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Abstract To date, numerable reviews are found in the literature prominent to the effect of caffeine on the immune system, with the latest review published in 2006. Database screening reveals around three thousand articles that have been published during the last decade. Interestingly, less than hundred articles involved humans and rodents as tested models, out of which 20% is of interest to this paper excluding studies done on the nervous and cardiac systems, and in pregnant and cancer cases. In this review, information pertaining to the experimental setup of various studies, namely, the tested model, the study type (in vivo or in vitro), and caffeine dose is covered to discern the behaviour of major cellular and molecular immune components in light of caffeine exposure. Although it is hard to extrapolate results done in rodents to humans and to relay conclusions from in vitro to in vivo studies, most of the collected data favor the suppressive effects of caffeine on the proliferation of stimulated lymphocytes. Macrophages and natural killer cells also exhibited a reduced activity in the presence of high caffeine doses compared to increased activity at low doses. Immunosuppression is also supported by reduced levels of major anti-inflammatory cytokines, IL-2, IL-6, TNF-α. Moreover, certain innate and adaptive immune receptors, such as TLR1, TLR2, TLR4, and MHC class I-related chain B (MICB) molecules, exhibited decreased expression levels. Thus, we support the use of caffeine to alleviate various inflammatory conditions and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Honey is one of the most popular functional foods, speculated to be in use since the advent of human civilization. Its health-protective activity is endorsed by many religions and traditional medicines. In Unani medicine, honey is prescribed for many health conditions as wound-healing, anti-inflammatory, anti-diabetic, etc. In the present era, honey is gaining popularity over sugar for its myriad health benefits and low glycemic index. This review attempts to provide a comprehensive account of the biological activities and potential therapeutic uses of honey, with scientific evidence. In this paper, we have provided a comprehensive overview of historical uses, types, physical characteristics, bioactive constituents and pharmacological activities of honey. The information was gathered from Classical Unani textbooks and leading scientific databases. There is a plethora of information regarding various therapeutic activities of honey, and it is daunting to draw practical conclusions. Hence, in this paper, we have tried to summarize those aspects which are most relevant to clinical application. Many important bioactive constituents are identified in different honey types, e.g. phenolics, proteins, vitamins, carbohydrates, organic acids, etc., which exert important biological activities like anti-microbial, wound healing, immunomodulatory, anti-toxin, antioxidant, and many others. Honey has the potential to alleviate many lifestyle disorders, mitigate the adverse effects of drugs and toxins, and also provide healthy nutrition. Although conclusive clinical evidence is not available, yet honey may potentially be a safer alternative to sucrose for diabetic patients. [Display omitted] • Honey is one of the best-known functional foods, used since antiquity. • Nearly 300 different types of honey are known over the world. • Honey has a low glycemic index and contains several beneficial bioactive chemicals. • Most types of honey have antioxidant, antimicrobial, and many other health effects. • Honey is also speculated to be safer than sucrose for diabetic patients. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have revolutionized the current treatment landscape for cancer, yet the response rates of ICIs remain unmet. Synergistic with immunotherapy, low-dose radiotherapy (LDRT) has been demonstrated to activate anti-tumor immunity – a transition from traditional radiation therapy geared toward local radical treatment to a type of immunological adjuvant. As such, studies utilizing LDRT to enhance the efficacy of immunotherapy have been increasing preclinically and clinically. This paper reviews the recent strategies of using LDRT to overcome the resistance of ICIs, as well as providing potential opportunities in cancer treatment. Despite the potential of LDRT in immunotherapy is recognized, the mechanisms behind this form of treatment remain largely elusive. Thus, we reviewed history, mechanisms and challenges associated with this form of treatment, as well as different modes of its application, to provide relatively accurate practice standards for LDRT as a sensitizing treatment when combined with immunotherapy or radio-immunotherapy. [Display omitted] • We sheds new light on the history, mechanisms, as well as modes of application in LDRT. • We provided relatively accurate practice standards for LDRT as a sensitizing treatment. • We are trying to explore LDRT to overcome the resistance of ICIs. • We evaluated the potential and challenges associated with LDRT. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Atractylodes macrocephala Koidz. (called Baizhu in China) is a medicinal plant that has long been used as a tonic agent in various ethno-medical systems in East Asia, especially in China, for the treatment of gastrointestinal dysfunction, cancer, osteoporosis, obesity, and fetal irritability. Aim of the review This review aims to provide a systematic summary on the botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics, and toxicology of A. macrocephala to explore the future therapeutic potential and scientific potential of this plant. Materials and methods A literature search was performed on A. macrocephala using scientific databases including Web of Science, Google Scholar, Baidu Scholar, Springer, PubMed, SciFinder, and ScienceDirect. Information was also collected from classic books of Chinese herbal medicine, Ph.D. and M.Sc. dissertations, unpublished materials, and local conference papers on toxicology. Plant taxonomy was confirmed to the database “The Plant List” ( www.theplantlist.org ). Results More than 79 chemical compounds have been isolated from A. macrocephala , including sesquiterpenoids, triterpenoids, polyacetylenes, coumarins, phenylpropanoids, flavonoids and flavonoid glycosides, steroids, benzoquinones, and polysaccharides. Crude extracts and pure compounds of A. macrocephala are used to treat gastrointestinal hypofunction, cancer, arthritis, osteoporosis, splenic asthenia, abnormal fetal movement, Alzheimer disease, and obesity. These extracts have various pharmacological effects, including anti-tumor activity, anti-inflammatory activity, anti-aging activity, anti-oxidative activity, anti-osteoporotic activity, neuroprotective activity, and immunomodulatory activity, as well as improving gastrointestinal function and gonadal hormone regulation. Conclusions A. macrocephala is a valuable traditional Chinese medicinal herb with multiple pharmacological activities. Pharmacological investigations support the traditional use of A. macrocephala , and may validate the folk medicinal use of A. macrocephala to treat many chronic diseases. The available literature shows that much of the activity of A. macrocephala can be attributed to sesquiterpenoids, polysaccharides and polyacetylenes. However, there is a need to further understand the molecular mechanisms and the structure-function relationship of these constituents, as well as their potential synergistic and antagonistic effects. Further research on the comprehensive evaluation of medicinal quality, the understanding of multi-target network pharmacology of A. macrocephala , as well as its long-term in vivo toxicity and clinical efficacy is recommended. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Engineering vaccine-based therapeutics for infectious diseases is highly challenging, as trial formulations are often found to be nonspecific, ineffective, thermally or hydrolytically unstable, and/or toxic. Vaccines have greatly improved the therapeutic landscape for treating infectious diseases and have significantly reduced the threat by therapeutic and preventative approaches. Furthermore, the advent of recombinant technologies has greatly facilitated growth within the vaccine realm by mitigating risks such as virulence reversion despite making the production processes more cumbersome. In addition, seroconversion can also be enhanced by recombinant technology through kinetic and nonkinetic approaches, which are discussed herein. Recombinant technologies have greatly improved both amino acid-based vaccines and DNA-based vaccines. A plateau of interest has been reached between 2001 and 2010 for the scientific community with regard to DNA vaccine endeavors. The decrease in interest may likely be attributed to difficulties in improving immunogenic properties associated with DNA vaccines, although there has been research demonstrating improvement and optimization to this end. Despite improvement, to the extent of our knowledge, there are currently no regulatory body-approved DNA vaccines for human use (four vaccines approved for animal use). This article discusses engineering DNA vaccines against infectious diseases while discussing advantages and disadvantages of each, with an emphasis on applications of these DNA vaccines. Statement of Significance This review paper summarizes the state of the engineered/recombinant DNA vaccine field, with a scope entailing "Engineering DNA vaccines against infectious diseases". We endeavor to emphasize recent advances, recapitulating the current state of the field. In addition to discussing DNA therapeutics that have already been clinically translated, this review also examines current research developments, and the challenges thwarting further progression. Our review covers: recombinant DNA-based subunit vaccines; internalization and processing; enhancing immune protection via adjuvants; manufacturing and engineering DNA; the safety, stability and delivery of DNA vaccines or plasmids; controlling gene expression using plasmid engineering and gene circuits; overcoming immunogenic issues; and commercial successes. We hope that this review will inspire further research in DNA vaccine development. [ABSTRACT FROM AUTHOR]

