Abstract: Vitamin D is essential for the regulation of the immune system. In recent years, the role of vitamin D in the control of several autoimmune conditions such as inflammatory bowel disease (IBD), celiac disease, type 1 diabetes mellitus (T1DM), and others has been investigated. The aim of this review was to define the level of knowledge on vitamin D's role in these disorders, as well as the preventive and therapeutic role of vitamin D supplementation. Relevant studies published over the last 20 years were identified via a PubMed/Medline (http://www.ncbi.nlm.nih.gov/pubmed/) search using the keywords: vitamin D, autoimmune disease, and prevention. Vitamin D deficiency or impaired function of the enzymes necessary for its activity has been shown to affect the onset and severity of the autoimmune diseases examined. Vitamin D supplementation appears useful in the support therapy of IBD. Its role in celiac disease, autoimmune hepatitis, T1DM, and autoimmune thyroiditis is unclear. In conclusion, further studies are needed to define whether vitamin D is a cause or a result of the most common autoimmune, extra-skeletal diseases, such as IBD. Vitamin D should be provided to all newborns during their first year of life. Afterwards, the vitamin D supplementation regimen should be tailored to the presence of risk factors for vitamin D deficiency and/or specific disease.

Abstract: Microplastic pollution and its impact on the ecological environment have attracted worldwide attention. The strong adsorption capacity of the microplastic surface plays an important role in the migration of microplastics throughout the environment. Synergistic effects between microplastics and persistent organic pollutants increase the toxicity of pollutants to organisms. In addition, microplastics cause different degrees of harm to aquatic organisms with different nutritional levels. However, the toxic effects of microplastics and organic pollutants on organisms, the distribution of microplastics in higher aquatic organisms, and the nutrient transfer in complex aquatic food webs require further research. Therefore, studying the impact of microplastics on the ecological environment would provide insights into controlling microplastic pollution. This paper in-depth discusses the source, distribution, and transmission of microplastics and summarizes the current situation of the impact of microplastics on the ecological environment, including physical, chemical, and biological effects. This paper also suggests topics for further research on the influence of microplastics on various aspects of the ecological environment.

Abstract: BACKGROUND In the present study, resveratrol was used to prepare complexes of cerium and nanoceria, also coated with gold (CeO2@Au core-shells) to improve the surface interactions in physiological conditions. METHODS The CeO2@Au core-shells were characterized using powder X-ray diffraction (PXRD), Fourier transforms infrared spectroscopy (FTIR), transmission electron microscope (TEM) analysis, dynamic light scattering (DLS) and ζ potential. RESULTS The experiment was led to the successful synthesis of nanosized CeO2@Au core-shells, although agglomeration of particles caused the distribution of the larger particles. The TEM analysis demonstrated the particles sizes ranged from 20 nm to 170 nm. Moreover, the PXRD analysis showed that both nanoceria and gold with the same crystal systems and space groups. To investigate the anticancer activity of the CeO2@Au core-shells, the cytotoxicity of the nanoparticles was investigated against liver cancerous cell lines (HepG2). CONCLUSIONS The results indicated biosynthesized NCs have significant cellular toxicity properties against HepG2 and could be utilized in hepatocarcinoma therapy. Further in vivo investigations is proposed to be designed to assess anti-cancer and safety effects of fabricated nanocomposites.

Abstract: DNA methylation plays an important role in the silence of tissue-specific genes to prevent them from being expressed in the wrong tissue. Aberrant DNA methylation (genome-wide hypomethylation and site-specific hypermethylation) are observed in many types of cancer. DNA methylation patterns are established and maintained through the combined actions of methyltransferase and demethylase, such as DNA methyltransferase (DNMT)-1, DNMT-3, and ten-eleven translocation (TET) family enzymes. It is well known that the process of tumor evolution is complicated with different hallmarks. Early findings put forward the model that focal hypermethylation of tumor suppressor genes (TSG) could straightly trigger transcriptional silencing and malignant transformation, whereas varying levels of DNA methylation also occur at other sites and can differently regulate gene expression and biological processes. The interplay of tumor and immune cells in the tumor microenvironment is complex. Understanding the role of DNA methylation in cancer immunity is critical to better navigate epigenetic agents. Furthermore, a greater understanding of the interaction of DNA methylation with tumor metabolic reprogramming would create a bright avenue for pharmacologic managements of malignancies. In this review, we will describe the molecular mechanisms of DNA methylation abnormalities in cancer biology, introduce the roles of DNA methylation patterns on cancer-immunity cycle and metabolic reprogramming, summarize modulators that are used in targeting DNA remodeling, and highlight the importance of combining epigenome-targeting drugs with other cancer therapies.

