The Immunogenic Connection of Thermal and Nonthermal Molecular Effects in Modulated Electro-Hyperthermia

Hyperthermia in oncology is an emerging complementary therapy. The clinical results depend on multiple conditional factors, like the type of cancer, the stage, the applied treatment device, and the complementary conventional therapy. The molecular effect could also be different depending on the temperature, heating dose, kind of energy transfer, and timing sequences compared to the concomitant treatment. This article examines the molecular impacts of a specific technique used in oncological hyperthermia called modulated electro-hyperthermia (mEHT). What sets mEHT apart is its emphasis on harnessing the combined effects of thermal and nonthermal factors. Nonthermal energy absorption occurs through the excitation of molecules, while the thermal component ensures the ideal conditions for this process. The applied radiofrequency current selects the malignant cells, and the modulation drives the nonthermal effects to immunogenic cell death, helping to develop tumor-specific antitumoral immune reactions. The synergy of the thermal and nonthermal components excites the lipid-assembled clusters of transmembrane proteins (membrane rafts) as the channels of transient receptor potentials (TRPs), the heat-shock proteins (HSPs), the voltage-gated channels, and the voltage-sensitive phosphatases (VSPs). All these transmembrane compartments channeling various ionic species (like calcium and proton) interact with the cytoskeleton and are involved in the apoptotic signal pathways.

Effects of the Chinese Medicinal Herb Com plex Additives on Non-specific Immunity of Amursturgeon( Acipenser schrencki Brandt)

This study was to investigate the effects of aqueous decotion from three Chinese medicinal herb additives （ Cyrtomium fortunei, prescription I and prescription II） on non-specific immunity of 1 ＋ age old Amur sturgeon （Acipenser schrencki Brandt） by oral perfusion. Cyrtomiumfortunei, prescription I and prescription II were orally given to 15 fishes for each experimental group once a day, with the concentration of 9,175 and 36 g/S0 kg body weight, respectively. The administration was lasted for 14 days. Meanwhile, distilled water was orally given as the control. After the experiment, some of the experimental fishes were stimulated with high temperature （30 ℃ ） for two hours. Sampling was performed from fishes treated at 22 ℃ and 30 ℃ for measuring the protein content in the serum, phagocytic activity of leucocytes and the activity of the lysozyme in six tissues. The results indicated that Cyrtomiumfortunei and prescription II could help to enhance the content of various proteins and the phagocytic activity of leucocytes. There was no significant change in the effects between these two additives at either the normal temperature or high temperature. Prescription I did not show an obvious effect on the immunity of fishes at the normal temperature, but it did in promo- ting high-efficiency response and improving immunoregulation of fish shocked by some stimuli.

Pembrolizumab autoimmune related diabetes:Moving forward,keep learning

Immune checkpoint inhibitors(and more specifically programmed cell death 1/programmed cell death ligand 1 inhibitors as Pembrolizumab)initiated a revolution in the field of melanoma and have now expanded to several tumor subtypes and in increasingly broader clinical contexts,including the adjuvant and neoadjuvant setting,with potentially curable patients and prolonged survival.The side effects related to these drugs include a wide spectrum of manifestations,with endocrinological adverse events being some of the most frequent.Pembrolizumab-induced type 1 diabetes mellitus is an infrequent but potentially serious and not clearly reversible side effect that possesses characteristic clinical features and has high morbidity and mortality,with a chronic impact on quality of life.The etiopathogenesis of this phenomenom needs to be further investigated and a collaborative effort through the involvement of oncologists and other medical specialists is necessary for the correct identification and management of patients at risk.

