Changes In Major Organs Research Articles

Investigation on parasitic infestation of Labeo rohita (Hamilton, 1822) in the south-western region of Bangladesh.

Our investigation focused into Labeo rohita, commonly known as Rui, a freshwateraquatic species in Bangladesh. Despite their nutritional significance, these fish faced a pressing challenge: parasite infections threaten the economic stability of the aquaculture sector. The present study aimed to investigate the parasite and histological changes in major organs of L. rohita, collected fromKhulna region - Dumuria, Paikgacha and Rupsha. About 180 (30/month) specimens were collected between the month of March and August 2023 to observe the parasitic status in L. rohita. Through microscopic examination, a total of 323 parasites were uncovered, spanning categories including Cestode, Nematode, Acanthocephala, Trematode and Digenia, predominantly residing in the intestines of L. rohita. The highest prevalence rate (70%) was recorded in both March and May 2023, with peak mean intensity observed in July (3.73). Notably, the highest mean abundance (2.37) exhibited in July and index of infestation (45.34) in June. Histological analysis confirmed parasitic infestations in the gastrointestinal region, with displaying histological changes within major organs such as the liver, kidney, gills, spleen and testicles due to parasitic infection. This study concluded that the indentified six categories of parasite and the affect of parasitic infestation in major organs of L. rohita within the study period. Urgent efforts to implement effective strategies for controlling the parasite infections in aquaculture to ensure the sustainable production of this invaluable fish species.

Design and therapeutic application of trans‐sodium crocetinate‐loaded cyclodextrin metal–organic frameworks as an enteric preparation for treating chronic heart failure

Chronic heart failure (CHF) arises from structural and functional changes in the myocardial tissue attributable to various etiologies. Crocetin and its derivative trans‐sodium crocetinate (TSC) have exhibited cardioprotective attributes; however, their poor aqueous solubility and bioavailability impede clinical development. This study aimed to construct a cyclodextrin metal–organic frameworks (CDMOFs)‐based oral delivery system to enhance the pharmacokinetic profile and therapeutic efficacy of TSC for CHF treatment. TSC was loaded into the synthesized γ‐CDMOFs via vacuum adsorption. The CDMOFs@TSC formulation was characterized and evaluated in vitro. Pharmacokinetic and pharmacodynamic analyses were performed in beagle dogs and CHF rats induced by coronary artery ligation, respectively. Both TSC and CDMOFs@TSC elicited no discernible toxicity or pathological changes in major organs of rats, providing preliminary evidence for their biosafety. Pharmacokinetic study in beagle dogs demonstrated that CDMOFs@TSC capsules markedly increase the relative oral bioavailability by 198% versus free TSC capsules. In rats afflicted with CHF, the administration of CDMOFs@TSC yielded notable enhancements in cardiac function. Additionally, it precipitated a reduction in biomarkers linked to myocardial injury, manifested anti‐inflammatory and antifibrotic effects, and induced alterations in myocardial energy metabolism. This is the first report of CDMOFs‐based oral delivery to improve the TSC bioavailability and efficacy. The utilization of CDMOFs@TSC resulted in superior therapeutic outcomes in comparison to standalone TSC by optimizing pharmacokinetics and precise targeted delivery. These results highlight the clinical potential of CDMOF as porous carriers to enable oral delivery of natural products for CHF therapy.

Membrane vesicles derived from Listeria monocytogenes might be a potential antigen delivery vector

Membrane vesicles (MVs) derived from Listeria monocytogenes (LM) have a natural nanoscale size and contain a variety of bacterial components. We speculated that LM MVs may be a novel delivery vector, but it is necessary to evaluate the safety and immunogenicity of LM MVs in vivo. Here, we isolated LM MVs and tested their safety and immunogenicity both in vitro and in vivo. The results showed that LM MVs stimulated RAW264.7 cells and DC2.4 cells to secrete the inflammatory cytokines IL-1β, TNF-α, IL-6 and IL-10. Intraperitoneal injection of LM MVs at 80 μg per C57BL/6 mouse did not cause lethal effects or irreversible pathological changes in major organs, indicating that LM MVs were safe. Intraperitoneal immunization of C57BL/6 mice twice with LM MVs mainly induced a high level of LM MV-specific IgG antibodies. In addition, we subcutaneously injected C57BL/6 mice with a mixture of ovalbumin and LM MVs and found that LM MVs exhibited a humoral immune adjuvant effect equal to that of the same amount of alum. The results of this study indicated that LM MVs have good safety and effective immunogenicity and may act as humoral immune adjuvants. Therefore, LM MVs are a potential new choice for antigen and drug delivery vectors.