Abstract: BACKGROUND Microplastics (MPs) and Nanoplastics (NPs) are plastic fragments that spread in the environment and accumulate in the human body, so they have been becoming a worldwide environmental concern because of their potential human health effects. The aim of this systematic review was to investigate the prospective impact of MPs and NPs on the inflammatory process. METHODS Electronic article search was performed on PubMed, Scopus and Web of Science international databases from 1 Jan 2012 to 31 Dec 2021. Screenings of titles, abstracts and full texts were performed according to the Preferred Reporting Item for Systematic Review and Meta-analyses (PRISMA). The methodological quality of the studies was checked by the Toxicological data Reliability Assessment Tool. RESULTS Electronic article search identified 125 records, from which 6 in vitro, 11 in vivo and 2 both in vivo and in vitro studies were included. Both in vivo and in vitro studies have showed an increase ofdifferent inflammatory outcomes (Interleukines, Tumor necrosis factor, Chemokines, Interferones, Transcription factors, Growth factors, Oxydoreductase, Proteins and others), thus it seems to confirm the association withthe exposure to microplastics of different types, sizes, exposure times and exposed species. CONCLUSIONS This systematic review seems to support the relationship between the exposure to MPs and the inflammatory processboth in vivo and in vitro. Greater caution is needed about the role of NPs because ofa very small number of studies. Additional high-quality studies are warranted to confirm these results, especially the research should be focused on NPs being lacking literature.

Abstract: This study reviews the recent progress of machine learning for the early diagnosis of thyroid disease. Based on the results of this review, different machine learning methods would be appropriate for different types of data for the early diagnosis of thyroid disease: (1) the random forest and gradient boosting in the case of numeric data; (2) the random forest in the case of genomic data; (3) the random forest and the ensemble in the case of radiomic data; and (4) the random forest in the case of ultrasound data. Their performance measures varied within 64.3-99.5 for accuracy, 66.8-90.1 for sensitivity, 61.8-85.5 for specificity, and 64.0-96.9 for the area under the receiver operating characteristic curve. According to the findings of this review, indeed, the following attributes would be important variables for the early diagnosis of thyroid disease: clinical stage, marital status, histological type, age, nerve injury symptom, economic income, surgery type [the quality of life 3 months after thyroid cancer surgery]; tumor diameter, symptoms, extrathyroidal extension [the local recurrence of differentiated thyroid carcinoma]; RNA feasures including ADD3-AS1 (downregulation), MIR100HG (downregulation), FAM95C (downregulation), MORC2-AS1 (downregulation), LINC00506 (downregulation), ST7-AS1 (downregulation), LOC339059 (downregulation), MIR181A2HG (upregulation), FAM181A-AS1 (downregulation), LBX2-AS1 (upregulation), BLACAT1 (upregulation), hsa-miR-9-5p (downregulation), hsa-miR-146b-3p (upregulation), hsa-miR-199b-5p (downregulation), hsa-miR-4709-3p (upregulation), hsa-miR-34a-5p (upregulation), hsa-miR-214-3p (downregulation) [papillary thyroid carcinoma]; gut microbiota RNA features such as veillonella, paraprevotella, neisseria, rheinheimera [hypothyroidism]; and ultrasound features, i.e., wreath-shaped feature, micro-calcification, strain ratio [the malignancy of thyroid nodules].