Since the first immunomodulatory antibody was licensed by the FDA in 2011 for treating melanoma it has remained the case that only a certain proportion of cancer patients respond favourably to a particular therapy. Recent results from combining two or more different antibodies each targeting a different immune checkpoint indicate that the proportion of responding patients can be increased, but thus far there are no such therapies routinely yielding clinical benefit in 100% of patients in any cancer type. Therefore, predicting which patients will respond to a particular therapy remains of the utmost importance in order to maximise treatment efficacy and minimise side-effects and costs. Moreover, determining biomarkers predicting responses may provide insight into the mechanisms responsible for success or failure of that therapy. This article reviews seminal papers mostly from the past two years of progress in this area of intense investigation, and mostly in melanoma, the tumour type for which the largest body of data exists thus far. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a blood-borne pathogen which has chronically infected people worldwide. Therefore, it is of utmost importance to design prophylactic and therapeutic vaccine in order to control HCV infection. To date, several researchers have attempted to improve the efficiency of HCV vaccine by using different adjuvants. However, a few studies have focused on the synthetic immunomodulatory drugs as adjuvants for HCV vaccine. Recently, researchers have shown that lenalidomide, which is used to treat the patients with multiple myeloma, is capable of improving the immune system factors. In this paper, two doses of lenalidomide along with pcDNA3.1 + NS3 as HCV DNA vaccine were administrated in mice models and the percentage of regulatory T cells (Treg cells) and the cells with PD-1 + expression in spleen of mice model were investigated by flow cytometry method. Additionally, activities of CTL cells and NK cells were evaluated in spleen of prophylactic and therapeutic mice models via LDH method. Results of the Treg and PD-1 analysis showed that low dose of lenalidomide along with pcDNA3.1 + NS3 can noticeably decrease the percentage of Treg cells and the cells with PD-1 + expression, while lenalidomide can significantly increase the CTL and NK activity in mice models. Also, results of the therapeutic mice model, in which SP2/0 cells- challenged mice were treated with 5 mg/kg lenalidomide in combination with pcDNA3.1 + NS3, reasonably agreed with those of the prophylactic model. Finally, it was found that lenalidomide can reduce the level of Treg cells which results in lower the cells with PD-1 + expression and subsequently higher CTL and NK cell activities. This study concluded that lenalidomide possess the characteristics of an ideal adjuvant candidate for use in combination with HCV DNA vaccine in order to promote the immune response and vaccine efficiency. [ABSTRACT FROM AUTHOR]

Immunotherapy has recently emerged as a promising treatment for multiple myeloma (MM). There are now several monoclonal antibodies that target specific surface antigens on myeloma cells or the checkpoints of immune and myeloma cells. Elotuzumab (targeting SLAMF7), daratumumab (targeting CD38), and pembrolizumab (targeting PD-1) have shown clinical activity in clinical studies with relapsed/refractory MM. Dendritic cell vaccination is a safe strategy that has shown some efficacy in a subset of myeloma patients and may become a crucial part of MM treatment when combined with immunomodulatory drugs or immune check-point blockade. Genetically engineered T cells, such as chimeric antigen receptor T cells or T cell receptor-engineered T cells, have also shown encouraging results in recent clinical studies of patients with MM. In this paper, we discuss recent progress in immunotherapy for the treatment of MM. [ABSTRACT FROM AUTHOR]

Introduction: The diffuse epidermal exfoliation seen in Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) is similar to skin loss in second degree burns, and many of these patients are referred for treatment at burn centers. Treatment can differ markedly from center to center, and mortality can range from 25% to 70%, including a considerable morbidity. However, our experience over a 15-year period from 2000 to 2015 with 40 patients found a mortality rate of only 10% (4/40). The purpose of this paper is to discuss our treatment algorithm as a model for other centers treating SJS/TENs patients.Methods: Records were reviewed for all patients admitted to the LAC+USC burn unit between 2000 and 2015 and 40 patients were identified with biopsy-proven SJS or TENS. These cases were reviewed for age, gender, initial and greatest TBSA, causative drug, pre-existing medical conditions, and