Arterial Hypertension and the Hidden Disease of the Eye: Diagnostic Tools and Therapeutic Strategies.

Hypertension is a major cardiovascular risk factor that is responsible for a heavy burden of morbidity and mortality worldwide. A critical aspect of cardiovascular risk estimation in hypertensive patients depends on the assessment of hypertension-mediated organ damage (HMOD), namely the generalized structural and functional changes in major organs induced by persistently elevated blood pressure values. The vasculature of the eye shares several common structural, functional, and embryological features with that of the heart, brain, and kidney. Since retinal microcirculation offers the unique advantage of being directly accessible to non-invasive and relatively simple investigation tools, there has been considerable interest in the development and modernization of techniques that allow the assessment of the retinal vessels’ structural and functional features in health and disease. With the advent of artificial intelligence and the application of sophisticated physics technologies to human sciences, consistent steps forward have been made in the study of the ocular fundus as a privileged site for diagnostic and prognostic assessment of diverse disease conditions. In this narrative review, we will recapitulate the main ocular imaging techniques that are currently relevant from a clinical and/or research standpoint, with reference to their pathophysiological basis and their possible diagnostic and prognostic relevance. A possible non pharmacological approach to prevent the onset and progression of retinopathy in the presence of hypertension and related cardiovascular risk factors and diseases will also be discussed.

Advances in forensic diagnosis of electric shock death in the absence of typical electrical marks.

Electrical injury is a relatively uncommon but potentially devastating form of multi-system injury with high morbidity and mortality. In common electric injury cases, it is usually difficult to find characteristic changes of electric injury in major organs by using routine histopathological test methods unless there are landmark traces of electric injury, known as electric marks. How to determine electric shock death, especially in the absence of typical electrical marks on the body surface in some cases (which account for about two-thirds of electric injury cases), remains a challenging problem in forensic practice. Our summary shows that many current related studies have focused their efforts to find characteristic histopathological changes in major organs of the body caused by electric injury. Based on the results obtained through comparison of the literature, we find that it may be more urgent and important to find the optimal autopsy or sampling sites in cases with no typical electric marks, knowing that these sites may often reflect the most significant histopathological changes of electric injury, for instance anatomy and sampling of the anterior wrist and the medial malleolus in cases involving the hand-to-foot electric circuit pathway. In this article, we make a summary of advances in identification methods of electric injury, hoping that it could provide some new insights for further research in this field.

Extracellular Vesicles from Akkermansia muciniphila Elicit Antitumor Immunity Against Prostate Cancer via Modulation of CD8+ T Cells and Macrophages.

PurposeProstate cancer (PCa) is one of the most common malignancies in males. Despite the success of immunotherapy in many malignant cancers, strategies are still needed to improve therapeutic efficacy in PCa. This study aimed to investigate the effects of Akkermansia muciniphila-derived extracellular vesicles (Akk-EVs) on PCa and elucidate the underlying immune-related mechanism.MethodsAkk-EVs were isolated by ultracentrifugation and intravenously injected to treat syngeneic PCa-bearing immune-competent mice. Immunophenotypic changes in immune cells, such as cytotoxic T lymphocytes and macrophages, were measured via flow cytometry analysis. Histological examination was used to detect morphological changes in major organs after Akk-EVs treatments. In vitro, flow cytometry was performed to confirm the effects of Akk-EVs on the activation of CD8+ T cells. Quantitative PCR and immunofluorescence staining were carried out to test the impact of Akk-EVs on macrophage polarization. Cell counting kit-8 (CCK-8) analysis, colony formation assays, and scratch wound healing assays were conducted to assess the effects of Akk-EVs-treated macrophages on the proliferation and invasion of PCa cells. CCK-8 assays also confirmed the impact of Akk-EVs on the viability of normal cells.ResultsIntravenous injection of Akk-EVs in immune-competent mice reduced the tumor burden of PCa without inducing obvious toxicity in normal tissues. This treatment elevated the proportion of granzyme B-positive (GZMB+) and interferon γ-positive (IFN-γ+) lymphocytes in CD8+ T cells and caused macrophage recruitment, with increased tumor-killing M1 macrophages and decreased immunosuppressive M2 macrophages. In vitro, Akk-EVs increased the number of GZMB+CD8+ and IFN-γ+CD8+ T cells and M1-like macrophages. In addition, conditioned medium from Akk-EVs-treated macrophages suppressed the proliferation and invasion of prostate cells. Furthermore, the effective dose of Akk-EVs was well-tolerated in normal cells.ConclusionOur study revealed the promising prospects of Akk-EVs as an efficient and biocompatible immunotherapeutic agent for PCa treatment.

