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.

New Erra with Auto-Haemotherapy

The active researchers, till now, did not find a curative treatment for many diseases threatening lives of the patients. Proper management and treatment for those patients can give them longer and healthier lives. Over the years, auto-haemotherapy has been used to treat illnesses and diseases such as： arterial circulatory disorders, autoimmune diseases as rheumatoid arthritis, gout, bronchitis, allergies, ache vulgaris, skin eczema, leg ulcers, chronic sinusitis, skin lesions, HIV infection, HCV, Lyme disease, connective tissue diseases, fibromyalgia, asthma, history of heart attack and fungal infections. It helps in cessation of smoking, treatment of drug and alcohol addiction, decreasing the appetite, losing weight in obese patients and speeding up the recovery after a long period of illness. It has also been used in combination with conventional cancer treatment. Auto-haemotherapy is a simple technique where the blood is drawn from a vein and re-injected into a muscle. The blood in the muscle works as a foreign body that will be rejected by the reticulo-endothelial system. It stimulates the immune system and the bone marrow to increase the production of macrophages which are the body＇s cleaners. The macrophages cleanse everything, they eliminate bacteria, viruses, cancerous cells called neoplastic cells, this is a spring cleaning, and they even eliminate fibrin which is a clotted blood. Auto-haemotherapy is a very powerful technique with a low cost. It requires a syringe and a physician who knows how to withdraw blood from a vein and straight away does an intra-muscular injection with this blood under aseptic condition which increases and stimulates the immune system. Minor auto-haemotherapy technique was applied to 176 patients suffering from different diseases such as： Type I diabetes mellitus, bronchial asthma, chronic sinusitis, allergic conjunctivitis, allergic rhinitis, skin problems （vesicles, eczema, ulcer）, finger nail problem （infection, paronychia）, acne vulgaris, gastro-intestinal tract problem, lactose intolerance, connective tissue disease, AFS （adrenal fatigue syndrome）~ myasthenia gravis, fibromyalgia, gout, generalized osteoarthritis, joint osteoarthritis, low back pain with MODIC changes Type 1 on MRI （with or without spinal canal stenosis）, auto-immune diseases （ankylosing spondylitis, rheumatoid arthritis）, and infectious vaginal discharge. Also it has been applied to patients in order to stop smoking, and to other patients in order to lose weight. Results showed that the patients suffering from the previous different diseases improved significantly after being treated with auto-haemotherapy. In addition, the heavy smokers were able to decrease dramatically the number of cigarettes they were smoking, and the obese patients were able to lose their weight and they had less appetite.

Role of myelin auto-antigens in pain:a female connection

Following injury to the peripheral nerve,pain secondary to low threshold innocuous mechanical stimulation（mechanical allodynia）is commonly observed.Its origins are poorly understood and the pain is often refractory to common analgesic therapeutics.The past two decades has brought major advances in our understanding of the complexity of systems that underlie processing of neuropathic pain（pain arising from damage or disease of the somatosensory system）.

Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer,although it is limited by the low tumor delivery efficacy of anticancer drugs.Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect;however,excessively generated immunogenicity will cause serious inflammatory response syndrome.Here,we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts(LP@BG@CCM)by layer-by-layer encapsulation for the treatment of metastatic lung cancer.The preparation processes were simple,only involving film formation,electroporation,and pore extrusion.LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells.In the 4T1 breast cancer metastatic lung cancer mouse models,the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance,the reduced lung weight,the clear lung tissue structure,and the enhanced cancer cell apoptosis compared to its precursors.Moreover,several major immune factors were improved after administration of LP@BG@CCM,including the CD4^(+)/CD8a^(+)T cells in the spleen and the TNF-α,IFN-γ,and IL-4 in the lung.LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy,which is a promising medication for the treatment of metastatic lung cancer.

Immune Responses to Varicella-Zoster Virus Glycoprotein E Formulated with Poly(Lactic-co-Glycolic Acid) Nanoparticles and Nucleic Acid Adjuvants in Mice

The subunit herpes zoster vaccine Shingrix is superior to attenuated vaccine Zostavax in both safety and efficacy,yet its unlyophilizable liposome delivery system and the limited supply of naturally sourced immunological adjuvant QS-21 still need to be improved.Based on poly(lactic-co-glycolic acid)(PLGA)delivery systems that are stable during the lyophilization and rehydration process and using a double-emulsion(w/o/w)solvent evaporation method,we designed a series of nanoparticles with varicella-zoster virus antigen glycoprotein E(VZV-g E)as an antigen and nucleic acids including polyinosinic-polycytidylic acid(Poly I:C)and phosphodiester Cp G oligodeoxynucleotide(Cp G ODN),encapsulated as immune stimulators.While cationic lipids(DOTAP)have more potential than neutral lipids(DOPC)for activating g E-specific cell-mediated immunity(CMI)in immunized mice,especially when g E is encapsulated in and presented on the surface of nanoparticles,PLGA particles without lipids have the greatest potential to induce not only the highest g Especific Ig G titers but also the strongest g E-specific CMI responses,including the highest proportions of interferon-c(IFNc)-and interleukin-2(IL-2)-producing CD4?/CD8?T cells according to a flow cytometry assay and the greatest numbers of IFN-c-and IL-2-producing splenocytes according to an enzyme-linked immunospot(ELISPOT)assay.These results showed that immune-stimulating nucleic acids together with the PLGA delivery system showed promise as a safe and economical varicella and zoster vaccine candidate.

