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.
Animals ; Medicine, Chinese Traditional ; Communicable Diseases/drug therapy* ; Mathematics ; Host-Pathogen Interactions ; Drugs, Chinese Herbal/therapeutic use*

Helminth infections are widespread worldwide, and pose a serious threat to human health and animal husbandry development. Understanding of helminth-host interactions is critical to effective control and ultimate eradication of helminthiasis. Following host infections, helminth infections firstly initiate innate immune responses and then mediate adaptive immune responses. Type 1 immune responses are predominant at early stage of helminth infections, which mainly play anti-infective actions, and type 2 immune responses are predominant at late stage of infections, which are associated with helminth immune evasion and aggravation of tissue damages. This review summarizes the progress of researches on type 1/2 immune responses-associated signaling pathways mediated by helminth infections in hosts.
Animals ; Humans ; Helminthiasis ; Helminths ; Immunity, Innate ; Signal Transduction ; Host-Parasite Interactions

Autophagy is an intracellular degradation process that maintains cellular homeostasis. It is essential for protecting organisms from environmental stress. Autophagy can help the host to eliminate invading pathogens, including bacteria, viruses, fungi, and parasites. However, pathogens have evolved multiple strategies to interfere with autophagic signaling pathways or inhibit the fusion of autophagosomes with lysosomes to form autolysosomes. Moreover, host cell matrix degradation by different types of autophagy can be used for the proliferation and reproduction of pathogens. Thus, determining the roles and mechanisms of autophagy during pathogen infections will promote understanding of the mechanisms of pathogen‍‒‍host interactions and provide new strategies for the treatment of infectious diseases.
Autophagy ; Bacteria ; Host-Pathogen Interactions ; Lysosomes ; Signal Transduction

Head and neck squamous cell carcinoma (HNSCC), an aggressive malignancy, is characterized by high morbidity and low survival rates with limited therapeutic options outside of regional surgery, conventional cytotoxic chemotherapy, and irradiation. Increasing studies have supported the synergistic role of the tumor microenvironment (TME) in cancer advancement. The immune system, in particular, plays a key role in surveillance against the initiation, development, and progression of HNSCC. The understanding of how neoplastic cells evolve and evade the immune system whether through self-immunogenicity manipulation, or expression of immunosuppressive mediators, provides the foundation for the development of advanced therapies. Furthermore, the crosstalk between cancer cells and the host immune system have a detrimental effect on the TME promoting angiogenesis, proliferation, and metastasis. This review provides a recent insight into the role of the key inflammatory cells infiltrating the TME, with a focus on reviewing immunological principles related to HNSCC, as cancer immunosurveillance and immune escape, including a brief overview of current immunotherapeutic strategies and ongoing clinical trials.
Head and Neck Neoplasms/therapy* ; Humans ; Immune Evasion ; Squamous Cell Carcinoma of Head and Neck ; Tumor Microenvironment

Aims: Expression of recombinant proteins across a range of different host organisms has profound contribution to the advancement in biotechnology. In this study, we aimed to construct a highly versatile broad host range (BHR) expression vector, designated as pYL101C. Methodology and results: The Golden Gate cloning approach was used to construct pYL101C. Key features of pYL101C include a strong integron promoter (PINTc), a BHR pBBR1 origin of replication (ori), gentamycin resistance gene (GmR) as a selectable marker and a multiple cloning site (MCS) downstream of the promoter for easy-cloning purpose. To verify the functionality of pYL101C, we cloned the superfolder green fluorescent protein (sfGFP) reporter gene into pYL101C and transferred the resultant recombinant plasmid pYL101C::sfGFP into various Gram-negative bacteria. Transformants obtained stably expressed strong green fluorescence under blue light excitation even without selection after four passages. Conclusion, significance and impact of study The constructed BHR expression vector, pYL101C and recombinant pYL101C::sfGFP are stable and can be used to monitor the presence of Gram-negative bacteria, such as endophytes and pathogens in their hosts and environment.
Host Specificity ; Plasmids ; Cloning, Molecular

Aims: Antimicrobial compounds are bioactive compounds that have ability to inhibit microbial growth activities. This study aimed to screen and identify bacteria associated with Haliclona sp. sponges from Enggano Island, Indonesia that had potential to produce antimicrobial compounds against Escherichia coli, Candida albicans and Staphylococcus epidermidis. Methodology and results: The method used to screen and identify bacteria in this study including screening assay, morphological identification, Gram staining and spore staining method, biochemical tests and molecular identification based on 16S rRNA gene. This study resulted 16 isolates which were successfully isolated from Haliclona sp. According to screening assay, 5 isolates could potentially produce antimicrobial compounds coded as HEBS1, HEBS3, HEBS6, HEBB2 and HEBB3. Based on Gram staining, spore staining, biochemical test and molecular identification results, HEBS1 had proximity to Brachybacterium paraconglomeratum, HEBS3 had proximity to Kocuria palustris, HEBS6 had proximity to Psychrobacter pasificensis, HEBB2 had proximity to Bacillus aryabhattai, and HEBB3 had proximity to Bacillus toyonensis. Conclusion, significance and impact of study From 16 isolates that successfully isolated, there were 5 isolates that could potentially produce antimicrobial compounds against Escherichia coli, Staphylococcus epidermidis and Candida albicans. These isolates can be served as antimicrobial compounds producer. However, identification and purification of these antimicrobial compounds are needed to be done before applied it for medicine in the future.
Haliclona--microbiology ; Host-Pathogen Interactions