Development and Characterization of Saturated Fatty Acid-Engineered, Silica-Coated Lipid Vesicular System for Effective Oral Delivery of Alfa-Choriogonadotropin.

The present study was designed to develop an efficient, safe, and patient-friendly dosage form, for oral delivery of alfa-choriogonadotropin, used in the treatment of female reproductive infertility. Silica-coated, saturated fatty acid (dipalmitoylphosphatidylcholine (DPPC))-engineered, nanolipidic vesicular (NLVs) system was developed for systemic delivery of therapeutic peptide, alfa-choriogonadotropin, through oral route. DPPC-based NLVs were formulated using the technique of thin-film hydration and were coated with silica to form a homogeneous surface silica shell. The formulated silica-coated NLVs were evaluated for physicochemical and physiologic stability under simulated conditions and were optimized based on physicochemical parameters like particle size, zeta potential, polydispersity index (PDI), entrapment efficiency, and in vitro release profile. Silica-coated, DPPC-based NLVs imparted physicochemical stability to entrapped alfa-choriogonadotropin against the biological environment prevailing in the human gastrointestinal tract (GIT). In vivo, subchronic animal toxicity studies were performed to assess the safety of the designed dosage form. Results of in vitro characterization and in vivo pharmacokinetic studies of fabricated formulation revealed that the silica-coated, DPPC-based NLV formulation was not only stable in human GIT but was also as efficacious as a marketed parenteral formulation for the systemic delivery of alfa-choriogonadotropin. In vivo toxicity studies revealed that silica-coated NLVs did not alter hematological and serum biochemical parameters. The histopathological studies also depicted no macroscopic changes in major organs; thus, the developed formulation was proven to be nontoxic and equally efficient as a marketed parenteral formulation for the delivery of alfa-choriogonadotropin with added benefits of possible self-medication, more patient acceptability, and no chances of infection.

Non-invasive delivery of levodopa-loaded nanoparticles to the brain via lymphatic vasculature to enhance treatment of Parkinson’s disease

Levodopa (L-DOPA), a precursor of dopamine, is commonly prescribed for the treatment of the Parkinson’s disease (PD). However, oral administration of levodopa results in a high level of homocysteine in the peripheral circulation, thereby elevating the risk of cardiovascular disease, and limiting its clinical application. Here, we report a non-invasive method to deliver levodopa to the brain by delivering L-DOPA-loaded sub-50 nm nanoparticles via brain-lymphatic vasculature. The hydrophilic L-DOPA was successfully encapsulated into nanoparticles of tannic acid (TA)/polyvinyl alcohol (PVA) via hydrogen bonding using the flash nanocomplexation (FNC) process, resulting in a high L-DOPA-loading capacity and uniform size in a scalable manner. Pharmacodynamics analysis in a PD rat model demonstrated that the levels of dopamine and tyrosine hydroxylase, which indicate the dopaminergic neuron functions, were increased by 2- and 4-fold, respectively. Movement disorders and cerebral oxidative stress of the rats were significantly improved. This formulation exhibited a high degree of biocompatibility as evidenced by lack of induced inflammation or other pathological changes in major organs. This antioxidative and drug-delivery platform administered through the brain-lymphatic vasculature shows promise for clinical treatment of the PD.

Evaluation of time passed since death by examination of oxidative stress markers, histopathological, and molecular changes of major organs in male albino rats.