morbidity and mortality. All data were entered into the SPSS statistical software package and all statistical analyses were performed using this program.Results: Our treatment algorithm focused on early referral to a specialty burn unit, immediate discontinuation of the offending drug, fluid resuscitation, nutritional supplementation, and meticulous wound care. Average time to transfer to a burn unit was 3.36 days. Silver-releasing antimicrobial dressings were applied to the affected skin surface and changed every 3 days. Mupirocin coated petroleum gauze was used for facial involvement. Steroids were tapered and discontinued if initiated at an outside facility (58% of patients), and starting after 2001, all patients received a course of IVIG. All patients received fluid resuscitation and the majority received supplemental tube feedings (69%). Average length of total stay was 17.1 days and length of ICU stay 15.9 days. While 44% were transferred to another facility for further rehabilitative care, 37% of patients discharge to home. In patients discharged home with complete resolution of skin lesions, time to healing was an average of 14 days.Discussion: With our 10% mortality rate in 40 patients, our study represents a relatively large study population while maintaining a relatively low mortality rate. The demographic data from our study largely aligns with the existing literature, and we therefore feel that our low mortality rate is due to our treatment algorithm, rather than to a less severe pathology in our patient population. This claim is supported by a standard mortality ratio of 1.68. This ratio proves a significantly improved mortality than would be expected based on disease severity on admission. [ABSTRACT FROM AUTHOR]

Created with BioRender.com [Display omitted] Cancer immunity is dependent on dynamic interactions between T cells and dendritic cells (DCs). Polymer-based nanoparticles target DC receptors to improve anticancer immune responses. In this paper, DC surface receptors and their specific coupling natural ligands and antibodies are reviewed and compared. Moreover, reaction mechanisms are described, and the synergistic effects of immune adjuvants are demonstrated. Also, extracellular-targeting antigen-delivery strategies and intracellular stimulus responses are reviewed to promote the rational design of polymer delivery systems. [ABSTRACT FROM AUTHOR]

[Display omitted] • TME and glycolysis promote the occurrence and metastasis of tumors. • The mRNA vaccine activates CTL, cooperative NK, and M1 cells to improve the TIME. • Using vectors enhances the anti-tumor effect of the mRNA vaccine by improving TIME. • An mRNA vaccine combined with adjuvants or ICIs inhibits tumor metastasis. With the increasing threat of tumors to humans, mRNA vaccine-based immunotherapy has received extensive attention; however, the killing effect is sometimes unsatisfactory. The occurrence of tumors is closely related to the abnormality of the tumor immune microenvironment, including the increase in the number of immunosuppressive cells, the anomaly of some cells with tumor-killing function, and the increase in the glycolysis pathway, all of which will affect the anti-tumor effect of mRNA vaccines. Furthermore, delivery in the body and successful escape from lysosome are also essential steps that involve the result of killing. Starting from inhibiting tumor growth and metastasis by mRNA vaccines, this paper summarizes the tumor microenvironment constructed by immunosuppressive cells and cytokines, which inhibit immune cells from exerting anti-tumor effects, emphasizing the increase of glycolytic pathway after tumor formation, which makes tumors have a high probability of metastasis. In the present study, mRNA vaccines adjust the number of immune cells by combining adjuvants or immune checkpoint inhibitors (ICIs), thereby improving the tumor immune microenvironment (TIME) and tilting the balance in favor of immune-potent cells can achieve better anti-tumor effects. All efforts to understand the relationship between TIME and mRNA vaccine will provide a basis for tumor treatment in the future. [ABSTRACT FROM AUTHOR]

The immune repertoire (IR) refers to the sum of B cells and T cells with functional diversity in the circulatory system of one individual at any given time. Immune cells, which reside within microenvironments and are responsible for protecting the human body, include T cells, B cells, macrophages, and dendritic cells. These dedicated immune cells have a characteristic structure and function. T and B cells are the main lymphocytes and are responsible for cellular immunity and humoral immunity, respectively. The T cell receptor (TCR) and B cell receptor (BCR) are composed of multiple peptide chains with antigen specificity. The amino acid composition and sequence order are more diverse in the complementarity-determining regions (including CDR1, CDR2 and CDR3) of each peptide chain, allowing a vast library of TCRs and BCRs. IR research is becoming increasingly focused on the study of CDR3 diversity. Deep profiling of CDR3s using high-throughput sequencing is a powerful approach for elucidating the composition and distribution of the CDR3s in a given sample, with in-depth information at the sequence level. Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. To identify novel biomarkers for diagnosis and drug targets for therapeutic interventions, several groups attempted to describe immune repertoire characteristics of the liver in the physiological environment or/and pathological conditions. This paper reviews the recent progress in IR research on human diseases, including hepatocellular carcinoma, attempting to depict the relationships between hepatocellular carcinogenesis and the IR, and discusses the possibility of IR as a potential biomarker and therapeutic for hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Senegalese sole ( Solea senegalensis ) is a highly valued flatfish that grows well with diets containing plant ingredients but their effects on immune competence is still a matter of debate. The current study aimed to examine changes in innate immune parameters and gut microbiota in Senegalese sole fed with 35% or 72% of plant ingredients with or without probiotic or yeast supplementation. Overall, fish fed diets with 72% of plant ingredients showed lower transcript levels of key immune- and stress-related genes in distal intestine, rectum and head-kidney than the 35% diets. In particular, hsp90b mRNA levels in distal intestine were down-regulated by 70% and 60% with the use of high content of plant ingredients in the diet containing the multispecies probiotic and autolyzed yeast, respectively. Denaturing gradient gel electrophoresis showed lower similarity values for distal intestine than rectum. Also fish fed high content of plant ingredients displayed lower similarity values, pointing to a difference in the microbial populations between fish fed different plant ingredient contents on the diet. Our data revealed that inclusion of plant ingredients was associated with differences in gene expression and a more diverse microbiota profile but without a significant effect on growth performance. Moreover, probiotic supplementation resulted in up-regulation of hsp90b , gpx , cat and apoa1 transcript levels in distal intestine concomitantly with a growth rate reduction compared to non-supplemented fish. Statement of relevance There is an increasing trend in the aquaculture industry to replace fishmeal for plant ingredients, as a means of promoting sustainability of the industry. This paper contributes significantly to our limited knowledge of how plant ingredients and supplements affect gut microbiota and immunocompetence. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The genus Boerhavia is widely distributed in tropical, subtropical and temperate regions of the world including Mexico, America, Africa, Asia, Indian Ocean Islands, Pacific Islands and Australia. The genus Boerhavia is extensively used by local peoples and medicinal practitioners for treatments of hepatitis, urinary disorders, gastro intestinal diseases, inflammations, skin problems, infectious diseases and asthma. Present review focused on traditional uses, phytochemistry, pharmacology and toxicology of Boerhavia genus to support potential scope for advance ethnopharmacological study. Materials and methods Information on the Boerhavia species was collected from classical books on medicinal plants, pharmacopoeias and scientific databases like PubMed, Scopus, GoogleScholar, Web of Science and others. Also scientific literatures based on ethnomedicinal surveys, Ph.D. and M.Sc. dissertations, published papers from Elsevier, Taylor and Francis, Springer, ACS as well as Wiley publishers and reports by government bodies and documentations were assessed. Results A total of 180 compounds from Boerhavia genus were isolated of which B. diffusa alone shared around 131 compounds and for most of which it is currently an exclusive source. In the genus, phenolic glycosides and flavonoids contribute approximately 97 compounds. These includes eupalitin, rotenoids like boeravinones, coccineons, alkaloid i.e. betanin and punarnavine etc., showing vital pharmaceutical activities such as anticancer, anti-inflammatory, antioxidant and immunomodulatory. Conclusion Boerhavia is an important genus with wide range of medicinal uses. However, most of the available scientific literatures have lacked relevant doses, duration and positive controls for examining bioefficacy of extracts and its active compounds. In some studies, taxonomic errors were encountered. Moreover, there is need for accurate methods in testing the safety and ethnomedicinal validity of Boerhavia species. [ABSTRACT FROM AUTHOR]

