A mathematic equation derived from host-pathogen interactions elucidates the significance of integrating modern medicine with traditional Chinese medicine to treat infectious diseases / 中西医结合学报

The prognosis of infectious diseases is determined by host-pathogen interactions. Control of pathogens has been the central dogma of treating infectious diseases in modern medicine, but the pathogen-directed medicine is facing significant challenges, including a lack of effective antimicrobials for newly emerging pathogens, pathogen drug resistance, and drug side effects. Here, a mathematic equation (termed equation of host-pathogen interactions, HPI-Equation) is developed to dissect the key variables of host-pathogen interactions. It shows that control of pathogens does not necessarily lead to host recovery. Instead, a combination of promoting a host's power of self-healing and balancing immune responses provides the best benefit for host. Moreover, the HPI-Equation elucidates the scientific basis of traditional Chinese medicine (TCM), a host-based medicine that treats infectious diseases by promoting self-healing power and balancing immune responses. The importance of self-healing power elucidated in the HPI-Equation is confirmed by recent studies that the tolerance mechanism, which is discovered in plants and animals and conceptually similar to self-healing power, improves host survival without directly attacking pathogens. In summary, the HPI-Equation describes host-pathogen interactions with mathematical logic and precision; it translates the ancient wisdoms of TCM into apprehensible modern sciences and opens a new venue for integrating TCM and modern medicine for a future medicine. Sun J. A mathematic equation derived from host-pathogen interactions elucidates the significance of integrating modern medicine with traditional Chinese medicine to treat infectious diseases. J Integr Med. 2023; 21(4):324-331.

¿Es posible que nuestra generación enfrente una nueva pandemia causada por otro Coronavirus? / Is it possible that our generation will deal a new pandemic caused by another Coronavirus?

RESUMEN La actual pandemia de COVID-19 fue inducida por la emergencia de un coronavirus en un animal reservorio. De esta manera, es de gran importancia conocer como ocurre la evolución de estos agentes virales en la naturaleza. En este artículo, son presentados los principales mecanismos asociados a la evolución de los coronavirus considerando las especies de animales que actúan como reservorios o huéspedes evolutivos, los mecanismos genéticos virales arrollados en la generación de variantes virales y la contribución de las acciones humanas que puedan generar nuevos coronavirus recombinantes con potencial pandémico. Considerando los puntos discutidos en este artículo, concluimos que la generación de nuevos coronavirus podrá ser evitada con la implementación de políticas públicas que propongan acciones de salud única y así solo habrá salud humana habiendo salud ambiental y salud animal.

ABSTRACT The current COVID-19 pandemic was induced by the emergence of a coronavirus from an animal as a reservoir. Thus, it is of great importance to know how the evolution of these viral agents occurs in the nature. In this article, the main mechanisms associated with the evolution of coronaviruses were presented, indicating the animal species that act as reservoirs or evolutionary hosts, the viral genetic mechanisms involved in the generation of viral variants, the contribution of human actions to generate recombinant coronaviruses with pandemic potential. From the points discussed in the article, we conclude that the generation of new coronaviruses can be avoided with the implementation of public policies that propose health actions and thus there will only be human health if there is environmental health and animal health.

Genetic diversity of Trypanosoma cruzi strains isolated from chronic chagasic patients and non-human hosts in the state of São Paulo, Brazil

BACKGROUND Trypanosoma cruzi shows an exuberant genetic diversity. Currently, seven phylogenetic lineages, called discrete typing units (DTUs), are recognised: TcI-TcVI and Tcbat. Despite advances in studies on T. cruzi and its populations, there is no consensus regarding its heterogeneity. OBJECTIVES This study aimed to perform molecular characterisation of T. cruzi strains, isolated in the state of São Paulo, to identify the DTUs involved and evaluate their genetic diversity. METHODS T. cruzi strains were isolated from biological samples of chronic chagasic patients, marsupials and triatomines through culture techniques and subjected to molecular characterisation using the fluorescent fragment length barcoding (FFLB) technique. Subsequently, the results were correlated with complementary information to enable better discrimination between the identified DTUs. FINDINGS It was possible to identify TcI in two humans and two triatomines; TcII/VI in 19 humans, two marsupials and one triatomine; and TcIII in one human host, an individual that also presented a result for TcI, which indicated the possibility of a mixed infection. Regarding the strains characterised by the TcII/VI profile, the correlation with complementary information allowed to suggest that, in general, these parasite populations indeed correspond to the TcII genotype. MAIN CONCLUSIONS The TcII/VI profile, associated with domestic cycles and patients with chronic Chagas disease, was the most prevalent among the identified DTUs. Furthermore, the correlation of the study results with complementary information made it possible to suggest that TcII is the predominant lineage of this work.