Recent biochemical, metabolic, and molecular profiles of various body fluids showed more accurate correlation to the postmortem interval than the traditional physical examination. Our study aimed to evaluate time passed since death in relation to oxidative stress markers, HMGB1 genetic expression, histopathological examination, and BCL2 immunohistochemical analysis in major organs (heart, kidney, and testis). Forty-two adult male rats were included and randomly divided into seven equal groups. After sacrification, the rodents were kept at room temperature and major organs were obtained at 0, 12, 24, 48, 72, 96, and 120h. Malonaldehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH) tissue levels, High mobility group box 1 protein (HMGB1) gene expression, histopathological, and B cell lymphoma 2 (BCL2) immunohistochemical expressions were analyzed. Postmortem interval was correlated to different tissue levels of MDA, SOD, and GSH. HMGB1 showed enhanced postmortem gene expression with a peak at 48h after death. Obvious time-dependent histopathological changes were observed in all the examined organs. Dilated spaces, extravasation, and fragmentation scores in heart specimens were higher at 96 and 120h compared with the other groups. Renal changes in the form of shrunken glomeruli, loss of tubular epithelium, and hyalinization and testicular findings in the form of epithelial detachment, vacuolation, and loss of sperms started at 72h postmortem. BCL2 expression began to decrease 24h and became negative at 96h after death. In conclusion, HMGB1 gene expression can be used for estimation of time passed since death as it shows time-dependent changes in the form of a progressive increase with a peak at 48h then it begins to decline. Oxidants and antioxidants are correlated to PMI until 120h after death. Histopathological changes in the heart, kidney, and testis are also time-dependent until the 5th day after death. BCL2 immunohistochemical expression begins to decline 24h until 96h after death when it becomes negative.

Green synthesis of zinc oxide nanoparticles by Neem extract as multi-facet therapeutic agents

This study was designed to develop green synthesized zinc oxide nanoparticles (ZnO-NPs) as potential nano-antibiotics against drug resistant microbes along with multifarious biomedical applications. The developed ZnO-NPs with an average size of 19.57 ± 1.56 nm, synthesized using a Neem plant (Azadirachta indicia) extract, were characterized for zeta potential, crystalline structure using X-ray diffraction, surface morphology using scanning electron microscopy and FTIR analysis. The ZnO-NPs demonstrated a far superior antioxidant and enzyme inhibition activity with a significantly lower IC50 value as compared to a standard reference. Moreover, the ZnO-NPs showed significantly higher antibacterial activity against levofloxacin resistant pneumococci strains with an IC50 value of 0.014 μM compared to 2.048 mM for that of levofloxacin. An in vivo acute toxicity study in mice showed slight changes in liver functional tests, especially renal functional tests, compared to that of the control group. Complete blood analysis showed no significant changes. Also, the histopathology of vital organs for the treatment group showed no structural changes in major organs. Overall, the results suggested that the present green synthesized Neem based ZnO-NPs could be developed as a therapeutic agent with antioxidant, enzyme inhibition and strong antibacterial potential against antibiotic-resistant bacteria that can be safely administered.

Doxorubicin and CD‑CUR inclusion complex co‑loaded in thermosensitive hydrogel PLGA‑PEG‑PLGA localized administration for osteosarcoma.

Combination therapy is a promising and prevalent strategy for osteosarcoma treatment. Curcumin (CUR), as a chemosensitizer, improves the antitumor effect of first-line chemotherapy drugs. However, due to its poor solubility and instability in physiological conditions, the bioavailability of CUR is limited. In order to improve the physicochemical properties of natural CUR, β-cyclodextrin was adopted to generate a β-cyclodextrin curcumin (CD-CUR) inclusion complex. A thermosensitive hydrogel, poly(D,L-lactide-co-glycolide)-poly(ethylene-glycol)-poly(D,L-lactide-co-glycolide), was selected and synthesized to co-deliver doxorubicin (DOX) and CD-CUR to tumor sites. The dual-drug delivery system (gel+DOX+CD-CUR) was prepared by mixing drugs with hydrogels and had a perfect sol-gel phase transition temperature (18.3°C for 20% concentration). Both DOX and CUR were released from hydrogels in a sustained manner in PBS (pH 7.4) medium. The combination therapy based on DOX+CD-CUR exhibited higher antitumor activity than monotherapies in vitro. Combined CD-CUR therapy significantly downregulated Bcl-2 expression and upregulated caspase-3 expression, suggesting that DOX combined with CD-CUR treatment has a higher apoptosis-inducing efficiency. The antitumor efficiency of the gel+DOX+CD-CUR strategy was evaluated in K-7 tumor-bearing mice, and this localized combination therapy demonstrated a higher antitumor efficiency compared with free DOX+CD-CUR or single-drug strategies. There were no significant differences in body weight and histological changes of major organs in each group. Therefore, the present combination treatment based on hydrogel may be a feasible approach to co-deliver DOX and CD-CUR to osteosarcoma tumor sites in clinical practice.