Since December 2019, the novel coronavirus (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has spread to many countries around the world, developing into a global pandemic with increasing numbers of deaths reported worldwide. To data, although some vaccines have been developed, there are no ideal drugs to treat novel coronavirus pneumonia (coronavirus disease 2019 (COVID-19)). By examining the structure of the coronavirus and briefly describing its possible pathogenesis based on recent autopsy reports conducted by various teams worldwide, this review analyzes the possible structural and functional changes of the human body upon infection with SARS-CoV-2. We observed that the most prominent pathological changes in COVID-19 patients are diffuse alveolar damage (DAD) of the lungs and microthrombus formation, resulting in an imbalance of the ventilation/perfusion ratio and respiratory failure. Although direct evidence of viral infection can also be found in other organs and tissues, the viral load is relatively small. The conclusion that the injuries of the extra-pulmonary organs are directly caused by the virus needs further investigation.
COVID-19/physiopathology* ; Human Body ; Humans ; Immune Evasion ; Lung/virology* ; Viral Load

OBJECTIVE: To investigate the mechanisms of anti-apoptosis and immune evasion in drug-resistant leukemia cells mediated by STAT3, further to explore the possible mechanism of leukemia relapse caused by minimal residual. METHODS: Drug-resistance leukemia cell line was established by transfecting pcDNA3.1-STAT3 into K562 cells (K562/STAT3). The expression of STAT3, BAX and NKG2D ligands (MICA and ULBP1) in K562/-cells, K562/STAT3 were detected by Western blot and/or RQ-PCR. Cells apoptosis and the killing effect of NK cells on leukemia cells were detected by flow cytometry. RESULTS: The expression of the total STAT3, STAT3 phosphorylation in K562/STAT3 was significantly increased, and P-gp mRNA expression was increased also significantly (P<0.005). In K562/STAT3 cells, the expression of pro-apoptotic BAX (P=0.005) was significantly lower, and the number of apoptotic cells (P=0.002) induced by adriamycin was significantly decreased as compared with those in K562/- cells. After K562/STAT3 cells were treated by STAT3 inhibitor (SH-4-54), the expression of BAX mRNA (P=0.017) was significantly higher and the number of apoptotic cells (P=0.005) was significantly increased. The MICA and ULBP1 mRNA expression in K562/STAT3 cells was significantly lower than that in K562/- cells, and also for MICA and ULBP1 protein (MICA and ULPB1 mRNA: P<0.0001, MICA protein: P=0.001, ULPB1 protein: P=0.022). After K562/STAT3 cells were treated with STAT3 inhibitor (SH-4-54), the expression of MICA mRNA and protein was increased (mRNA: P=0.001, protein: P=0.002), but ULBP1 mRNA and protein showed no significantly change (mRNA: P=0.137, protein: P=0.1905). The cytotoxicity of NK cells to K562/STAT3 cells was susceptible as compared with K562/- (P=0.002), but the cytotoxicity of K562/STAT3 cells to NK cell could be recovered by STAT3 inhibitor (P=0.006). CONCLUSION STAT3 phosphorylation can inhibits cell apoptosis and promotes cell immune escape. STAT3 inhibitors can promote the apoptosis of leukemia cells and increase their sensitivity to NK cells.
Apoptosis ; Humans ; Immune Evasion ; K562 Cells ; Killer Cells, Natural ; Leukemia ; Pharmaceutical Preparations ; STAT3 Transcription Factor

Adaptation, Physiological ; Adenosine Monophosphate ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Administration, Intranasal ; Alanine ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Animals ; Betacoronavirus ; genetics ; physiology ; Chlorocebus aethiops ; Coronavirus Infections ; drug therapy ; virology ; Disease Models, Animal ; Female ; Host Specificity ; genetics ; Lung ; pathology ; virology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mutation, Missense ; Nasal Mucosa ; virology ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; RNA, Viral ; administration & dosage ; genetics ; Turbinates ; virology ; Vero Cells ; Viral Load ; Virus Replication

BACKGROUND: Nanoparticle-mediated photothermal therapy (PTT) has been well studied as a treatment for cancer. However, the therapeutic outcome of PTT is often hindered by the penetration depth of laser light. In the tumor margin beyond the laser penetration limit, tumor recurrence often occurs, bypassing the immune response of the host. Accumulating evidence suggests the prominent role of tumor microenvironment (TME) and its interactions with the immune components contribute to an immunosuppressive milieu during the post-therapy period. Here, we explored the immunosuppressive cascade generated after PTT, which is responsible for tumor recurrence, and identified the potential targets to achieve an effective PTT period. METHODS: Here, we investigated the immunosuppressive cascade generated after PTT in a CT26 tumor bearing mouse. The liposomal system loaded with the indocyanine green (ICG) was utilized for the generation of PTT with high efficiency. Immunological factors such as cytokines and protein expressions post-therapy were investigated through enzyme-linked immunosorbent assay, flow cytometry and western blot analysis. RESULTS: Our results suggested that PTT with ICG-loaded liposomes (Lipo-ICG) was effective for the first 5 days after treatment, resulting in tumor suppression. However, an immunosuppressive and pro-inflammatory environment developed thereafter, causing the recruitment and upregulation of the immune evasion factors of heat shock protein 70, programmed death ligand 1, indoleamine-dioxygenase, interleukin-6, transforming growth factor-β, regulatory T-cells, and myeloid-derived suppressor cells, to develop immunotolerance. CONCLUSION: Collectively, these findings have determined potential therapeutic targets to modulate the TME during PTT and achieve tumor ablation without remission.
Animals ; Blotting, Western ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; HSP70 Heat-Shock Proteins ; Immune Evasion ; Immunologic Factors ; Immunosuppression ; Indocyanine Green ; Interleukin-6 ; Liposomes ; Mice ; Recurrence ; T-Lymphocytes, Regulatory ; Tumor Microenvironment ; Up-Regulation