaluar la actividad fagocítica y toxicidad in vivo del extracto acuoso de Schinus molle L. en Mus musculus BALB/c. Material y Métodos: Estudio experimental que utilizó una dosis única de extracto acuoso de hojas de Schinus molle de 2000 mg/kg. La fagocitosis in vivo se determinó en 10 ejemplares de M. musculus BALB/c que cumplieron criterios de inclusión y exclusión, distribuidos aleatoria y equitativamente en los grupos control y experimental. Los especímenes del grupo experimental fueron inoculados vía intraperitoneal con 0,5 ml de suspensión de Staphylococcus aureus y 0,5 ml del extracto acuoso. Los del grupo control con 0,5 ml del mismo inóculo bacteriano y 0,5 ml de solución salina estéril. La toxicidad del extracto se evaluó por el método de las clases de toxicidad aguda en 12 ejemplares de ratones con las mismas características y cumpliendo los mismos criterios aplicados en la evaluación de la fagocitosis in vivo. Resultados: El 57,1 % de los macrófagos expuestos al extracto acuoso de S. molle presentaron importante actividad fagocítica, encontrándose una media de 21 bacterias fagocitadas por macrófago. No se evidenciaron significativamente signos ni síntomas de toxicidad en los especímenes durante los 14 días de experimentación. Conclusiones: El extracto acuoso de S. molle incrementó significativamente la fagocitosis in vivo de los macrófagos peritoneales de M. musculus BALB/c, sin evidencia de clínica de toxicidad y en ausencia de mortalidad(AU)

Introduction: Traditional medicine could be a safe alternative to enhance the immunity of immunocompromised patients prone to recurrent infections. Objective: To evaluate the phagocytic activity and in vivo toxicity of the aqueous extract of Schinus molle L. on Mus musculus BALB/c. Material and Methods: Experimental study that used a single dose of aqueous extract of Schinus molle leaves of 2000 mg/kg. In vivo phagocytosis was determined in 10 specimens of M. musculus BALB/c that met the inclusion and exclusion criteria, which were randomly and equally distributed in the control and experimental groups. The specimens of the experimental group were inoculated intraperitoneally with 0.5 ml of Staphylococcus aureus suspension and 0.5 ml of the aqueous extract. Those of the control group were inoculated with 0.5 ml of the same bacterial inoculum and 0.5 ml of sterile saline solution. The toxicity of the extract was evaluated by the method of the acute toxicity classes in 12 specimens of mice with the same characteristics that fulfilled the same criteria applied in the evaluation of phagocytosis in vivo. Results: The results demonstrate that 57.1% of the macrophages exposed to the aqueous extract of S. molle showed significant phagocytic activity, finding an average of 21 phagocytosed bacteria per macrophage. No significant signs or symptoms of toxicity were evidenced in the specimens during the 14 days of experimentation. Conclusions: The aqueous extract of S. molle significantly increased in vivo phagocytosis of peritoneal macrophages from M. musculus BALB/c, without clinical evidence of toxicity and in the absence of mortality(AU)

Antagonism of Lentinan on sodium arsenite induced hepatotoxicity in mice / 公共卫生与预防医学