Abstract: Background: Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson’s disease (PD). The first rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. More and more single nucleotide polymorphisms (SNPs) have been identified in a population of PD. However, little is known about the impact of genetic variations of the IDO on the pathogenesis of PD. Methods: SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. Results: No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. Conclusions: The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.

Abstract: Exosomes, a subset of extracellular vesicles, are widely present in various body fluids and are involved in mediating intercellular communication. They have received extensive attention as diagnostic markers. The excellent physicochemical and biological properties of exosomes make them great potential drug delivery vehicles for the treatment of cancer and other diseases. However, various challenges need to be addressed for the clinical application of exosomes. This review introduces the biogenesis and uptake of exosomes and compares different approaches for isolation and drug loading, focusing on the application and current challenges of exosomes as drug delivery vehicles in cancer therapy.

Abstract: In the present era of climate change and global warming, high temperatures have increased considerably, posing a threat to plant life. Heat stress affects the biochemistry, physiology and molecular makeup of the plant by altering the key processes, i.e., photosynthesis, respiration and reproduction which reduces its growth and development. There is a dire need to manage this problem sustainably for plant conservation as well as the food security of the human population. Use of phytohormones to induce thermotolerance in plants can be a sustainable way to fight the adversities of heat stress. Phytohormone-induced thermotolerance proves to be a compelling approach to sustainably relieve the damaging effects of heat stress on plants. Salicylic acid (SA) is an essential molecule in biotic and abiotic defense response signal transduction pathways. When supplied externally, it imparts heat stress tolerance to the plants by different means, viz., increased Heat Shock Proteins (HSP) production, Reactive oxygen species (ROS) scavenging, protection of the reproductive system and enhancing photosynthetic efficiency. The effect of SA on plants is highly dependent on the concentration applied, plant species, plant age, type of tissues treated, and duration of the treatment. The present review paper summarizes the mechanism of thermotolerance induced by salicylic acid in plants under heat stress conditions. It includes the regulatory effects of SA on heat shock proteins, antioxidant metabolism, and maintenance of Ca2+ homeostasis under heat stress. This review combines the studies conducted to elucidate the role of SA in the modulation of different mechanisms which lead to heat stress tolerance in plants. It discusses the mechanism of SA in protecting the photosynthetic machinery and reproductive system during high-temperature stress.

Abstract: Parkinson’s disease (PD) is a progressive, neurodegenerative condition of the central nervous system (CNS) affecting 6.3 million people worldwide with no curative treatments. Current therapies aim to mitigate PD’s effects and offer symptomatic relief for patients. Multiple pathways are involved in the pathogenesis of PD, leading to neuroinflammation and the destruction of dopaminergic neurons in the CNS. This review focuses on PD pathology and the role of calpain, a neutral protease, as a regulator of various immune cells such as T-cells, microglia and astrocytes which lead to persistent neuroinflammatory responses and neuronal loss in both the brain and spinal cord (SC). Calpain plays a significant role in the cleavage and aggregation of toxic α-synuclein (α-syn), a presynaptic neural protein, and other organelles, contributing to mitochondrial dysfunction and oxidative stress. α-Syn aggregation results in the formation of Lewy bodies (LB) that further contribute to neuronal damage through lipid bilayer penetration, calcium ion (Ca2+) influx, oxidative stress and damage to the blood brain barrier (BBB). Dysfunctional mitochondria destabilize cytosolic Ca2+ concentrations, raising intracellular Ca2+; this leads to excessive calpain activation and persistent inflammatory responses. α-Syn aggregation also results in the disruption of dopamine synthesis through phosphorylation of tyrosine hydroxylase (TH), a key enzyme involved in the conversion of tyrosine to levodopa (L-DOPA), the amino acid precursor to dopamine. Decreased dopamine levels result in altered dopamine receptor (DR) signaling, ultimately activating pro-inflammatory T-cells to further contribute to the inflammatory response. All of these processes, together, result in neuroinflammation, degeneration and ultimately neuronal death seen in PD. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP—a prodrug to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+)), rotenone (an environmental neurotoxin), and 6-hydroxydopamine (6-OHDA - a neurotoxic synthetic organic compound) induce PD-like conditions when injected into rodents. All three agents work through similar mechanisms and lead to degeneration of dopaminergic neurons in the substantia nigra (SN) and more recently discovered in motor neurons of the spinal cord (SC). These neurotoxins also increase calpain activity, furthering the neuroinflammatory response. Hence, calpain inhibitors have been posited as potential therapeutics for PD to prevent calpain-related inflammation and neurodegenerative responses in not only the SN but the SC as well.