Astragalus polysaccharide enhances immunity and inhibits H9N2 avian influenza virus in vitro and in vivo

This study investigated the humoral immunization of Astragalus polysaccharide （APS） against HgN2 avian influenza virus （H9N2 AIV） infection in chickens. The effects of APS treatment on H9N2 infection was evaluated by an Mqq- [3（4, 5-dimethylthiazol-2-yl）-2, 3-diphenyl tetrazolium bromide] assay and analysis of MFIC and cytokine mRNA expression. The effect on lymphocyte and serum antibody titers in vivo was also investigated. IL-4, IL-6, IL-10, LITAF, IL-12 and antibody titers to H9N2 AIV wet enhanced in the first week after APS treatment. The results indicated that APS treatment reduces H9N2 AIV replication and promotes early humoral immune responses in young chickens.This study investigated the humoral immunization of Astragalus polysaccharide （APS） against HgN2 avian influenza virus （H9N2 AIV） infection in chickens. The effects of APS treatment on HgN2 infection was evaluated by an M]q- [3（4, 5-dimethylthiazol-2-yl）-2, 3-diphenyl tetrazolium bromide] assay and analysis of MHC and cytokine mRNA expression. The effect on lymphocyte and serum antibody titers in vivo was also investigated. IL-4, IL-6, IL-10, LITAF, IL-12 and antibody titers to PIgN2 AIV were enhanced in the first week after APS treatment. The results indicated that APS treatment reduces HgN2 AIV replication and promotes early humoral immune responses in young chickens.

Tracking Survey of Immune Effects of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome (HP-PRRS) in Changping District, Beijing City

The epidemiology of highly pathogenic porcine reproductive and respiratory syndrome( HP-PRRS) in Changping District,Beijing City was investigated from 2010 to 2015. Through statistics of vaccine,immune procedure and antibody levels,the epidemic prevention effect of HP-PRRS in Changping District was scientifically assessed.

Interpreting Dose-Response Relation for Exposure to Multiple Sound Impulses in the Framework of Immunity

Hearing loss is a common military health problem and it is closely related to exposures to impulse noises from blast explosions and weapon firings. In a study based on test data of chinchillas and scaled to humans (Military Medicine, 181: 59-69), an empirical injury model was constructed for exposure to multiple sound impulses of equal intensity. Building upon the empirical injury model, we conduct a mathematical study of the hearing loss injury caused by multiple impulses of non-uniform intensities. We adopt the theoretical framework of viewing individual sound exposures as separate injury causing events, and in that framework, we examine synergy for causing injury (fatigue) or negative synergy (immunity) or independence among a sequence of doses. Starting with the empirical logistic dose-response relation and the empirical dose combination rule, we show that for causing injury, a sequence of sound exposure events are not independent of each other. The phenomenological effect of a preceding event on the subsequent event is always immunity. We extend the empirical dose combination rule, which is applicable only in the case of homogeneous impulses of equal intensity, to accommodate the general case of multiple heterogeneous sound exposures with non-uniform intensities. In addition to studying and extending the empirical dose combination rule, we also explore the dose combination rule for the hypothetical case of independent events, and compare it with the empirical one. We measure the effect of immunity quantitatively using the immunity factor defined as the percentage of decrease in injury probability attributed to the sound exposure in the preceding event. Our main findings on the immunity factor are: 1) the immunity factor is primarily a function of the difference in SELA (A- weighted sound exposure level) between the two sound exposure events;it is virtually independent of the magnitude of the two SELA values as long as the difference is fixed;2) the immunity factor increases monotonically from 0 to 100% as the first dose is varied from being significantly below the second dose, to being moderately above the second dose. The extended dose-response formulation developed in this study provides a theoretical framework for assessing the injury risk in realistic situations.

Immunological effect of aqueous extract of Vernonia amygdalina and a known immune booster called immunace and their admixtures on HIV/AIDS clients:a comparative study

Objective:To investigate the immunological effect of Vernonia amygdalina(V.amygdalina) leaf extract and immunace on HIV infected patients taking highly active antiretrwiral therapy. Methods:Fresh V.amygdalina leaves were collected within Nsukka area in Enugu State.The leaves were rinsed with distilled water.Two handful of cleaned fresh leaves were soaked in 200 mL water and squeezed gently by hand to a mixture.Clients were divided into four groups and each group was given different combination.They took the medication for four weeks.The immune effect was tested against marketed immune booster in some retroviral clients.Results:The mean absolute CD4 count was increased in the client who took the extract or supplement.And the clients who took both the extract and supplement had a greater increase in the CD4 count.The increased CD4 was significant as compared with the control group(P<0.05).The skin rashes were also improved in the entire groups.Conclusions:It can be concluded that the aqueous extract of V.amygdalina and immunace or both have immunological effect on HIV infected patients. Therefore,we suggest that the V.amygdalina extract or immunace or both could be used as adjuvant in the management of HIV/AIDS clients.

