Pharmacological Investigation on the Qi-Invigorating Action of Schisandrin B: Effects on Mitochondrial ATP Generation in Multiple Tissues and Innate/Adaptive Immunity in Mice

Schisandrae Fructus, containing schisandrin B (Sch B) as its main active component, is recognized in traditional Chinese medicine (TCM) for its Qi-invigorating properties in the five visceral organs. Our laboratory has shown that the Qi-invigorating action of Chinese tonifying herbs is linked to increased mitochondrial ATP generation and an enhancement in mitochondrial glutathione redox status. To explore whether Sch B can exert Qi-invigorating actions across various tissues, we investigated the effects of Sch B treatment on mitochondrial ATP generation and glutathione redox status in multiple mouse tissues ex vivo. In line with TCM theory, which posits that Zheng Qi generation relies on the Qi function of the visceral organs, we also examined Sch B’s impact on natural killer cell activity and antigen-induced splenocyte proliferation, both serving as indirect measures of Zheng Qi. Our findings revealed that Sch B treatment consistently enhanced mitochondrial ATP generation and improved mitochondrial glutathione redox status in mouse tissues. This boost in mitochondrial function was associated with stimulated innate and adaptive immune responses, marked by increased natural killer cell activity and antigen-induced T/B cell proliferation, potentially through the increased generation of Zheng Qi.

Unveiling the dynamic role of innate and adaptive immune cells in COPD pathogenesis induced by cigarette smoke

Chronic obstructive pulmonary disease(COPD)is a multifaceted syndrome characterized by a dysregulated inflammatory cascade within the respiratory system,primarily triggered by exposure to harmful particles and gases,notably from cigarette smoke.This inflammatory response is orchestrated by innate immune cells like macrophages and epithelial cells,which recognize danger signals released from damaged cells.Prolonged inflammation prompts an adaptive immune reaction mediated by dendritic cells,culminating in the formation of lymphoid follicles and involving a complex interplay of T and B cells,as well as cytotoxic activity.Additionally,both viral and bacterial infections exacerbate COPD by further igniting inflammatory pathways,perpetuating the chronic inflammatory state.This comprehensive review encapsulates the intricate interplay between innate and adaptive immunity in COPD,with a particular focus on the role of cigarette smoke in its pathogenesis and potential therapeutic targets.

Differential Effects of Yin- and Yang-Chinese Tonifying Herbs on Innate and Adaptive Immunity

The present study investigated the effect of treatment with methanolic extracts of Yin- and Yang-Chinese tonifying herbs on concanavalin A (Con A)/lipopolysaccharide (LPS)-stimulated splenocyte proliferation (adaptive immunity) and natural killer (NK) cell activity (innate immunity) in an ex vivo mouse model. The results indicated that while treatment with most Yin herbal extracts potentiated the Con A/LPS-stimulated splenocyte proliferation, only Yang (but not Yin) herbal extracts stimulated NK cell activity. The differential effects of Yin- and Yang-Chinese tonifying herbs on innate and adaptive immunity are consistent with the Chinese medicine theory which depicts the Yin and Yang functional components of Zheng Qi (vital energy), with the Yang component being responsible for the first line of defense against invading microorganisms (i.e., innate immunity) and the Yin oner serving as a follow-up defensive response (adaptive immunity).

Harnessing immunity:Immunomodulatory therapies in COVID-19

An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators.

Intelligent direct analysis of physical and mechanical parameters of tunnel surrounding rock based on adaptive immunity algorithm and BP neural network

Because of complexity and non-predictability of the tunnel surrounding rock, the problem with the determination of the physical and mechanical parameters of the surrounding rock has become a main obstacle to theoretical research and numerical analysis in tunnel engineering. During design, it is a frequent practice, therefore, to give recommended values by analog based on experience. It is a key point in current research to make use of the displacement back analytic method to comparatively accurately determine the parameters of the surrounding rock whereas artificial intelligence possesses an exceptionally strong capability of identifying, expressing and coping with such complex non-linear relationships. The parameters can be verified by searching the optimal network structure, using back analysis on measured data to search optimal parameters and performing direct computation of the obtained results. In the current paper, the direct analysis is performed with the biological emulation system and the software of Fast Lagrangian Analysis of Continua (FLAC3D. The high non-linearity, network reasoning and coupling ability of the neural network are employed. The output vector required of the training of the neural network is obtained with the numerical analysis software. And the overall space search is conducted by employing the Adaptive Immunity Algorithm. As a result, we are able to avoid the shortcoming that multiple parameters and optimized parameters are easy to fall into a local extremum. At the same time, the computing speed and efficiency are increased as well. Further, in the paper satisfactory conclusions are arrived at through the intelligent direct-back analysis on the monitored and measured data at the Erdaoya tunneling project. The results show that the physical and mechanical parameters obtained by the intelligent direct-back analysis proposed in the current paper have effectively improved the recommended values in the original prospecting data. This is of practical significance to the appraisal of stability and informationization design of the surrounding rock.