Abstract: Ferroptosis is an emerging form of non-apoptotic, regulated cell death that is mechanistically dependent on aberrant iron accumulation and excessive lipid peroxidation. Further evidence indicates that ferroptosis plays a crucial role in the efficacy of tumor immunotherapy. Ferroptosis is often constrained by tumor-associated macrophages (TAMs), and this poses a challenge to clinicians aiming to exploit the potency of immunotherapy to treat various forms of cancer. Current advances revealed a dual character to TAMs in regulating tumor ferroptosis. Specifically, some signaling molecules released from cells undergoing ferroptosis can exert effects on TAM polarization. In this review, we summarize the currently characterized mechanisms of macrophage-ferroptosis crosstalk, discuss how macrophage-ferroptosis crosstalk affects the outcome of tumor immunotherapy, and provide an overview of current advances that seek to leverage this crosstalk to improve cancer immunotherapy efficacy. Despite the fact that further efforts are still required to achieve a more comprehensive understanding of the mechanisms that control this signaling, targeting macrophage-ferroptosis crosstalk has clear potential for reversing immunotherapeutic resistance and may shed light on new therapeutic strategies to overcome some advanced and metastatic malignancies.

Abstract: Uveal melanoma (UM) is the most prevalent primary intraocular malignancy in adults with a stable incidence rate between five and seven cases per million in Europe and the United States. Although UM and melanoma from other sites have the same origin, UM has different epidemiological, biological, pathological and clinical features including characteristic metastatic hepatotropism. Despite improvements in the treatment of primary tumours, approximately 50% of patients with UM will develop metastases. In 90% of cases the liver is the first site of metastasis, however the mechanisms underlying this hepatic tropism have not been elucidated. Metastatic disease is associated with a very poor prognosis with a median overall survival of 6 to 12 months. Currently, there is no standard systemic treatment available for metastatic UM and once liver metastases have developed, prognosis is relatively poor. In order to prolong survival, close follow-up in all patients with UM is recommended for early detection and treatment. The treatment of metastatic UM includes systemic chemotherapy, immunotherapy and molecular targeted therapy. Liver-directed therapies, such as resection, radioembolization, chemoembolization, immunoembolization, isolated and percutaneous liver perfusion as well as thermal ablation represent available treatment options. However, to date a consensus regarding the optimal method of treatment is still lacking and the importance of setting guidelines in the treatment and management of metastatic UM is becoming a priority. Improvement in knowledge and a better insight into tumour biology, immunology and metastatic mechanism may improve current treatment methods and lead to the development of new strategies paving the way for a personalized approach.

Abstract: Severe acute respiratory syndrom coronavirus-2 (SARS CoV-2) is the causative agent of coronavirus disease-19 (Covid-19) which has been designated a worldwide pandemic by the World Health Organization on March 11, 2020. Since that time, the virus has mutated and an assortment of variants have been successful at establishing themselves in the human population. This review article describes the SARS CoV-2 genome, hot spot mutations, variants, and then focuses on the Delta variant, finishing up with an update on the Omicron variant. The genome encompasses 11 open reading frames, one of which encodes the spike or S protein that has been the target for vaccines and some of the drugs because of its role in attachment to the human host cell, as well as antibodies. Mutations in the S protein that are common among several of the variants include D614G that increases transmissibility and viral load and is often associated with P323L on the RNA dependent RNA polymerase. N501Y is a mutation in the receptor binding domain of the S protein that increases binding to the ACE-2 receptor on the human host cells by 10 fold. The discussed variants carry combinations of these and other mutations and are classified by the World Health Organization as variants of concern, variants of interest, and variants under monitoring. All variants are characterized by increased transmissibility (relative to the original SARS CoV-2), which is the reason for their ability to establish themselves. Several but not all variants are more resistant to antiviral drugs and less susceptible to antibodies/vaccines. The Delta variant that dominated the world until November 2021 causes an increased risk for hospitalization and death, but is still very susceptible to the current vaccines. The most recent variant, Omicron, is characterized by increased transmissibility and decreased antibody susceptibility.