Litopenaeus vannamei immunestimulated with Macrocystis pyrifera extract:improving the immune response against Vibrio campbellii

Objective:To examine the immune responses of Litopenaeus vannamei after different treatments with a hot water extract of Macrocystis pyrifera(M.pyrifera)and a subsequent challenge with Vibrio campbellii(V.campbellii).Methods:A total of 184 adult white shrimp that were infected with V.campbellii(1×10^(6) CFU/shrimp)were immunostimulate by the hot-water extract from M.pyrifera via either injection(10μg)or immersion(350 mg/L),the experimental controls were injected with either saline solution or V.campbellii(1×10^(6) CFU/shrimp).The bacterial DNA depuration rate,antimicrobial activity and total hemocyte count were evaluated in hemolymph samples at 2,6,12,24,48 and 72 h post-infection.Results:Injected shrimp(10μg M.pyrifera extract)demonstrated the best clearance of bacterial infection,with 82%survival at 72 h post-infection(cellular response).Hemolymph from the immersed organisms had the best antimicrobial activity against Escherichia coli growth;specifically,the most efficient antimicrobial activity was observed at 24 h post-infection.Both types of immunostimulated shrimp had similar total hemocyte counts at 24 h post-infection(1.63-1.59 million/mL);however,after 72 h,injected shrimp had higher total hemocyte counts than immersed animals(2.59 v.s.0.56 million/mL).Conclusions:The injection of the M.pyrifera hot-water extract facilitated a more efficient response to V.campbellii infection due to the stimulation of the hemocytes of the shrimp.In other words,the cellular immune response was more efficient to eliminate bacterial infection than the humoral response in shrimp.

The progress and perspective of nanoparticle-enabled tumor metastasis treatment

As one of the most serious threats to human being,cancer is hard to be treated when metastasis happens.What’s worse,there are few identified targets of metastasis for drug development.Therefore,it is important to develop strategies to prevent metastasis or treat existed metastasis.This review focuses on the procedure of metastasis,and first summarizes the targeting delivery strategies,including primary tumor targeting drug delivery,tumor metastasis targeting drug delivery and hijacking circulation cells.Then,as a promising treatment,the application of immunotherapy in tumor metastasis treatment is introduced,and strategies that stimulating immune response are reviewed,including chemotherapy,photothermal therapy,photodynamic therapy,ferroptosis,sonodynamic therapy,and nanovaccines.Finally,the challenges and perspective about nanoparticle-enabled tumor metastasis treatment are discussed.

Multifunctional inorganic nanomaterials for cancer photoimmunotherapy

Phototherapy and immunotherapy in combination is regarded as the ideal ther-apeutic modality to treat both primary and metastatic tumors.Immunother-apy uses different immunological approaches to stimulate the immune system to identify tumor cells for targeted elimination.Phototherapy destroys the pri-mary tumors by light irradiation,which induces a series of immune responses through triggering immunogenic cancer cell death.Therefore,when integrat-ing immunotherapy with phototherapy,a novel anti-cancer strategy called pho-toimmunotherapy(PIT)is emerging.This synergistic treatment modality can not only enhance the effectiveness of both therapies but also overcome their inherent limitations,opening a new era for the current anti-cancer therapy.Recently,the advancement of nanomaterials affords a platform for PIT.From all these nanomaterials,inorganic nanomaterials stand out as idealmediators in PIT due to their unique physiochemical properties.Inorganic nanomaterials can not only serve as carriers to transport immunomodulatory agents in immunotherapy owing to their excellent drug-loading capacity but also function as photother-mal agents or photosensitizers in phototherapy because of their great optical characteristics.In this review,the recent advances of multifunctional inorganic nanomaterial-mediated drug delivery and their contributions to cancer PIT will be highlighted.

New understanding of the low-dose radiation-induced hormesis

Dr.Liu Shuzheng as a well-known educator and radiobiologist has started to work on the physiological benefits of low-dose radiation since 1970s.His research on the distinct effects of low-dose radiation from those of high-dose radiation has nationally and internationally impacted radiobiology,medicine and oncology.Therefore,here we briefly review the research from his research team from early years to last two decades.Two important facts related to LDR biological effects are the hormesis and adaptive response,both have been the main focuses of Dr.Liu Shuzheng early research.In the last couple of decades Dr.Liu Shuzheng have further investigated how to apply these important mechanisms into clinical translational research,such as the potential to application of LDRhormesis to enhance tumor’s chemo-or radio-therapy and LDR-induced adaptive response to protect normal tissue from chemo-or radio-therapy related side toxic effects.Therefore,Dr.Liu has provided important guidance and role model for his trainees in the continue of their research career in radiation biology,medicine and oncology.