Tetrahedral Framework Nucleic Acid-Based Delivery of Resveratrol Alleviates Insulin Resistance:From Innate to Adaptive Immunity

Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current therapeutic approaches lack efficacy and immunomodulatory capacity.Thus,a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance.Here,we synthesized a tetrahedral framework nucleic acid(tFNA)nanoparticle that carried resveratrol(RSV)to inhibit tissue inflammation and improve insulin sensitivity in obese mice.The prepared nanoparticles,namely tFNAs-RSV,possessed the characteristics of simple synthesis,stable properties,good water solubility,and superior biocompatibility.The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy.In high-fat diet(HFD)-fed mice,the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status.tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages.As for adaptive immunity,the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg,leading to the alleviation of insulin resistance.Furthermore,this study is the first to demonstrate that tFNAs,a nucleic acid material,possess immunomodulatory capacity.Collectively,our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice,suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.

Is there a role for adaptive immunity in nonalcoholic steatohepatitis?

The growing diffusion of nonalcoholic fatty liver disease(NAFLD) is a consequence of the worldwide increase in the prevalence of obesity.Oxidative stress is widely recognized to play a pivotal role in NAFLD evolution to nonalcoholic steatohepatitis(NASH).Here we review recent evidence suggesting that oxidative stress-derived antigens originating within fatty livers stimulate both humoral and cellular adaptive immune responses and the possible mechanisms involved in sustaining hepatic inflammation in NASH.

Long-Term Treatment with a Compound Polysaccharide-Based Health Product (Infinitus Polysac Plus) Enhances Innate and Adaptive Immunity in Mice

This study aimed to investigate the effects of a compound polysaccharide-based health product (Infinitus Polysac Plus, IPP) on innate and adaptive immunity in mice. Both ex vivo/in vivo mouse models and an in vitro system using cultured mouse splenocytes were adopted for the assessment of innate and adaptive immunity. For the innate immune response, long-term IPP treatment (0.26 and 0.78 g/kg * 20 doses) enhanced the carbon clearance activity and phagocytic rate of macrophages, as well as natural killer cell activity in mice. The IPP-induced increase in natural killer cell activity was accompanied by the suppression of tumor growth in Sarcoma-180 cell-inoculated mice. For the adaptive immune response, while long-term IPP treatment increased the splenocyte index in mice, IPP incubation with mouse splenocytes in vitro potentiated their concanavalin A-stimulated proliferation. Long-term IPP treatment significantly restored the hemolytic activity of serum on sheep red blood cells and dinitrofluorobenezene-induced delayed-type hypersensitivity in sensitized and immunosuppressed mice. In conclusion, the results indicate that long-term IPP treatment produces stimulatory effects on both innate and adaptive immunity in mice.

The prolactin-inducible-protein (PIP): A regulatory molecule in adaptive and innate immunity

The Prolactin-inducible-protein (PIP)/Gross Cystic Disease Fluid Protein-15 (GCDFP-15) gene is highly expressed in salivary, lacrimal and sweat glands and the protein abundantly found in the secretions that originate from these glands;saliva, tears and sweat. PIP is thus considered to be strategically located at sites viewed as the first port of entry for invading organisms. PIP is also found over-expressed under abnormal and pathological conditions of the breast and prostate. The function of PIP has yet to be defined but it has been implicated to play a role in immunity, with respect to bacterial and viral infection, cancer and fertility. Despite such predictive functions, there is still no clear demonstration of an immunoregulatory role for PIP. In this review we will focus on accumulating evidence that suggests a role for PIP in both innate and adaptive immunity. Moreover, we will discuss recent evidence that defines a modulatory role for PIP with regards to a CD4+ T cell immune response, identifying for the first time, a critical role for PIP in effective cell-mediated immunity against an intracellular pathogen.

Complement and its role in innate and adaptive immune responses

The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.

Inflammatory bowel disease requires the interplay between innate and adaptive immune signals

Inflammatory bowl disease （IBD） is a type 1 T helper cell （Th1）-mediated autoimmune disease. Various studies have revealed that environmental pathogens also play a significant role in the initiation and progression of this disease. Interestingly, the pathogenesis of IBD has been shown to be related to nitric oxide （NO） released from innate immune cells. Although NO is known to be highly toxic to the gut epithelia, there is very little information about the regulation of NO production, One major question in the etiology of IBD is how Thl cells and pathogens interact in the induction of IBD. In present study, we focused on the regulation of NO. We show that macrophages require both interferon-γ, （IFN-γ）-mediated and TLR4-mediated signals for the production of NO, which causes inflammation in the intestine and subsequently IBD. Thus, IBD is the result of concerted actions of innate immune signals, such as the binding of LPS to TLR-4, and adaptive immune signals, such as IFN-γ produced by Thl cells.

Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

Innate and adaptive immune escape mechanisms of hepatitis B virus

Chronic hepatitis B virus(HBV)infection is an international health problem with extremely high mortality and morbidity rates.Although current clinical chronic hepatitis B(CHB)treatment strategies can partly inhibit and eliminate HBV,viral breakthrough may result due to non-adherence to treatment,the emergence of viral resistance,and a long treatment cycle.Persistent CHB infection arises as a consequence of complex interactions between the virus and the host innate and adaptive immune systems.Therefore,understanding the immune escape mechanisms involved in persistent HBV infection is important for designing novel CHB treatment strategies to clear HBV and achieve long-lasting immune control.This review details the immunological and biological characteristics and escape mechanisms of HBV and the novel immune-based therapies that are currently used for treating HBV.