Immune system: development and acquisition of immunological competence

Abstract Objectives: To describe the ontogeny of the immune system and the adaptive mechanisms of the immune system in the neonatal period, with an emphasis on transplacental antibody transport and breastfeeding. Source of data: Non-systematic literature review in the PubMed database. Summary of the findings: The last two decades have witnessed a great advance in the knowledge of the immune system since conception. Several investigation tools have provided insight on phenomena that were previously inadequately understood. Still expanding, the functional and molecular investigation of various aspects of the immune system will make it possible to understand how intra-uterus maternal-fetal exchanges, the maternal microbiota interacting with the fetus and newborn, and the acquisition of immunological competence occur in healthy and disease scenarios. Conclusions: In-depth knowledge of the development of the immune system and of the adaptive mechanisms that allow a safer transition to the extrauterine environment are fundamental components of optimizing maternal and young infant vaccination, as well as the strategies associated with full postnatal development, and the early diagnosis and treatment of innate errors of immunity.

Influenza needs an approach as a "one health" problem in Colombia / Influenza requiere un manejo bajo la perspectiva de "una salud" en colombia

RESUMEN La influenza es una infección viral de importancia y distribución mundial, cuyo agente causal es el Alfainfluenzavirus o influenza virus tipo A (IAV), el cual se caracteriza por poseer un genoma de tipo ssRNA segmentado, aspecto que le confiere una alta variabilidad y capacidad recombinante. Esto, sumado al amplio rango de huéspedes susceptibles y la posibilidad de transmisión entre especies, se constituye en un reto tanto para la salud humana como para la animal. El IAV es capaz de infectar una amplia variedad de huéspedes, incluyendo múltiples especies de aves y mamíferos, tanto domésticas como salvajes y al humano, así como a reptiles y anfibios, entre otros. Dentro de los Alphainfluenzavirus se reconocen 16 subtipos de Hemaglutinina (HA) y nueve de Neuraminidasa (NA), siendo su principal reservorio las aves silvestres acuáticas. Adicionalmente, se han reconocido dos nuevos subtipos en murciélagos (H17-18 y N10-11), los cuales se han denominado Influenza-like virus. Teniendo en cuenta lo anterior y conocedores de la riqueza en biodiversidad que posee Colombia, país en el que está demostrada la circulación del virus en cerdos y en humanos y hay resultados preliminares de la presencia de Orthomyxovirus en murciélagos, es imperativo estudiar y conocer los IAV circulantes en el medio, establecer factores de riesgo y analizar el efecto que han tenido y seguirán teniendo las condiciones asociadas al cambio climático, los factores sociodemográficos y el papel de diferentes especies en la ecología de este agente viral. Todo lo anterior bajo el contexto de "Una Salud" en la infección por IAV.

ABSTRACT Influenza is an important viral disease of worldwide distribution. It is caused by the Alfainfluenzavirus or influenza virus type A (IAV). A segmented ssRNA genome in the influenza viruses confers high variability and reassortment capability to the virus. That and the broad range of susceptible hosts, along with the possibility of inter-species transmission, represents a challenge to human and animal health. The IAV is able to infect a large variety of hosts such as several wild and domestic avian and mammalian species, including humans, as well as reptiles and amphibians, among others. There are 16 hemagglutinin (HA) and nine neuraminidase (NA) subtypes recognized until know, whose main reservoir are the wild aquatic birds. In addition, two new subtypes (H17-18 and N10-11) have been recognized in bats, and these have been designated as influenza-like viruses. Taking this into account and knowing the richness of biodiversity in Colombia, there is an imperative need to study and to know about the IAV circulating in the field in order to establish risk factors and to analyze the past, the current and the future effect that climate change, sociodemographic factors and the role that different species could play in the eco-biology of this viral agent. This should be considered under the one health concept of influenza virus infection as a whole, considering the fact that Colombia is a country in which the circulation of IAV has been demonstrated in the swine and human population and there are preliminary results of the presence of Orthomyxovirus in bats.