Abstract: Aluminum, arsenic, cadmium, chromium, cobalt, copper, iron, lead, mercury, nickel, thallium, titanium, zinc, carbon tetrachloride, phthalates, glyphosate, alcohol, drugs, and herbs are under discussion having the potential to injure the human liver, but allocation of the injury to the hepatotoxicant as exact cause is difficult for physicians and requires basic clinical knowledge of toxicology details. Liver injury occurs at a variable extent depending on the dose, mostly reproducible in animal models that allow studies on molecular steps leading to the hepatocellular injury. These exogenous hepatotoxins may cause an overproduction of reactive oxidative species (ROS), which are generated during microsomal or mitochondrial oxidative stress from incomplete oxygen split and trigger the injury if protective antioxidant capacities are reduced. Primary subcelluar target organelles involved are liver mitochondria through lipid peroxidation of membrane structures and the action of free radicals such as singlet radical 1O2, superoxide radical HO•2, hydrogen peroxide H2O2, hydroxyl radical HO•, alkoxyl radical RO•, and peroxyl radical ROO•. They attempt covalent binding to macromolecular structural proteins. As opposed to inorganic chemicals, liver injury due to chemicals with an organic structure proceedes via the hepatic microsomal cytochrome P450 with its different isoforms. In sum, many exogenous chemicals may have the potential of liver injury triggerd by overproduced ROS leading primarily to impairment of mitochondial functions in the course of structural mitochondial membrane dearrangement. As clinical data were often incomplete, future clinical prototols should focus on meeting liver injury criteria, exclusion of alternative causes, a robust causality evaluation management, and obtaining liver histology if clinically indicated and of benefit for the patient.

Abstract: Craniopharyngiomas (CP) are rare noncancerous brain tumors located in the skull base. To date, CP remain challenging-to-resect tumors, owing to their difficult location and invasive potential, with profound adverse effects for the patient if left to grow. Indeed, gross total resection may also be accompanied by unwelcome sequalae, underscoring the need for continued investigation. In the present work, we provide a scoping review of current CP management, with emphasis on our knowledge of their genesis, available treatment options, post-intervention clinical outcomes. Leading theories of CP development are (1) the embryonic theory, explaining the development of adamantinomatous CP from epithelial remnants of Rathke’s pouch and (2) the metaplastic theory, which describes papillary CP development as a result of adenohypophyseal cell metaplasia. Treatment may include surgery, intracystic therapy, or irradiation depending on tumor size, history and location. However, whether a single ideal approach and timing for CP intervention exists remains debated. We appraise and critique these areas with priority for emerging basic results and innovation.