Does established vascular kidney disease exist?

Does established vascular kidney disease exist?

GCMS analysis of sadagura (smokeless tobacco), its enhanced genomic instability causing potential due to arsenic co-exposure, and vitamin-C supplementation as a possible remedial measure: a study involving multiple model test systems

North-eastern states of India, including Assam, have a high prevalence of head and neck cancer cases. In these regions, Sadagura is a unique form of smokeless tobacco (SLT). There are fewer reports regarding the effects of simultaneous sadagura and arsenic co-exposure. Analysis of chemical compounds present in sadagura aqueous extract was done using gas chromatography–mass spectrometry. Estimation of arsenic contamination in groundwater and bioaccumulation in human tissues was performed by using atomic absorption spectroscopy. Buccal micronucleus cytome (BMCyt) assay and analysis of various peripheral blood parameters were performed among study volunteers. Chronic exposure (90 days) experiments were performed in mice test system in vivo to determine any possible protective potential of vitamin C (Vit-C) supplementation against sadagura and arsenic co-exposure. BMCyt assay results revealed a higher incidence of micronucleated cells (p < 0.001), and cell death biomarker among sadagura consumers residing in arsenic affected areas. Comet assay of mice femur bone marrow cells following chronic exposure of the test substances revealed a reduction in DNA damage due to Vit-C supplementation. Histological examination of the hepatic and renal tissues revealed marked improvement due to Vit-C supplementation in mice against sadagura and arsenic chronic co-exposure. Indiscriminate consumption, presence of various harmful compounds in sadagura along with arsenic co-exposure might be a vital link for the higher incidence of oral cancer in the region. Chronic Vit-C supplementation study results in mice show its effective remedial potential against combined sadagura and arsenic co-mediated genotoxicity and ultrastructural changes in major organs.

Classical swine fever virus C-strain with eight mutation sites shows enhanced cell adaptation and protects pigs from lethal challenge.

Control of classical swine fever (CSF) in developing countries is achieved by immunization with attenuated vaccines, such as the lapinized C-strain vaccine that has been widely used in China. However, C-strain has relatively low growth rate in cell cultures, thus affecting productivity of the vaccine for the industry. In this study, eight amino acid residues were mutated on the C-strain backbone, resulting in a cell-adapted strain Cmut8. The mutant strain exhibited rapid growth with titer of about 100 fold higher than its parental C-strain. The mutation sites located at structural proteins Erns and E2 contributed more to cell adaptation than those located in non-structural proteins. Sera collected from pigs inoculated with Cmut8 and C-strain at the same dose showed similar antibody levels and neutralization titers. Pigs inoculated with different doses of Cmut8 (low, medium and high) and with C-strain offered full protection against challenge with a virulent strain, shown as absence of fever and other symptoms, marginal low levels of viral load, and no obvious gross pathological changes in major organs. Unvaccinated control pigs challenged with the virulent strain showed high fever from day 2 post-challenge and apparent clinical symptoms with two deaths. Viral load were markedly elevated in these control pigs after challenge. The pigs inoculated with high dose of Cmut8 did not show fever or other typical CSF symptoms, and no apparent pathological changes were observed in major organs. Besides, the Cmut8 strain did not induce typical fever response in rabbits. These results demonstrate that the cell-adapted Cmut8 strain remains non-pathogenic to the weaned pigs, provides full protection and could be a good candidate vaccine strain for improved yield at lower cost.