Detection of autophagy in peripheral CD4+ T lymphocytes and skin lesions of patients with herpes zoster / 中华皮肤科杂志

Objective@#To observe changes in expression of autophagy proteins in peripheral CD4+ T lymphocytes and the epidermis of skin lesions, as well as generation of autophagy vesicles in epidermal cells in skin lesions of patients with herpes zoster, and to explore the relationship between varicella-herpes zoster virus (VZV) infection and autophagy.@*Methods@#Totally, 35 patients with herpes zoster were enrolled from Department of Dermatology, General Hospital of Southern Theater Command of PLA between December 2017 and December 2018, including 20 males and 15 females. Their age ranged from 18 to 79 (59.23 ± 9.27) years, pain duration was 5.14 ± 2.28 days, and lesion duration (from the onset of the lesion to the clinic visit) was 3.45 ± 1.77 days. Flow cytometry was performed to determine the expression of autophagy proteins including microtubule-associated protein 1 light chain 3B (LC3B) , Beclin-1 and p62 in peripheral blood CD4+ T lymphocytes of these patients. Thirty healthy adults served as control group. Lesional skin tissues were obtained from 12 patients with herpes zoster, and perilesional normal skin tissues of the same patient served as the control. Immunohistochemical study was conducted to determine the expression of autophagy proteins LC3B, Beclin-1 and p62 in epidermal tissues, and transmission electron microscopy to observe the generation of autophagy vesicles in epidermal cells. Two independent-sample t-test was carried out for intergroup comparison.@*Results@#The expression rates of autophagy proteins LC3B and Beclin-1 in peripheral CD4+ T lymphocytes were significantly higher in the herpes zoster group (61.23% ± 7.61%, 35.84% ± 4.22%, respectively) than in the control group (36.56% ± 4.27%, 15.34% ± 1.89%, respectively; t = 15.75, 24.56 respectively, both P < 0.01) , while the expression rate of p62 (5.75% ± 0.67%) was significantly lower in the herpes zoster group than in the control group (10.03% ± 1.15%, t = 18.65, P < 0.01) . Among the 12 patients with herpes zoster, the expression levels of LC3B and Beclin-1 in the epidermis were significantly higher in the skin lesions than in the perilesional normal skin tissues (t = 2.86, 4.58, P < 0.05) , but the expression level of p62 was significantly lower in the skin lesions than in the perilesional normal skin tissues (t = 2.43, P < 0.05) . Transmission electron microscopy showed formation of autophagy vesicles containing virus particles in epidermal cells in the skin lesions of 12 patients with herpes zoster, and vesicle counts were significantly higher in the skin lesions than in perilesional normal skin tissues (t = 9.67, P < 0.01) .@*Conclusion@#The autophagy level was elevated in peripheral CD4+ T lymphocytes and epidermis of skin lesions of patients with herpes zoster.

Detection of autophagy in peripheral CD4+ T lymphocytes and skin lesions of patients with herpes zoster / 中华皮肤科杂志