Abstract: BACKGROUND Coronavirus disease-2019 (COVID-19) has become a pandemic around the globe due to the Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2), a new variant of the Coronavirus (CoV) family. The rapid transmission of the infectious disease, 135,646,617 positive cases from which 2,930,732 mortality cases were recorded until 11 April 2021. In an emergency, several existing anti-viral, anti-malarial, and anti-HIV drugs have been used on a repurposing basis. However, without proper clinical evidence, it may create several side effects for the patient. Thus, recommending potential and less-toxic regimens at this emergency stage is the most crucial aspect for any physician. METHODS We have hypothesized a combinatorial drug approach against COVID-19 and to select potential combinations from ten anti-HIV drugs and ten vitamin C derivatives were systematically validated using advanced bioinformatic tools. Initially, the chemical structures used as ligands from PubChem and the target protein, SARS-CoV-2 main protease (PDB ID: 6Y84) from the protein data bank were retrieved for this study. Further, assess the potency, toxicity, drug-ability, and pharmacokinetics profiles using several bioinformatics tools, viz., molecular docking by the AutoDock 4.1 software with predicting activity spectra for substances, Molsoft, ProTox, and SwissADME tools. Molecular dynamics simulation was also employed for most potential candidates to assess their binding stability using GROMACS 5.1.4 software. RESULTS The above computational investigation indicated that 'darunavir with L-ascorbyl-2,6-dibutyrate or ascorbic acid-2-sulfate' combinations strongly inhibit the SARS-CoV-2-main protease as a potential treatment option against COVID-19. Mostly, vitamin C derivatives enhanced the anti-COVID activity and might reduce the post-treatment side effects of darunavir in combination. CONCLUSIONS Overall, the present work suggests that bioinformatics tools are suitable for recognizing potential candidates in an emergency, and herein the selected 'anti-HIV-drug-vitamin c derivatives' cocktails may potential-cum-fewer toxic regimens against COVID-19 treatment.

Abstract: BACKGROUND Atrial fibrillation (AF) is a well-known risk factor for stroke. Predicting the risk is important to prevent the first and secondary attacks of cerebrovascular diseases by determining early treatment. This study aimed to predict the ischemic stroke in AF patients based on the massive and complex Korean National Health Insurance (KNHIS) data through a machine learning approach. METHODS We extracted 65-dimensional features, including demographics, health examination, and medical history information, of 754,949 patients with AF from KNHIS. Logistic regression was used to determine whether the extracted features had a statistically significant association with ischemic stroke occurrence. Then, we constructed the ischemic stroke prediction model using an attention-based deep neural network. The extracted features were used as input, and the occurrence of ischemic stroke after the diagnosis of AF was the output used to train the model. RESULTS We found 48 features significantly associated with ischemic stroke occurrence through regression analysis (p-value < 0.001). When the proposed deep learning model was applied to 150,989 AF patients, it was confirmed that the occurrence ischemic stroke was predicted to be higher AUROC (AUROC = 0.727 ± 0.003) compared to CHA2DS2-VASc score (AUROC = 0.651 ± 0.007) and other machine learning methods. CONCLUSIONS As part of preventive medicine, this study could help AF patients prepare for ischemic stroke prevention based on predicted stoke associated features and risk scores.

Abstract: BACKGROUND Ubiquitination is one of the most common post-translational modifications in cells and dysregulation is closely associated with the development of cancer. However, a comprehensive analysis of the role of ubiquitination in hepatocellular carcinoma (HCC) is still lacking. In this study we analyzed expression and prognostic value of Ubiquitin-Specific Proteases (USPs) in HCC, and the immunological role of USP36 in HCC. METHODS Expression data, prognostic data, and DNA methylation data in cases of HCC were obtained from the cancer genome atlas (TCGA). Overexpression of USP36 in HCC was confirmed in the gene expression omnibus (GEO) database and verified by quantitative PCR in 10 pairs of HCC samples. ULCAN was used to analyze the correlation between USP36 and clinicopathological features. TIMER2.0 and DriverDBv3 were used to analyze the USP36 mutational profile. GSEA analysis explored the potential signaling pathways of USP36 affecting HCC. The immune and stromal scores of HCC samples were calculated using the ESTIMATE algorithm. TIMER1.0 was used to explore the correlation between USP36 and immune cell infiltration. Finally, we analyzed the correlation of USP36 expression with immune checkpoint molecules and determined the IC50 values of 6 chemotherapeutic drugs using the pRRophetic software package. RESULTS Most USPs are abnormally expressed in HCC, among which USP36 and USP39 are most closely associated with HCC prognosis. We also found that USP36 is associated with TP53 mutational status. GSEA analysis indicated that USP36 may affect HCC progression through the dysregulation of various pathways such as ubiquitin-mediated proteolysis. USP36 expression positively correlated with both macrophage infiltration levels and multiple immune checkpoint molecules. Finally, chemosensitivity analysis indicated that chemosensitivity was lower in cells within the USP36 high expression group. CONCLUSIONS Most USPs are abnormally expressed in HCC. Overexpression of USP36 in HCC is closely related to poor prognosis. In particular, the unique immunological role of USP36 may have potential clinical application value.