Acute and chronic toxicity of a polyherbal preparation \u2013 Jueyin granules

BackgroundThe potential toxicity of Chinese herbal medicine has attracted more attention in recent years. Jueyin granules (JYG), a polyherbal formula, have been proven to be an effective agent for treating psoriasis in both animal models and clinical research. However, little is known about the possible acute and chronic toxicity of JYG. The objective of this study was to investigate the safety of JYG in ICR mice and Wistar rats.MethodsTo examine the acute toxicity of JYG, ICR mice were randomly divided into an experimental group and a control group, each comprising 20 mice (10 male and 10 female). The experimental group was fed JYG solution at a dose of 21.5 g/kg, equivalent to 143 times the clinical human dosage, for 14 days, whereas control animals were fed distilled water. In the chronic toxicity test, Wistar rats were divided into four groups, each comprising 40 rats (20 male and 20 female). For 6 months, the experimental animals were given JYG at a dose of 7.5, 3.75 and 1.875 g/kg, whereas control animals were given distilled water. The animals’ body weight, food and water consumptions were monitored weekly. In addition, their biochemical and hematological parameters, histopathology, and body and organ weights were all measured at specific observation time points.ResultsAccording to the results of the acute toxicity test, no mortality was found and no abnormal pathological changes in major organs were observed in mice treated with JYG. In the chronic toxicity test, JYG did not cause significant abnormalities in the physiological parameters or pathological changes in the major organs of the rats.ConclusionThe results indicated that JYG at the given doses did not induce any harmful effects in animals. Thus, it is reasonable to conclude that JYG is safe at the studied dosage levels and causes no acute or chronic toxicity in animal models.

Barbaloin loaded polydopamine-polylactide-TPGS (PLA-TPGS) nanoparticles against gastric cancer as a targeted drug delivery system: Studies in vitro and in vivo

Gastric cancer is the third leading cause of cancer-associated death worldwide. Although a decrease in its incidence is observed, gastric cancer still poses a major clinical challenge due to poor prognosis and limited treatments. Barbaloin (BBL) is a main medicinal composition of the Chinese traditional medicine aloe vera. BBL has various bioactivities, including anti-oxidant, anti-inflammatory and anti-tumor properties. Polydopamine (pD)-based surface modification is easy to functionalize polymeric nanoparticles (NPs) surfaces with ligands and/or additional polymeric layers. In the present study, BBL-loaded formulations was developed with pD-modified NPs, which was synthesized by polylactide-TPGS (PLA-TPGS) (pD-PLA-TPGS/NPs). And galactosamine (Gal) was conjugated on the prepared NPs (Gal-pD-PLA-TPGS/NPs) for targeting the gastric cancer cells. Here, we found that BBL-loaded Gal-pD-PLA-TPGS/NPs showed the highest cellular uptake efficacy in gastric cancer cells. Gal-pD-PLA-TPGS/NPs more significantly reduced the gastric cancer cell viability. Further, greater apoptosis, autophagy and ROS generation was induced by Gal-pD-PLA-TPGS/NPs in gastric cancer cells. Additionally, compared to the other two NPs, Gal-pD-PLA-TPGS/NPs most markedly decreased ATP levels in gastric cancer cells. In vivo, Gal-pD-PLA-TPGS/NPs were specifically targeted to tumor site. Moreover, Gal-pD-PLA-TPGS/NPs exhibited the most anti-tumor effects, as evidenced by the lowest tumor volume and tumor weight. Of note, there was no significant difference was observed in body and liver weight, as well as the histological changes in major organs isolated from each group of mice. Together, the findings indicated that BBL-loaded Gal-pD-PLA-TPGS/NPs could be targeted to gastric cancer cells to suppress tumor progression without toxicity.

Multifunctional zinc-based hollow nanoplatforms as a smart pH-responsive drug delivery system to enhance in vivo tumor-inhibition efficacy

Novel multifunctional ZnO@ (Fe3O4/ZnS:Mn2+) nanocomposites as a pH-responsive drug delivery system were designed and successfully synthesized by a self-assembling method. The as-prepared ZnO@(Fe3O4/ZnS:Mn2+) possess porous hollow structure with strong orange fluorescence and faster magnetic response, which is beneficial for the functions of drug loading, fluorescence labeling and magnetic targeting simultaneously. Both in vitro and in vivo experiments testify that the ZnO@(Fe3O4/ZnS:Mn2+) nanocomposites own a good biocompatibility without obvious side effects on both cells and mice. After 24days of treatment on the mice, ZnO@(Fe3O4/ZnS:Mn2+) nanocomposites greatly inhibited the tumor growth without causing both body weight change and any obvious pathological changes in major organs. The better antitumor efficacy than free DOX can be ascribed to both the accumulation of DOX-ZnO@(Fe3O4/ZnS:Mn2+) inside tumor and a sustained DOX release due to the dissociation of ZnO@(Fe3O4/ZnS:Mn2+) in acidic environment.