Objective To observe changes in expression of autophagy proteins in peripheral CD4+ T lymphocytes and the epidermis of skin lesions,as well as generation of autophagy vesicles in epidermal cells in skin lesions of patients with herpes zoster,and to explore the relationship between varicella-herpes zoster virus (VZV) infection and autophagy.Methods Totally,35 patients with herpes zoster were enrolled from Department of Dermatology,General Hospital of Southern Theater Command of PLA between December 2017 and December 2018,including 20 males and 15 females.Their age ranged from 18 to 79 (59.23 ± 9.27) years,pain duration was 5.14 ± 2.28 days,and lesion duration (from the onset of the lesion to the clinic visit) was 3.45 ± 1.77 days.Flow cytometry was performed to determine the expression of autophagy proteins including microtubule-associated protein 1 light chain 3B (LC3B),Beclin-1 and p62 in peripheral blood CD4 + T lymphocytes of these patients.Thirty healthy adults served as control group.Lesional skin tissues were obtained from 12 patients with herpes zoster,and perilesional normal skin tissues of the same patient served as the control.Immunohistochemical study was conducted to determine the expression of autophagy proteins LC3B,Beclin-1 and p62 in epidermal tissues,and transmission electron microscopy to observe the generation of autophagy vesicles in epidermal cells.Two independent-sample t-test was carried out for intergroup comparison.Results The expression rates of autophagy proteins LC3B and Beclin-1 in peripheral CD4 + T lymphocytes were significantly higher in the herpes zoster group (61.23％ ± 7.61％,35.84％ ± 4.22％,respectively) than in the control group (36.56％ ± 4.27％,15.34％ ± 1.89％,respectively;t =15.75,24.56 respectively,both P ＜ 0.01),while the expression rate of p62 (5.75％ ± 0.67％) was significantly lower in the herpes zoster group than in the control group (10.03％ ± 1.15％,t =18.65,P ＜ 0.01).Among the 12 patients with herpes zoster,the expression levels of LC3B and Beclin-1 in the epidermis were significantly higher in the skin lesions than in the perilesional normal skin tissues (t =2.86,4.58,P ＜ 0.05),but the expression level of p62 was significantly lower in the skin lesions than in the perilesional normal skin tissues (t =2.43,P ＜ 0.05).Transmission electron microscopy showed formation of autophagy vesicles containing virus particles in epidermal cells in the skin lesions of 12 patients with herpes zoster,and vesicle counts were significantly higher in the skin lesions than in perilesional normal skin tissues (t =9.67,P ＜ 0.01).Conclusion The autophagy level was elevated in peripheral CD4+ T lymphocytes and epidermis of skin lesions of patients with herpes zoster.

Variability in innate host immune responses to cryptococcosis

Cryptococcosis is an invasive fungal disease caused by Cryptococcus neoformans and the closely related species C. gattii. The severe form of the disease, cryptococcal meningitis (CM), is rapidly fatal without treatment. Although typically a disease of immunocompromised (especially HIV-positive) individuals, there is growing awareness of cryptococcal disease amongst non-immunocompromised patients. Whilst substantial progress has been made in understanding the pathogenicity of C. neoformans in HIV patients, prospective data on cryptococcosis outside the context of HIV remains lacking. Below we review how innate immune responses vary between hosts depending on immunological status, and discuss risk factors and predictors of disease outcome in different groups.

Saprolegnia parasitica Isolated from Rainbow Trout in Korea: Characterization, Anti-Saprolegnia Activity and Host Pathogen Interaction in Zebrafish Disease Model

Saprolegniasis is one of the most devastating oomycete diseases in freshwater fish which is caused by species in the genus Saprolegnia including Saprolegnia parasitica. In this study, we isolated the strain of S. parasitica from diseased rainbow trout in Korea. Morphological and molecular based identification confirmed that isolated oomycete belongs to the member of S. parasitica, supported by its typical features including cotton-like mycelium, zoospores and phylogenetic analysis with internal transcribed spacer region. Pathogenicity of isolated S. parasitica was developed in embryo, juvenile, and adult zebrafish as a disease model. Host-pathogen interaction in adult zebrafish was investigated at transcriptional level. Upon infection with S. parasitica, pathogen/antigen recognition and signaling (TLR2, TLR4b, TLR5b, NOD1, and major histocompatibility complex class I), pro/anti-inflammatory cytokines (interleukin [IL]-1β, tumor necrosis factor α, IL-6, IL-8, interferon γ, IL-12, and IL-10), matrix metalloproteinase (MMP9 and MMP13), cell surface molecules (CD8⁺ and CD4⁺) and antioxidant enzymes (superoxide dismutase, catalase) related genes were differentially modulated at 3- and 12-hr post infection. As an anti-Saprolegnia agent, plant based lawsone was applied to investigate on the susceptibility of S. parasitica showing the minimum inhibitory concentration and percentage inhibition of radial growth as 200 μg/mL and 31.8%, respectively. Moreover, natural lawsone changed the membrane permeability of S. parasitica mycelium and caused irreversible damage and disintegration to the cellular membranes of S. parasitica. Transcriptional responses of the genes of S. parasitica mycelium exposed to lawsone were altered, indicating that lawsone could be a potential anti-S. parasitica agent for controlling S. parasitica infection.