The adjuvant effects of poly I:C and imiquimod during immunization with a recombinant protein, rVP28 derived from white spot syndrome virus (WSSV) was investigated in kuruma shrimp ( Marsupenaeus japonicus ). Shrimps were injected intramuscularly with different doses of rVP28, poly I:C and imiquimod, and combined rVP28 + poly I:C or imiquimod, and challenged with WSSV. Expression of innate immune-related genes was examined in the heart and lymphoid organ of combined rVP28 + poly I:C or imiquimod immunized shrimps at 1, 3 and 7 days after WSSV challenge. Shrimps which received rVP28 + poly I:C and rVP28 + imiquimod had significantly higher survivals of 52 and 58%, respectively compared to the rVP28 alone or PBS injected control groups ( P < 0.05). A significant up-regulation of innate immune-related genes, such as Rab7, lysozyme, penaeidin, crustin, Toll and TNF was noticed in combined rVP28 + poly I:C or imiquimod immunized shrimps. Our results indicate that injection administration of poly I:C or imiquimod + sub-unit protein (rVP28) provides a significant protection and induces immune response in kuruma shrimps against WSSV. Therefore, poly I:C and imiquimod have potentials to be used as adjuvants or immunostimulants in shrimp immunization. Statement of relevance Major contributors to economic losses in shrimp aquaculture are viral diseases, of which white spot syndrome virus (WSSV) is the most important one due to its rapid spread and economic impact. In this paper, we present an immunization method towards prevention of WSSV disease in kuruma shrimp using adjuvants such as poly I:C or imiquimod along with a sub-unit protein (rVP28). [ABSTRACT FROM AUTHOR]

The mechanism behind the adjuvant effect of aluminum salts is poorly understood notwithstanding that aluminum salts have been used for decades in clinical vaccines. In an aqueous environment and at a nearly neutral pH, the aluminum salts form particulate aggregates, and one plausible explanation of the lack of information regarding the mechanisms could be the absence of an efficient method of tracking phagocytosed aluminum adjuvants and thereby the intracellular location of the adjuvant. In this paper, we want to report upon the use of lumogallion staining enabling the detection of phagocytosed aluminum adjuvants inside viable cells. Including micromolar concentrations of lumogallion in the culture medium resulted in a strong fluorescence signal from cells that had phagocytosed the aluminum adjuvant. The fluorescence appeared as spots in the cytoplasm and by confocal microscopy and co-staining with probes presenting fluorescence in the far-red region of the spectrum, aluminum adjuvants could to a certain extent be identified as localized in acidic vesicles, i.e., lysosomes. Staining and detection of intracellular aluminum adjuvants was achieved not only by diffusion of lumogallion into the cytoplasm, thereby highlighting the presence of the adjuvant, but also by pre-staining the aluminum adjuvant prior to incubation with cells. Pre-staining of aluminum adjuvants resulted in bright fluorescent particulate aggregates that remained fluorescent for weeks and with only a minor reduction of fluorescence upon extensive washing or incubation with cells. Both aluminum oxyhydroxide and aluminum hydroxyphosphate, two of the most commonly used aluminum adjuvants in clinical vaccines, could be pre-stained with lumogallion and were easily tracked intracellularly after incubation with phagocytosing cells. Staining of viable cells using lumogallion will be a useful method in investigations of the mechanisms behind aluminum adjuvants' differentiation of antigen-presenting cells into inflammatory cells. Information will be gained regarding the phagosomal pathways and the events inside the phagosomes, and thereby the ultimate fate of phagocytosed aluminum adjuvants could be resolved. [ABSTRACT FROM AUTHOR]

Despite the effectiveness of surgery or radiation therapy for the treatment of early-stage prostate cancer (PCa), there is currently no effective strategy for late-stage disease. New therapeutic targets are emerging; in particular, dsRNA receptors Toll-like receptor 3 (TLR3) and cytosolic helicases expressed by cancer cells, once activated, exert a pro-apoptotic effect in different tumors. We previously demonstrated that the synthetic analog of dsRNA poly(I:C) induces apoptosis in the androgen-dependent PCa cell line LNCaP in a TLR3-dependent fashion, whereas only a weak apoptotic effect is observed in the more aggressive and androgen-independent PCa cells PC3 and DU145. In this paper, we characterize the receptors and the signaling pathways involved in the remarkable apoptosis induced by poly(I:C) transfected by Lipofectamine (in-poly(I:C)) compared with the 12-fold higher free poly(I:C) concentration in PC3 and DU145 cells. By using genetic inhibition of different poly(I:C) receptors, we demonstrate the crucial role of TLR3 and Src in in-poly(I:C)-induced apoptosis. Therefore, we show that the increased in-poly(I:C) apoptotic efficacy is due to a higher binding of endosomal TLR3. On the other hand, we show that in-poly(I:C) binding to cytosolic receptors MDA5 and RIG-I triggers IRF3-mediated signaling, leading uniquely to the upregulation of IFN-β, which likely in turn induces increased TLR3, MDA5, and RIG-I proteins. In summary, in-poly(I:C) activates two distinct antitumor pathways in PC3 and DU145 cells: one mediated by the TLR3/Src/STAT1 axis, leading to apoptosis, and the other one mediated by MDA5/RIG-I/IRF3, leading to immunoadjuvant IFN-β expression. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa , the major pathogen involved in lethal infections in cystic fibrosis (CF) population, is able to cause permanent chronic infections that can persist over the years. This ability to chronic colonize CF airways is related to a series of adaptive bacterial changes involving the immunostimulant lipopolysaccharide (LPS) molecule. The structure of LPSs isolated from several P. aeruginosa strains showed conserved features that can undergo chemical changes during the establishment of the chronic infection. In the present paper, we report the elucidation of the structure and the biological activity of the R-LPS (lipooligosaccharide, LOS) isolated from the persistent CF isolate P. aeruginosa strain RP73, in order to give further insights in the adaptation mechanism of the pathogen in the CF environment. The complete structural analysis of P. aeruginosa RP73 LOS was achieved by chemical analyses, NMR spectroscopy and MALDI MS spectrometry, while the assessment of the biological activity was attained testing the in vivo pro-inflammatory capacity of the isolated LOS molecule. While a typical CF LPS is able to trigger a high immune response and production of pro-inflammatory molecules, this P. aeruginosa RP73 LOS showed to possess a low pro-inflammatory capacity. This was possible due to a singular chemical structure possessing an under-acylated lipid A very similar to the LPS of P. aeruginosa found in chronic lung diseases such as bronchiectstasis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Liposomes self-assembled from lipids are excellent targeted transport carrier materials. • Lipids have the role of immune stimulation, which can stimulate the effect of innate immunity. • Liposomes combined with targeted transport and immunostimulatory effects have great advantages in cancer vaccines. Cancer is still a major threat for human life, and the cancer immunotherapy can be more optimized to prolong life. However, the effect of immunotherapy is not encouraging. In order to achieve outstanding immune effect, it is necessary to strengthen antigens uptake of antigen presenting cells. Adjuvants were added to vaccines to achieve this purpose, which could be divided into two types: as an immunostimulatory molecule, the innate immunities of the body were triggered; or as a delivery carrier, and antigens were cross-delivery through the "cytoplasmic pathway" and released at a specific location. This paper reviewed the relevant research status of tumor vaccine immune adjuvants in recent years. Among the review, the function, combination strategies and derivatives of lipid A were discussed in detail. In addition, some suggestions on the existing problems and research direction of lipids as tumor vaccine adjuvants were put forward. [ABSTRACT FROM AUTHOR]

The genus Orobanche consists of annual, biennial or perennial fleshy parasitic herb species, many of which are in use as traditional medicines and wild gathered foods since a long time. Recently, Orobanche spp. are increasingly accepted as edible medicines with nourishing properties. However, there is a lack of comprehensive understanding of their ethnopharmacological background. Aim of the review : This review focuses on the advancements in botanical classification, and summary of traditional use, phytochemistry, pharmacology and toxicology of Orobanche species, in order to check for scientific support of their traditional uses and the safe treatment of human ailments and diseases. In this review, the results of a systematic and comprehensive literature survey about Orobanche spp over the past 60 years (from 1960 to 2020) is presented. The selected literature includes periodicals, doctoral dissertations, master dissertations conference papers and various books. The literature was identified through search engine websites and a cross-checked with the Chinese pharmacopeia, classic Chinese and European herbals, regional medicinal monographs, and online ethnobotanical databases. The literature about the traditional uses revealed that Orobanche spp. were used as medicine and food in many regions of the world, but mainly in China and North America while in Europe they were primarily used as food items. Phenylpropanoid derivatives and alkaloids, were reported as their main bioactive compounds, showing antioxidant, immune system enhancing, androgenic, antibacterial and antiviral properties. Orobanche spp. are increasingly being used for tonic purposes in China. Their ethnopharmacological background suggests potential usages as healthy foods and food supplements. They have the potential to be developed into herbal medicines for tonifying the kidney, against impotence and spermatorrhea, dermatological problems and wounds, as well as infantile diarrhoea. However, the pharmacological studies conducted with extracts derived from Orobanche spp. were not useful for rationally explaining the traditional uses. More investigations are required to provide a pharmacological basis for the traditional claims and the relationship between traditional uses, clinical uses, phytochemistry and pharmacological properties. Additionally, quality control should be emphasized to ensure the safe and effective use of Orobanche derived products. Image 1 [ABSTRACT FROM AUTHOR]