Investigation of the immune effects of Scutellaria baicalensis on blood leukocytes and selected organs of the chicken＇s lymphatic system

Background： The health of chickens and the welfare of poultry industry are central to the efforts of addressing global food security. Therefore, it is essential to study chicken immunology to maintain and improve its health and to find novel and sustainable solutions. This paper presents a study on investigation of the effect of Scutellaria baicalensis root（SBR） on the immune response of broiler chicken, especially on lymphocytes and heterophils reactivity, regarding their contribution to the development of immunity of the chickens.Methods： The 121-day-old Hubbard Hi-Y male broiler hybrids were randomly assigned to four treatment groups,three SBR supplemented groups（0.5, 1.0, and 1.5% of SBR） and one control group. Each treatment was replicated five times with six birds per replicate pen in a battery brooder. Blood was collected after 3-（rd） and 6-（th）wk of the experiment, and hemoglobin and hematocrit values were determined, as well as total leukocyte count and differential count were performed. Nitroblue tetrazolium test and phagocytosis assay as nonspecific immune parameters and humoral immune responses to the antigenic challenge by sheep red blood cells were performed.Moreover, the ability of peripheral blood lymphocytes to form radial segmentation（RS） of their nuclei was analyzed.Body weight and relative weight of spleen, liver, and bursa of Fabricius were recorded.Results： Results showed that mean heterophile/lymphocyte ratio increased in the SBR groups compared to the control group and the blood of the chickens showed lymphocytic depletion. The results also demonstrated that the relative weight of bursa of Fabricius and spleen in groups fed with SBR significantly decreased compared to the control group. This study also showed that the addition of SBR significantly inhibited the formation of RS of nuclei compared to some cytotoxic substances.Conclusion： We found that SBR supplementation should be carefully evaluated when given to poultry. The excess intake of SBR supplementation may cause immunologic inhibition and may negatively affect the development of immune organs. SBR has inhibited the formation of radial segmentation nuclei showing antimetastatic properties and also the phagocytosis of chicken heterophils.

Immunogenicity and tumor-inhibiting effects of HSP-antigen peptide complex in melanoma B16 cells in mice

目的 :黑色素瘤 B1 6细胞热休克蛋白 -抗原肽复合物 (HACs)及其粗提物 (HAC- CEs)的制备 ,以及它们的免疫原性和抑瘤效应的研究。方法 :应用 Sephacryl S- 2 0 0凝胶过滤制备HAC- CEs,应用亲和层析纯化 HACs,并测其免疫功能和抑瘤效应。结果 :应用凝胶过滤制备的HAC- CE3、HAC- CE4、HAC- CE5和应用亲和层析纯化的 HAC60 ,HAC75和 HAC97均不同程度地降低肿瘤发生率、延迟肿瘤发生时间和减少移植黑色素瘤 C57BL/6J小鼠死亡率 ;同时 ,伴有小鼠脾细胞 IFN-γ和 IL- 2分泌活性及 CTL杀伤率的增加。结论 :分子量为 60 0 0 0～ 970 0 0的 HACs具有免疫原性和抑瘤效应 ,本研究为制备肿瘤疫苗提供重要的实验依据。

The immune-modulating effects of viable Weissella cibaria JW15 on RAW 264.7 macrophage cells