Disseminated cryptococcosis manifested as a single tumor in an immunocompetent patient, similar to the cutaneous primary forms

Abstract Cryptococcosis is a fungal infection caused by Cryptococcus neoformans that tends to affect immunocompromised individuals. The fungi are mostly acquired by inhalation, which leads to an initial pulmonary infection. Later, other organs - such as the central nervous system and the skin - can be affected by hematogenous spread. In addition, cutaneous contamination can occur by primary inoculation after injuries (primary cutaneous cryptococcosis), whose diagnosis is defined based on the absence of systemic involvement. The clinical presentation of cutaneous forms typically vary according to the infection mode. We report an unusual case of disseminated cryptococcosis in an immunocompetent patient with cutaneous lesions similar to those caused by primary inoculation. This clinical picture leads us to question the definition of primary cutaneous cryptococcosis established in the literature.

Different Extracts of Zingiber officinale Decrease Enterococcus faecalis Infection in Galleria mellonella

Dried, fresh and glycolic extracts of Zingiber officinale were obtained to evaluate the action against G. mellonella survival assay against Enterococcus faecalis infection. Eighty larvae were divided into: 1) E. faecalis suspension (control); 2) E. faecalis + fresh extract of Z. officinale (FEO); 3) E. faecalis + dried extract of Z. officinale (DEO); 4) E. faecalis + glycolic extract of Z. officinale (GEO); 5) Phosphate buffered saline (PBS). For control group, a 5 μL inoculum of standardized suspension (107 cells/mL) of E. faecalis (ATCC 29212) was injected into the last left proleg of each larva. For the treatment groups, after E. faecalis inoculation, the extracts were also injected, but into the last right proleg. The larvae were stored at 37 °C and the number of dead larvae was recorded daily for 168 h (7 days) to analyze the survival curve. The larvae were considered dead when they did not show any movement after touching. E. faecalis infection led to the death of 85% of the larvae after 168 h. Notwithstanding, in treatment groups with association of extracts, there was an increase in the survival rates of 50% (GEO), 61% (FEO) and 66% (DEO) of the larvae. In all treatment groups, the larvae exhibited a survival increase with statistically significant difference in relation to control group (p=0.0029). There were no statistically significant differences among treatment groups with different extracts (p=0.3859). It may be concluded that the tested extracts showed antimicrobial activity against E. faecalis infection by increasing the survival of Galleria mellonella larvae.

Extratos seco, fresco e glicólico de Zingiber officinale foram obtidos para avaliar suas ações por meio de ensaio de sobrevivência em G. mellonella contra infecção por Enterococcus faecalis. Oitenta larvas foram divididas em: 1) Suspensão de E. faecalis (controle); 2) E. faecalis + extrato fresco de Z. officinale (FEO); 3) E. faecalis + extrato seco de Z. officinale (DEO); 4) E. faecalis + extrato glicólico de Z. officinale (GEO); 5) Solução tampão fosfato salina (PBS). Para o grupo de controle, 5 µL de inóculo de suspensão padronizada (107 células/mL) de E. faecalis (ATCC 29212) foi injetado na última proleg esquerda de cada lagarta. Para os grupos com tratamento, após a injeção de E. faecalis, os extratos foram injetados na última proleg direita. Após as injeções, as lagartas foram armazenadas a 37 °C e o número de animais mortos foi registrado diariamente em 168 h (7 dias) para analisar a curva de sobrevivência. As lagartas foram consideradas mortas quando elas não mostraram qualquer movimento após o toque. A infecção por E. faecalis levou à morte de 85% das lagartas após 168 h. Não obstante, nos grupos de tratamento com associação dos extratos, houve um aumento nas taxas de sobrevivência de 50% (GEO), 61% (FEO) e 66% (DEO) das lagartas. Em todos os grupos com tratamento, as lagartas apresentaram um aumento na sobrevivência, com diferença estatisticamente significativa em relação ao grupo controle (p=0,0029). Não houve diferença estatisticamente significativa entre os tratamentos com os diferentes extratos (p=0,3859). Pode concluir-se que os extratos testados mostraram atividade antimicrobiana contra a infecção por E. faecalis, aumentando a sobrevivência das lagartas de G. mellonella.