• Adjuvant CV13 could prepare stable W/O/W emulsion by one-step emulsification. • Adjuvant CV13 containing GSLS had shown a good immune synergistic effect. • FMD vaccine prepared with CV13 containing GSLS induced high level of immune response. There has been an increasing interest in finding new formulations that qualify as vaccine adjuvants, which must be safe, stable, and have the capacity to stimulate a strong immune response. In this study, a basic formulation of a water-in-oil-in-water (W/O/W) adjuvant CV13 was developed, and ginseng stem-leaf saponins (GSLS) were added as an immune booster into oil phase. The physicochemical properties of the adjuvant were tested. Furthermore, the immune activity and the adjuvant effects, as indicated by the foot-and-mouth disease virus (FMDV) antigen were evaluated. The results showed that CV13 was similar in appearance to ISA 206 and could package FMDV antigen into a stable W/O/W emulsion. The FMD vaccine prepared with CV13 alone or CV13 containing GSLS achieved pharmaceutical characteristics comparable to a vaccine prepared with ISA 206, moreover the structural stability of the CV 13 vaccine was found to be better. Mice that were immunized with the FMD vaccine prepared with CV13 containing GSLS presented a significantly higher LPBE antibody titer and splenocyte proliferation rate than those immunized with a vaccine prepared with CV13 alone (p < 0.05). In addition, there was no significant difference between the groups that were immunized with FMD vaccine prepared with CV13 containing GSLS and ISA206 in terms of cellular and humoral immune response. In this paper, CV13 containing GSLS shows excellent immunologic adjuvant effect in mice model, and this new adjuvant may provide a potential choice for FMD vaccine production in the future. [ABSTRACT FROM AUTHOR]

Sauropus androgynus L. Merr is an underexploited perennial shrub traditionally used as a medicinal plant in South Asia and Southeast Asia. The plant is regarded as not just a green vegetable for diet, but as a traditional herb for certain aliments. For instance, it has traditionally been used to relieve fever, to treat ulcers and diabetes, to promote lactation and eyesight, and to reduce obesity. This paper aims to review the botany, phytochemistry, ethnopharmacology, and pharmacological activities of S. androgynus , and discuss the known chemical constituents at work in S. androgynus -induced bronchiolitis obliterans for providing new ideas to the mechanism of the disease and pharmacology research of the plant. The data presented in this review were collected from published literatures as well as the electronic databases of PubMed, CNKI, Web of Science, SCI finder, ACS, Science Direct, Wiley, Springer, Taylor, Google Scholar, and a number of unpublished resources, (e.g. books, and Ph.D. and M.Sc. dissertations). The scientific literature indicates that S. androgynus is a valuable and popular herbal medicine whose nutritional value is also higher than that of other commonly used vegetables. Phytochemical analyses identified high content of fatty acids, flavonoids, and polyphenols as the major bioactive components in S. androgynus. Crude extracts and phytochemical compounds isolated from S. androgynus show a wide spectrum of in vitro and in vivo pharmacological activities such as antioxidant, anti-inflammatory, anti-ulcer, skin whitening, anti-diabetic, and immunoregulatory activities. The traditional use, such as increasing lactation, treating ulcers and diabetes, and reducing obesity, have been evaluated and studied with various methods. Numerous reports have revealed the unusual link between the consumption of S. androgynus and the induction of a chronic and irreversible obstructive disease (namely, bronchiolitis obliterans), indicating that the toxicity and side effects of this plant that is presently used in health care and medicine are a major area of concern. Though little importance was attached to this green plant, S. androgynus has notable phytochemical constituents and various pharmacological activities including antioxidant, anti-inflammatory, and anti-obesity activities. Studies have firmly established the association between excessive consumption of the uncooked S. androgynus juice over a period of time and the occurrence of bronchiolitis obliterans. It is inadvisable to ingest excessive amounts of S. androgynus before fully understanding the pathogenesis and induction mechanism of this fatal disease. The phytochemistry of S. androgynus , its pharmacology for traditional use, S. androgynus -induced bronchiolitis obliterans still need further investigation. [ABSTRACT FROM AUTHOR]