The objective of this study is to investigate the immune-enhancing ability of viable and heat-killed Weissella cibaria JW15(JW15)isolated from Kimchi in RAW 264.7 macrophages.The immune effects were evaluated by measuring the production of NO,cytokines,inflammatory enzyme,and activation of NF-κB.Viable JW15 executed higher activity on stimulating the release of TNF-αas well as activating NF-κB compared to that of heatkilled JW15.Additionally,viable and heat-killed JW15 significantly increased the production of NO,IL-6 and TNF-αmore than that of Lactobacillus rhamnosus GG(LGG).Furthermore,viable JW15 induced higher production of i NOS compared with that of viable LGG.Collectively,our finding indicates that viable JW15 had similar,if not more,immune-enhancing activities as heat-killed JW15.In addition,viable JW15 had higher immune-enhancing activity than commercial strain LGG.Therefore,viable JW15 has the potential to be used as a functional food to improve the host immune response.

Effects of Qishen Ultrafine Powder on Immune Efficacy in Chickens

[Objective] This paper aimed to observe the effects of Qishen ultrafine powder on immune efficacy of infectious bursal disease vaccine in chickens. [ Method] 360 1-day-old chickens were randomly divided into six groups equally, and group I -V were vaccinated with IBD live virus vaccine on the 21 th and 35th day, respectively. From 14th to 21th day, group I - Ⅲ were added with 1%, 0.5% of Qishen ultrafine powder and 2% of Qishan powder in basel diet, respectively, group IV was given Yupingfeng oral liquid and group VI was as a control group without vaccination. Be- fore the expedment （14-day-old chickens as DO ） and 7 （ D7 ）, 14 （ D14 ）, 21 （ D21 ）, 28 （ D26 ）, 35 （ D36 ）, 42 （ D42 ） days after the experiment, the dynamic change of serum IBD specific antibody was determined, respectively. On D7, D21 and D36, the dynamic change of peripheral T lymphocyte proliferation and IL-2 in serum were determined, respectively. The weight change was also observed. [Results] Compared with the immune control group, the immune effects of IBD vaccine of each administration group were significantly improved, and there was no significant difference between each other. [ Condusion] Qishen ultrafine powder could increase immune function of chickens at lower dosage.

Immune blockade inhibitors and the radiation abscopal effect in gastrointestinal cancers

The field of tumor immunology has produced in the recent years a revolution in cancer therapeutics putting an end in the long lasting frustration of investigators in the area stemming from largely unsuccessful strides to develop cancer vaccines. This progress has come from the introduction of immune checkpoint inhibitors, monoclonal antibodies blocking ligand/receptor pairs with inhibitory effects for immune cells. Through this blockade immune checkpoint blockers are able to ac-tivate the immune system and create an anti-tumoral effect. A significant sub-set of patients with various types of cancers such as melanoma, lung carcinomas and urothelial cancers benefit from treatment with these drugs and survivals have improved in some ca-ses. However other cancers are primarily resistant to immune blockers and secondary resistance is also the norm. Radiation therapy is often used in the palliative treatment of patients with advanced cancers and, in addition to the local effect in the irradiated field, it may in rare cases produce a systemic antitumor effect, termed "abscopal". This effect has been suggested to be produced by immune mechanisms. Thus an opportunity presents for a synergistic effect of immune stimulation between radiation and immune blockade inhibitors. The therapeutic opportunities presented with the combination of radiation and these drugs for gastrointestinal cancers will be discussed in this editorial overview.

RADIOIMMUNOTOXICOLOGICAL EFFECT OF ENRICHED URANIUM ON CENTRAL AND PERIPHERAL IMMUNE CELLS AND THE PROTECTIVE ACTION OF IL－1 AND IL－2

Accumulation of enriched 235U-UO2F2 in the body had injurious effects on theimmune function of central and peripheral immune cells. After an intravenousinjection of beaU--UO,F,, the spontaneous ’H--TdR incorporation in thymocytes andbone marrow cells decreased, with the thymocytes damaged more markedly. Theproliferation ability of spleen T and B lymphocytes were both inhibited, with Blymphocytes inhibited more severely. In spleen B lymphocytes the IL-- 1 production andIL--2 consumption were diminished. The inhibition of spleen B lymphocyteproliferation by 'U-- UOZFZ was partially restored by adding exogenous IL-- 1 or IL--2to the cultured lymphocytes obtained from 'U injected mice.