Comparación de las características sociodemográficas, clínicas y microbiológicas de pacientes con periodontitis agresiva y crónica / Comparison of sociodemographic, clinical and microbiological characteristics of patients with aggressive and chronic periodontitis

Fundamento: algunos autores documentan diferencias en las características clínicas y en la prevalencia de los periodontopatógenos asociados con periodontitis agresiva y crónica en las poblaciones estudiadas. Objetivo: comparar las características sociodemográficas, clínicas y microbiológicas de pacientes con diagnóstico de periodontitis agresiva y periodontitis crónica en una población Colombiana. Métodos: en el presente estudio de corte transversal, el universo estuvo constituido por 94 pacientes: 40 con periodontitis crónica, 40 con periodontitis agresiva, y 14 controles sin periodontitis. Se realizó un examen periodontal completo que evaluó los parámetros periodontales más importantes. Se tomaron muestras microbiológicas de los pacientes en sitios con una profundidad de sondaje ≥ 5 mm. Resultados: se encontró una mayor proporción de Porphyromonas gingivalis y Tanerella forsythia en el grupo de periodontitis crónica (p<0.05). De la misma manera, se observó mayor proporción de Aggregatibacter actynomicetemcomitans en el grupo de periodontitis agresiva, con diferencias estadísticamente significativas (p<0.05). Se halló un mayor número de fumadores en el grupo de periodontitis crónica (p<0.05). La asociación entre A. actinomycetemcomitans y periodontitis agresiva arrojada por el análisis de regresión logística multinomial se conservó después de ajustar por variables de confusión. Se observaron peores parámetros periodontales en los pacientes con periodontitis crónica comparado con los otros dos grupos y las diferencias fueron estadísticamente significativas (p<0.05). Igualmente los pacientes con periodontitis agresiva presentaron mayor profundidad al sondaje y pérdida de inserción comparado con el grupo sin periodontitis (p<0.05). Conclusiones: los resultados del presente estudio muestran algunas particularidades microbiológicas y clínicas de la periodontitis agresiva y la periodontitis crónica en la población estudiada. En términos de estrategias de prevención y tratamiento de las enfermedades periodontales, los clínicos deben tener presente las potenciales diferencias en la microbiota subgingival y su asociación con el estado periodontal en una población particular.

Background: some authors documented difference in the clinical characteristics and in the prevalence of periodontopathogens associated with aggressive and chronic periodontitis among the populations studied. Objective: to compare the demographic, clinical and microbiological characteristics between patients diagnosed with aggressive periodontitis and chronic periodontitis in a Colombian population. Methods: in this cross-sectional study, the universe consisted of 94 patients: 40 with chronic periodontitis, 40 with aggressive periodontitis and 14 controls without periodontitis. A complete periodontal examination that evaluated the most important periodontal parameters was performed. Microbiological samples were taken from patients at sites with a probing depht ≥ 5 mm. Periodontopathogens were identified performing a polymerase chain reaction. The sociodemographic characteristics were assessed using a structured questionnaire. Results: a higher proportion of Porphyromonas gingivalis and Tanerella forsythia in chronic periodontitis group was found (p <0.05). Similarly, a higher proportion of Aggregatibacter actynomicetemcomitans was observed in the group of aggressive periodontitis, with statistically significant differences (p <0.05). A higher number of smokers in the chronic periodontitis group were found (p <0.05). The association between periodontitis and Aggregatibacter actinomycetemcomitans performed by the multinomial logistic regression analysis was retained after adjusting for confounding variables. Periodontal worst parameters were observed in patients with chronic periodontitis compared with the other two groups, and the differences were statistically significant (p <0.05). Similarly, patients with aggressive periodontitis had higher probing depth and attachment loss compared with those without periodontitis (p <0.05). Younger people and lower socioeconomic status were observed in the aggressive periodontitis group (p <0.05). Conclusions: the results of this study show some special microbiological and clinical characteristics of aggressive and chronic periodontitis in the population studied. In terms of strategies for prevention and treatment of periodontal disease, clinicians should be aware of potential differences in the subgingival microbiota and their association with periodontal status in a particular population.