Role of toll-like receptor 4 in eliciting adaptive immune responses against recombinant BCG expressing the C-terminus of merozoite surface protein-1 of Plasmodium falciparum

Objective: To determine the role of toll-like receptor 4(TLR-4) in eliciting cellular and humoral immune responses against recombinant Mycobacterium bovis bacille Calmette-Guérin(rB CG) expressing the C-terminus of merozoite surface protein-1 of Plasmodium falciparum. Methods: Six groups of mice(n=6 per group) were injected with phosphate buffered saline T80, BCG or r BCG intraperitoneally, in the presence or absence of a TLR-4 inhibitor; TAK-242. Enzyme-linked immunosorbent assay was carried out for serum total IgG, IgG 1, Ig G2 a and Ig G2 b determination. Spleens were also harvested and splenocytes cultured for determination of intracellular cytokines; IL-4 and IFN-毭 via enzyme-linked immunosorbent assay. Results: The production of total Ig G, and the subclasses Ig G1, Ig G2 a and Ig G2 b was significantly higher in rB CG-immunised mice than BCG and phosphate buffered saline immunised mice in the absence of TAK-242. A significant rise in total IgG occurred with more booster immunisations. The level of IgG 2 a was highest, followed by IgG 2 b, then IgG 1. The production of both IL-4 and IFN-were inhibited in t毭 was also highest in the rB CG immunised groups. These significant riseshe presence of TAK-242. Conclusions: We present evidence of the role of TLR-4 in the increased production of total IgG, IgG 1, IgG 2 a and IgG 2 b, as well as IL-4 and IFN-毭 in response to our rB CG construct.

Genes of the adaptive immune system are expressed early in zebrafish larval development following lipopolysaccharide stimulation

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.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Adaptive Immune Evolutionary Algorithms Based on Immune Network Regulatory Mechanism

Based on immune network regulatory mechanism, a new adaptive immune evolutionary algorithm (AIEA) is proposed to improve the performance of genetic algorithms (GA) in this paper. AIEA adopts novel selection operation according to the stimulation level of each antibody. A memory base for good antibodies is devised simultaneously to raise the convergent rapidity of the algorithm and adaptive adjusting strategy of antibody population is used for preventing the loss of the population adversity. The experiments show AIEA has better convergence performance than standard genetic algorithm and is capable of maintaining the adversity of the population and solving function optimization problems in an efficient and reliable way.

Innate and adaptive immune responses against picornaviruses and their counteractions: An overview

Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate and adaptive, induced after infection, and the subsequent interactions of the viruses with the immune system. The defense mechanisms of the host and the countermeasures of the virus significantly contribute to the pathogenesis of the infections. Important human pathogens are poliovirus, coxsackievirus, human rhinovirus and hepatitis A virus. These viruses are the beststudied members of the family, and in this review we want to present the major aspects of the reciprocal effects between the immune system and these viruses.

A New Method for Fastening the Convergence of Immune Algorithms Using an Adaptive Mutation Approach

This paper presents a new adaptive mutation approach for fastening the convergence of immune algorithms (IAs). This method is adopted to realize the twin goals of maintaining diversity in the population and sustaining the convergence capacity of the IA. In this method, the mutation rate (pm) is adaptively varied depending on the fitness values of the solutions. Solutions of high fitness are protected, while solutions with sub-average fitness are totally disrupted. A solution to the problem of deciding the optimal value of pm is obtained. Experiments are carried out to compare the proposed approach to traditional one on a set of optimization problems. These are namely: 1) an exponential multi-variable function;2) a rapidly varying multimodal function and 3) design of a second order 2-D narrow band recursive LPF. Simulation results show that the proposed method efficiently improves IA’s performance and prevents it from getting stuck at a local optimum.

Adaptive template filter method for image processing based on immune genetic algorithm

To preserve the original signal as much as possible and filter random noises as many as possible in image processing,a threshold optimization-based adaptive template filtering algorithm was proposed.Unlike conventional filters whose template shapes and coefficients were fixed,multi-templates were defined and the right template for each pixel could be matched adaptively based on local image characteristics in the proposed method.The superiority of this method was verified by former results concerning the matching experiment of actual image with the comparison of conventional filtering methods.The adaptive search ability of immune genetic algorithm with the elitist selection and elitist crossover(IGAE) was used to optimize threshold t of the transformation function,and then combined with wavelet transformation to estimate noise variance.Multi-experiments were performed to test the validity of IGAE.The results show that the filtered result of t obtained by IGAE is superior to that of t obtained by other methods,IGAE has a faster convergence speed and a higher computational efficiency compared with the canonical genetic algorithm with the elitism and the immune algorithm with the information entropy and elitism by multi-experiments.