Systemic adverse effects and toxicities associated with immunotherapy:A review

Immunotherapy is rapidly evolving secondary to the advent of newer immunotherapeutic agents and increasing approval of the current agents by the United States Food and Drug Administration to treat a wide spectrum of cancers.Immunotherapeutic agents have gained immense popularity due to their tumorspecific action.Immunotherapy is slowly transforming into a separate therapeutic entity,and the fifth pillar of management for cancers alongside surgery,radiotherapy,chemotherapy,and targeted therapy.However,like any therapeutic entity it has its own adverse effects.With the increasing use of immunotherapeutic agents,it is vital for physicians to acquaint themselves with these adverse effects.The aim of this review is to investigate the common systemic adverse effects and toxicities associated with the use of different classes of immunotherapeutic agents.We provide an overview of potential adverse effects and toxicities associated with different classes of immunotherapeutic agents organized by organ systems,as well as an extensive discussion of the current recommendations for treatment and clinical trial data.As we continue to see increasing usage of these agents in clinical practice,it is vital for physicians to familiarize themselves with these effects.

IN VITRO ANTI-HEPATOMA EFFECTS OF MONOCYTES AND KUPFFER CELLS ISOLATED FROM HEPATOMA PATIENTS AFTER TREATMENT WITH BIOLOGICAL IMMUNE STIMULANTS

Monocytes (MC), lymphocytes (LC) and Kupffer cells (KC) were isolated respectively from blood and surgical liver samples of patients suffering from he-patocellular carcinoma (HCC). 13 patients were given BCG, mixed bacterium vaccine (MBV) and human white blood cell interferon (IFN), the other 3 patients were not treated with any biological immune stimulants (BIS) and served as controls. The cytosta-tic and cytotoxic effects of MC and KC on human hepatoma SMMC-7721 (TC) were assayed in vitro and the numbers of T total (Tt), T helper (Th) and T suppressor (Ts) cells were counted using CD monoclonal antibody immunofluorescence. The results were as follows: (1) On the 7th day after the first administration of BIS, the cytostatic and cytotoxic effects of MC on TC showed obvious increase over pre-administration. The activity of BIS was 1 ?5 times as high as that in the controls. (2) After 3 administrations, the cytostatic effect of MC on TC increased to the normal level (84%), while the controls remained as before (45%). (3) On the 7th day after first administration, cytostatic and cytotoxic effects of KC on TC were 0.5 and 1 times higher respectively than those of the controls. (4) The numbers of Tt and Th of patients given BIS increased continuously; on the contrary Ts decreased in number. These results indicate that combined use of BCG, MBV and IFN can actively enhance the immune anti-hepatoma function of patients suffering from HCC.

Changes of immune response and side effects before and after nutritional intervention in cervical cancer patients with concurrent chemoradiotherapy

Objective:To investigate the changes of immune response and side effects before and after nutritional intervention in cervical cancer patients with concurrent chemoradiotherapy. Methods: A total of 160 patients with primary cervical cancer who received concurrent chemoradiotherapy in this hospital between May 2016 and September 2017 were selected as the research subjects. Their nutritional intervention plans were reviewed and used to divide the patients into the control group (n=83) who accepted conventional nutritional support and the nutritional intervention group (n=77) who accepted targeted nutritional intervention. The differences in the contents of Th1/Th2 immunity indexes and humoral immunity indexes as well as the levels of bone marrow suppression-related indexes were compared between the two groups before and after intervention.Results: Before intervention, the differences in the contents of Th1/Th2 immunity indexes and humoral immunity indexes as well as the levels of bone marrow suppression-related indexes were not statistically significant between the two groups. After intervention, serum IL-2, IFN-γ, IL-4 and IL-6 contents of nutritional intervention group were lower than those of control group;serum IgA, IgM, IgG, C3 and C4 contents were higher than those of control group;peripheral blood WBC, RBC, Hb and PLT levels were higher than those of control group.Conclusion: Nutritional intervention can effectively optimize the immune status and reduce the bone marrow suppression reaction in cervical cancer patients with concurrent chemoradiotherapy.