Metabolomics in the fight against malaria

Metabolomics uses high-resolution mass spectrometry to provide a chemical fingerprint of thousands of metabolites present in cells, tissues or body fluids. Such metabolic phenotyping has been successfully used to study various biologic processes and disease states. High-resolution metabolomics can shed new light on the intricacies of host-parasite interactions in each stage of the Plasmodium life cycle and the downstream ramifications on the host’s metabolism, pathogenesis and disease. Such data can become integrated with other large datasets generated using top-down systems biology approaches and be utilised by computational biologists to develop and enhance models of malaria pathogenesis relevant for identifying new drug targets or intervention strategies. Here, we focus on the promise of metabolomics to complement systems biology approaches in the quest for novel interventions in the fight against malaria. We introduce the Malaria Host-Pathogen Interaction Center (MaHPIC), a new systems biology research coalition. A primary goal of the MaHPIC is to generate systems biology datasets relating to human and non-human primate (NHP) malaria parasites and their hosts making these openly available from an online relational database. Metabolomic data from NHP infections and clinical malaria infections from around the world will comprise a unique global resource.

Host immune responses to mycobacterial antigens and their implications for the development of a vaccine to control tuberculosis

Tuberculosis (TB) remains a worldwide health problem, causing around 2 million deaths per year. Despite the bacillus Calmette Guerin vaccine being available for more than 80 years, it has limited effectiveness in preventing TB, with inconsistent results in trials. This highlights the urgent need to develop an improved TB vaccine, based on a better understanding of host-pathogen interactions and immune responses during mycobacterial infection. Recent studies have revealed a potential role for autophagy, an intracellular homeostatic process, in vaccine development against TB, through enhanced immune activation. This review attempts to understand the host innate immune responses induced by a variety of protein antigens from Mycobacterium tuberculosis, and to identify future vaccine candidates against TB. We focus on recent advances in vaccine development strategies, through identification of new TB antigens using a variety of innovative tools. A new understanding of the host-pathogen relationship, and the usefulness of mycobacterial antigens as novel vaccine candidates, will contribute to the design of the next generation of vaccines, and to improving the host protective immune responses while limiting immunopathology during M. tuberculosis infection.

Stress response of Candida albicans to human hosts / 第二军医大学学报

Candida albicans (C. albicans'), one of the most commonly-seen opportunistic fungal pathogen, has drawn great public health concern in recent years. C. albicans faces numerous challenges when entering human hosts, including temperature, pH, osmotic stress and oxidative damage. How to adapt to these challenges is critical to the survival and infection ability of C. albicans. This article summarizes the stress response pathways of C. albicans to human host, and it is suggested that studying the stress response pathways may help to find newantifungal targets for C. albicans.

Innate immune response to oral bacteria and the immune evasive characteristics of periodontal pathogens

Periodontitis is a chronic inflammation of periodontal tissue caused by subgingival plaque-associated bacteria. Periodontitis has long been understood to be the result of an excessive host response to plaque bacteria. In addition, periodontal pathogens have been regarded as the causative agents that induce a hyperinflammatory response from the host. In this brief review, host-microbe interaction of nonperiodontopathic versus periodontopathic bacteria with innate immune components encountered in the gingival sulcus will be described. In particular, we will describe the susceptibility of these microbes to antimicrobial peptides (AMPs) and phagocytosis by neutrophils, the induction of tissue-destructive mediators from neutrophils, the induction of AMPs and interleukin (IL)-8 from gingival epithelial cells, and the pattern recognition receptors that mediate the regulation of AMPs and IL-8 in gingival epithelial cells. This review indicates that true periodontal pathogens are poor activators/suppressors of a host immune response, and they evade host defense mechanisms.

Dermatófitos: interação patógeno-hospedeiro e resistência a antifúngicos / Dermatophytes: host-pathogen interaction and antifungal resistance

As micoses cutâneas estão entre as infecções mais comuns em humanos e se tornaram um importante problema de saúde pública, principalmente por causarem infecções invasivas em pacientes imunodeprimidos. Durante a infecção, a interação dermatófito-hospedeiro desencadeia adaptações metabólicas específicas que permitem aos patógenos aderirem e penetrarem no tecido, remodelando seu metabolismo para captar nutrientes e superar os mecanismos de defesa do hospedeiro. Esse remodelamento metabólico e a inter-relação entre metabolismo, morfogênese e resposta ao estresse são importantes fatores que estão sendo intensamente avaliados em diversos patógenos. As células do hospedeiro também respondem aos estímulos do patógeno, ativando vias de sinalização intracelular que culminam no desencadeamento de uma resposta imune contra o agente infeccioso. O entendimento molecular dessas respostas metabólicas pode ajudar no estabelecimento de novas estratégias terapêuticas. Nesta revisão, são abordados diferentes aspectos da biologia dos dermatófitos, com ênfase na interação dermatófito-hospedeiro e nos mecanismos de resistência a antifúngicos.