Abstract: Hashimoto's thyroiditis (HT) is the most common autoimmune disease involving the thyroid gland. HT often clinically manifest as hypothyroidism due to the destruction of thyroid cells mediated by humoral and cellular immunity. The pathogenesis of HT is a complex process in which environmental factors, hereditary inclination, trace elements immune factors, cytokines, and DNA and miRNA all play an important role. Herein, we summarize the precision factors involved in the pathogenesis of HT and offer an update over the past 5 years to provide a theoretical basis for further investigation of the relevant targets for HT treatment.

Abstract: The mitogen-activated protein kinase (MAPK) pathways are ubiquitous in cellular signaling and are essential for proper biological functions. Disruptions in this signaling axis can lead to diseases such as the development of cancer. In this review, we discuss members of the MAP3K family and correlate their mRNA expression levels to patient survival outcomes in different cancers. Furthermore, we highlight the importance of studying the MAP3K family due to their important roles in the larger, overall MAPK pathway, relationships with cancer progression, and the understudied status of these kinases.

Abstract: BACKGROUND Tomato is an important part of daily food, rich source of multitude nutrients, suitable candidate for bio-pharmaceutical production due to berry size and has numerous health benefits. Transcriptional regulation of metalloregulatory heat shock protein-70 family plays pivotal role in plants tolerance against abiotic stress factors including salinity, heat, cold, drought and trace metal elements such as cadmium (Cd2+). METHODS Here, we provide comprehensive report on in-silico identification of SlHsp70 family genes in tomato (Solanum lycopersicum) and their expression in tomato via qPCR analysis under broad range of trace metal elements. RESULTS In-silico analysis revealed 23 SlHsp70 family genes in tomato, phylogenetically divided into four groups I-IV and displayed expression in all tissues. Gene Ontology (GO) analysis revealed that SlHSP70 proteins were membrane localized which were involved in metal ions translocation and oxidoreductase activity to counter hyper-accumlation of reactive oxygen species (ROS). CONCLUSIONS Cd2+ is a widespread heavy metal soil contaminent which is continously polluting fertile soils, a knotty issue which has serious implications over photosynthesis, nitrogen assimilation, minerals and water absorption by plants. Plants exposure to Cd2+ and subsequent qRT-PCR analysis revealed increased expression of SlHsp70-11 in tomato roots, which can be employed in breeding low Cd2+ enriched tomato varieties.

Abstract: BACKGROUND Fetal-placental development depends on a continuous and efficient supply of nutrients from maternal blood that are acquired by exchange through the placenta. However, the placenta is a low permeability barrier, and effective transport of substances depends on specific transport mechanisms. Active transport requires that ions or nutrients be moved against an electrical and/or concentration gradient. In pigs, active transport of ions occurs across the chorioallantois placenta to produce an electrochemical gradient that changes throughout gestation. The aim of this study was to utilize Ussing chambers to detect regulation of ion transport across the porcine chorioallantois by a factor(s) within the uterine-placental environment of pigs. METHODS For the measurement of transchorioallantoic voltage potential as an index of ion transport across the placenta, pieces of chorioallantoic tissue from Day 60 of gestation were mounted into the cassettes of Ussing chambers, and treatments were added to the mucasal side of the tissue. Treatments included: (1) media incubated with Day 60 chorioallantois (placenta-conditioned media); (2) osteopontin/secreted phosphoprotein 1 (OPN/SPP1) purified from cow's milk; (3) placenta-conditioned media from which OPN/SPP1 was removed; and (4) recombinant rat OPN with an intact RGD integrin binding sequence or a mutated RAD sequence. Ouabain was added to both sides of the chamber. Immunofluorescence was utilized to localize beta 3 integrin, aquaporin 8 and OPN/SPP1 in porcine placental tissues, and OPN/SPP1 within porcine lung, kidney and small intestine. RESULTS Day 60 chorioallantoic membranes had greater transepithelial voltage in the presence of porcine placenta-conditioned media, indicating that a molecule(s) released from the placenta increased ion transport across the placenta. OPN/SPP1 purified from cow's milk increased ion transport across the placenta. When OPN/SPP1 was removed from placenta-conditioned media, ion transport across the placenta did not increase. Recombinant rat OPN/SPP1 with a mutated RGD sequence that does not bind integrins (RAD) did not increase ion transport across the placenta. Ouabain, an inhibiter of the sodium-potassium ion pump, ablated ion transport across the placenta. CONCLUSIONS The present study documents a novel pericellular matrix role for OPN/SPP1 to bind integrins and increase ion transport across the porcine chorioallantoic placenta.