EFFECT OF ACUPUNCTURE ON IMMUNE FUNCTION OF PATIENTS TREATED WITH RADIOTHERAPY AND CHEMOTHERAPY

In comparison with the normal people group, values of blood CD2+ and CD4+ in pa-tients with mallgnant tumors treated with radiotherapy and chemotherapy were significantly lower andthe ratio of CD助+ and CD8+ decreased obviously （all P【0.001）; CD8+ had no apparent change （P】0.05）. Following acupunctural treatment, values of CD2+,CD4+ and the ratio of CD4+ to CD8+ increasedobviously （all P【0.001）; while those of the medicinal control group had no significant change aftertreatment（P】0. 05）. Values of IgG, IgA and IgM in patients’ serum presented an abnormal de-creasing or increasing tendency, and C3 in minority of patients were raised. Results indicated thatthere was a biphasic regulatory effect of acupuncture on the disturbance of humoral immunity andcould correct the deviation of C3 level; and its effect was better than or similar to that of the medicinecontrol group. It demonstrates that acupuncture can enhance and regulate. the immune function of pa-tients treated with radiotherapy

Clinical effects investigation of continuous plasma filtration with adsorption and continuous hematodialysis on improving the immune level of patients with sepsis in ICU

Objective:To investigate the clinical effects of continuous plasma filtration with adsorption and continuous hematodialysis on improving the immune level of patients with sepsis in ICU. Methods:A total of 80 patients with sepsis were randomly divided into study group and control group, 40 patients in each group. All the patients were treated by routine treatment. Patients in study group were treated by continuous plasma filtration with adsorption and patients in control group were treated by continuous hematodialysis. The blood samples were collected before and after treatment. The immune cell level, inflammatory factors level, APACHEⅡ score and death rate were compared between two groups.Results:All immune cell indexes were significantly improved in both groups. All immune cell indexes in study group were significantly better than those in control group, after treatment. All inflammatory factors were significantly decreased in both groups. All inflammatory factors in study group were significantly better than those in control group, after treatment. The APACHEⅡ in study group was significantly better than that in control group, after treatment. The death rate in study group was significantly less than that in control group.Conclusion:Continuous plasma filtration with adsorption has a great clinical efficacy on patients with sepsis in ICU, which can improve the immune level and prognosis, makes it worth for clinical application.

Blood and Histopathological Biomarkers of Immune-related Adverse Effects of Treatment with Immune Checkpoint Inhibitors

Immune checkpoint inhibitors have been a recent major breakthrough in the management of tumors.They have broadened the scope of management in medical oncology,which has been heavily dependent on chemotherapy.Immune checkpoint inhibitors have renewed the hope of many patients for a more effective treatment.However,Immune checkpoint inhibitors are also associated with a variety of adverse effects,most commonly immunerelated adverse events,and these are often different from the known chemotherapy-induced toxicities.Hence,there is a need to identify specific biomarkers which are able to predict or diagnose these immune-related adverse events.

Research Progress of Anti-tumor Effects of Curcuma zedoaria and its Active Ingredients Through Immune Regulation Mechanism

The continuous increase in the incidence rate of various fatal malignant tumors in the recent years warrants an imperative search for medications or drugs with obvious anti-tumor eflects and reliable curative effects.Previous studies have found that Curcuma zedoaria and its active ingredients,such as turmeric oil,curcumol,and P-elemene,have obvious antitumor effects,and they do not have the adverse reactions and side effects seen in the anti-tumor drugs of Western medicine.Based on the review and inductive analysis of related literature,we summarize in the present article the results of some researchers who investigated the anti-tumor effects of Curcuma zedoaria and its active ingredients through the immune regulation mechanism.