Cutaneous mycoses are among the most common infections in humans and have become an important public health issue because they cause invasive infections in immunocompromised patients. During the infectious process, dermatophyte-host interactions trigger specific metabolic adaptations that allow the pathogen to adhere to and penetrate the host tissue, scavenge nutrients, and overcome the host defense mechanisms. This metabolic shift and the interplay between metabolism, morphogenesis and stress response are important factors that have been extensively studied in several pathogens. Host cells also respond to the pathogen stimuli by activating intracellular signaling pathways that trigger the immune response against the infectious agent. The comprehension of the molecular aspects of these responses may help to establish new therapeutical strategies. In this review, different aspects of the biology of dermatophytes are addressed, with emphasis on the dermatophyte-host interaction and the mechanisms of antifungal resistance.

Role of swine as host and a mixing vessel in evolution of 2009 novel influenza virus A/H1N1 / 第二军医大学学报

Several epidemic influenza viruses leading to worldwide periodical pandemics all result from the genetic reassortment of different influenza viruses. The novel 2009 A/H1N1 virus is a reassortment virus evolved from swine influenza virus A/H1N1, avian influenza virus H5N1, and human influenza virus A/H1N1. The 8 fragmente genes of the novel A/H1N1 virus had their own evolutionary characteristics. All the pandemic viruses in humans originate from avian influenza viruses and are transferred into humans after reassortment processes in pigs. Pigs as middle host and a mixing vessel of influenza A virus play an important role in the evolution of the 2009 novel A/H1N1 virus. More attention should be paid on the role of swine in the prevention and control of novel H1N1 virus epidemics in future.

Comparative study of synonymous codon usage variations between the nucleocapsid and spike genes of coronavirus, and C-type lectin domain genes of human and mouse

Coronaviruses (CoVs) are single-stranded RNA viruses which contain the largest RNA genomes, and severe acute respiratory syndrome coronavirus (SARS-CoV), a newly found group 2 CoV, emerged as infectious disease with high mortality rate. In this study, we compared the synonymous codon usage patterns between the nucleocapsid and spike genes of CoVs, and C-type lectin domain (CTLD) genes of human and mouse on the codon basis. Findings indicate that the nucleocapsid genes of CoVs were affected from the synonymous codon usage bias than spike genes, and the CTLDs of human and mouse partially overlapped with the nucleocapsid genes of CoVs. In addition, we observed that CTLDs which showed the similar relative synonymous codon usage (RSCU) patterns with CoVs were commonly derived from the human chromosome 12, and mouse chromosome 6 and 12, suggesting that there might be a specific genomic region or chromosomes which show a more similar synonymous codon usage pattern with viral genes. Our findings contribute to developing the codon-optimization method in DNA vaccines, and further study is needed to determine a specific correlation between the codon usage patterns and the chromosomal locations in higher organisms.

Role of swine as host and a mixing vessel in evolution of 2009 novel influenza virus A/H1N1 / 第二军医大学学报

Several epidemic influenza viruses leading to worldwide periodical pandemics all result from the genetic reassortment of different influenza viruses.The novel 2009 A/H1N1 virus is a reassortment virus evolved from swine influenza virus A/H1N1,avian influenza virus H5N1,and human influenza virus A/H1N1.The 8 fragmente genes of the novel A/H1N1 virus had their own evolutionary characteristics.All the pandemic viruses in humans originate from avian influenza viruses and are transferred into humans after reassortment processes in pigs.Pigs as middle host and a mixing vessel of influenza A virus play an important role in the evolution of the 2009 novel A/H1N1 virus.More attention should be paid on the role of swine in the prevention and control of novel H1N1 virus epidemics in future.