Axl is not an indispensable factor for Zika virus infection in mice.

Recently, Zika virus (ZIKV) outbreak has been associated with a sharp increase in cases of Guillain–Barré syndrome and severe fetal abnormalities. However, the mechanism underlying the interaction of ZIKV with host cells is not yet clear. Axl, a receptor tyrosine kinase, is postulated as a receptor for ZIKV entry; however, its in vivo role during ZIKV infection and its impact on the outcome of the disease have not been fully characterized and evaluated. Moreover, there are contradictory results on its involvement in ZIKV infection. Here we utilized Axl-deficient mice (Axl−/−) and their littermates (Axl+/−) to study the in vivo role of Axl in ZIKV infection. Our results showed that both Axl+/− and Axl−/− suckling mice supported the replication of ZIKV and presented clinical manifestations. No significant difference has been found between Axl-deficient mice and their littermates in terms of the survival rate, clinical manifestations, viral load, ZIKV distribution and histopathological changes in major organs. These results therefore indicate that Axl is not an indispensable factor for ZIKV infection in mice.

Antitumor immunity induced by VE-cadherin modified DC vaccine.

Dendritic cells (DCs) are the most potent antigen-presenting cells. A strong interest has been developed in DC vaccines for cancer immunotherapy. Besides, angiogenesis is essential for tumor growth. VE-cadherin has a crucial function in various aspects of vascular biological functions. Here, we produced the full VE-cadherin gene modified DC vaccine (DC-VEC). Its antitumor immunity and chief mechanism driving antitumor effect was evaluated. Analyses were performed including test of antitumor antibody, CTL-mediated cytotoxicity experiment, vascular density, evaluation of the variation of cells and cytokines in immunoregulation. Its damage to the major organs was also evaluated. DC-VEC vaccine resulted in retarded tumor progression and prolonged survival in mice. In DC-VEC group, large amount of immunoglobulin was generated, T cells exhibited greater cytotoxicity against VE-cadherin, and tumor angiogenesis was suppressed. Besides, a decrease of VEGF-A and TGF-β1, and an increase of IL-4 and IFN-γ were observed. CD4+ and CD8+ T cells were higher, with increased IFN-γ secretion. The percentage of myeloid-derived suppressor cells and regulatory T cells decreased mildly. Also, it had no pathologic changes in major organs. DC-VEC vaccine represents a promising antitumor immunotherapy. The main mechanism is associated with its anti-angiogenesis and immunoregulation response.

Токсичний вплив глутамату натрію на живий організм

The article analyzes the available literature data on the problem of the food additives usage in the food industry. According to many scientists, reducing the amount of fresh foods that are eaten, and increasing of artificial additives may be one of reasons for increased prevalence of diseases such as cancer, diabetes mellitus, obesity, depression and asthma.Number of food additives used in food industry in different countries, is up to five hundred today, not counting the combined additives and flavorings. One of the most common food additive inUkraineand inEuropeis monosodium glutamate (E-621). Studies have shown that excess of sodium glutamate intake can provoke the development of hypertension and stroke, diabetes mellitus, Alzheimer's disease and abnormalities of the nervous system development, erosive lesions of the mucous membrane of the stomach and weight gain.There are no reliable data that showed in what doses and at what conditions monosodium glutamate which is used in foods constantly is harmful to health. On the one hand, there are studies that intake of monosodium glutamate in the dosage of3 gramsper day is dangerous to human health. However, other researchers argue that daily administration of sodium glutamate to rats even in safe for human health doses (15 and 30 mg/kg), corresponding to 1 and2 gramsfor the average adult person, has toxic effects.Thus, based on the large amount of data can be argued that today there is a constant increase in the use of food additives in the food industry of an economically developed countries as well as countries with low intake. And because food additives are foreign substances to the human body (due to the chemical composition or number) investigation of their effect on human health has become relevant. Moreover, small number of data on biochemical and morphological changes in major organs and body systems dictate the need for a detailed study of the problem. In addition, it is necessary to focus not only on the study of established dangerous doses of food additives, but also to study the molecular mechanisms of these substances influence on the living body in "safe" (permitted) doses.