Objective To explore the intervention effects of lentinan on sodium arsenite (SA) induced hepatotoxicity in mice. Methods Healthy male C57BL/6 mice were used as experimental subjects and divided into 4 groups, namely control group, SA treatment group, lentinan intervention + SA exposure group, and lentinan intervention control group. The mice were given oral SA (10.0 mg/kg.bw, once every other day) for 14 days, and then the liver tissues and serum samples were collected. Hematoxylin-eosin (HE) was used to evaluate the characteristics of hepatic pathological damage. Enzyme-linked immunosorbent assay (ELISA), Flow Cytometry (FC) and Western-blotting (WB) were used to detect the levels of hepatic function, oxidative stress, CD4+ type 17 helper T cells (Th17), and inflammatory cytokines. Results Compared with the control group, the arsenic exposure group showed obvious hepatic pathological injury and increased levels of serum ALT (8.78±0.76 vs 5.47±0.49) and AST (12.42±1.87 vs 7.14±0.57), FC experiments showed that the Th17 content in liver tissues increased (67.70±4.94 vs 7.36±1.50), and ELISA showed that the antioxidant GSH content decreased (593.40±23.25 vs 730.94±30.81), and the levels of MDA (74.56±7.63 vs 49.90±6.42) and proinflammatory cytokines IL-17A (162.48±10.75 vs 118.53±7.92) and IL-1β (512.50±24.78 vs 462.48±22.15) increased in hepatic tissues (P < 0.05). Compared with the arsenic exposure group, the lentinan showed a significant antagonistic effect after intervention (P < 0.05). Compared to SA exposure group, WB analysis showed that compared with the arsenic exposure group, the expression levels of IL-17A (0.47±0.08 vs 0.89±0.11) and NLRP3 inflammasome (0.80±0.09 vs 1.09±0.16) in the liver tissues of the lentinan intervention group were significantly decreased (P < 0.05). Conclusion Lentinan alleviates SA-induced hepatic injury in mice, which may be mediated through the inhibition of Th17-IL-17A inflammatory signaling.

Immune regulation mechanism of Saposhnikoviae Radix polysaccharide based on zebrafish model / 中国中药杂志

The immunomodulatory effect of Saposhnikoviae Radix polysaccharide(SRP) was evaluated based on the zebrafish mo-del, and its mechanism was explored by transcriptome sequencing and real-time fluorescence-based quantitative PCR(RT-qPCR). The immune-compromised model was induced by navelbine in the immunofluorescence-labeled transgenic zebrafish Tg(lyz: DsRed), and the effect of SRP on the density and distribution of macrophages in zebrafish was evaluated. The effect of SRP on the numbers of macrophages and neutrophils in wild-type AB zebrafish was detected by neutral red and Sudan black B staining. The content of NO in zebrafish was detected by DAF-FM DA fluorescence probe. The content of IL-1β and IL-6 in zebrafish was detected by ELISA. The differentially expressed genes(DEGs) of zebrafish in the blank control group, the model group, and the SRP treatment group were analyzed by transcriptome sequencing. The immune regulation mechanism was analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment, and the expression levels of key genes were verified by RT-qPCR. The results showed that SRP could significantly increase the density of immune cells in zebrafish, increase the number of macrophages and neutrophils, and reduce the content of NO, IL-1β, and IL-6 in immune-compromised zebrafish. The results of transcriptome sequencing analysis showed that SRP could affect the expression level of immune-related genes on Toll-like receptor pathway and herpes simplex infection pathway to affect the release of downstream cytokines and interferon, thereby completing the activation process of T cells and playing a role in regulating the immune activity of the body.

Let -7i : A key player and a promising biomarker in diseases / 中南大学学报(医学版)

MicroRNAs (miRNAs) are endogenous non-coding single-stranded small RNAs that regulate gene expression by recognizing homologous sequences and interfering with transcriptional, translational or epigenetic processes. MiRNAs are involved in a variety of disease processes, and regulate the physiological and pathological status of diseases by modulating target cell activity, migration, invasion, apoptosis, autophagy and other processes. Among them, let-7i is highly expressed in various systems, which participates in the process of tumors, cardiovascular and cerebrovascular diseases, fibrotic diseases, inflammatory diseases, neurodegenerative diseases and other diseases, and plays a positive or negative regulatory role in these diseases through different signal pathways and key molecules. Moreover, it can be used as an early diagnosis and prognostic marker for a variety of diseases and become a potential therapeutic target. As a biomarker, let-7i is frequently tested in combination with other miRNAs to diagnose multiple diseases and evaluate the clinical treatment or prognosis.