Abstract: Malignant melanoma recurrence remains heterogeneous in presentation, ranging from locoregional disease (i.e., local recurrence, satellites, in transit disease) to distant dermal and visceral metastases. This diverse spectrum of disease requires a personalized approach to management and has resulted in the development of both local (e.g., surgery, radiation, intralesional injection) and systemic (intravenous or oral) treatment strategies. Intralesional agents such as oncolytic viruses may also evoke local immune stimulation to induce and enhance the antitumor immune response. Further, it is hypothesized that these oncolytic viruses may convert immunologically “cold” tumors to more reactive “hot” tumor microenvironments and thereby overcome anti-PD-1 therapy resistance. Currently, talimogene laherparepvec (T-VEC), a modified herpes virus, is FDA-approved in this population, with many other oncolytic viruses under investigation in both preclinical and trial settings. Herein, we detail the scientific rationale, current landscape, and future directions of oncolytic viruses in melanoma.

Abstract: The preservation of natural ecosystems, as well as the correct management of human societies, largely depends on the maintenance of critical microbial functions associated with soils. Soils are biodiversity rich pools, and rhizosphere soils can be associated with increased plant functions in addition to the regulation of nutrient cycling, litter decomposition, soil fertility and food production by agriculture systems. The application of biocontrol agents or plant growth-promoting bacteria has been tested in order to colonize roots at initial stages and offer advantages by promoting healthier and higher-yielding crops. In this review we describe the efforts to develop more sustainable systems that seek to minimize environmental disruption while maintaining plant health. Particular emphasis is given in this review to soil improvement strategies and the taxonomic groups involved in plant growth and protection against biotic stresses. It is important to define the impacts of land management and crop production practices on the structure and composition of soil bacterial communities. By promoting, monitoring and controlling the plant microbiome, and understanding the role of certain biocontrol agents within the plant throughout the lifecycle of the plant, we may substantially improve nutritional and environmental standards and reduce the negative impact of some agrochemicals. The integration of biological alternatives with traditional strategies may be critical to improve the sustainability of agriculture systems.

Abstract: Castration-resistant prostate cancer (PCa; CRPC) has a poor response to androgen deprivation therapy and is considered an incurable disease. MicroRNA (miR)-lethal 7c (let-7c) was implied to be a tumor suppressor in PCa, and treatment with exogenous let-7c targets both cancer cells and their associated mesenchymal stem cells (MSCs) to prevent CRPC progression and metastasis. Exosomes are nanometer-sized membrane-bound vesicles which have an absolute predominance in biocompatibility for drug delivery and gene therapy by mediating cell-to-cell communication. By utilizing the intrinsic tumor-targeting property of MSCs, this study aimed to investigate the feasibility of MSC-derived exosomes as an exogenous miR delivery system to target CRPC, using miR let-7c as an example.Bioinformatics analysis was performed to observe miR-let-7c expression in clinical samples by utilizing the GEO database. MSC-derived exosomes were collected from a human bone marrow-derived MSC cell line after cell transfection with either a pre-miR negative control or pre-miR-let-7c, and further characterized through nanoparticle tracking analysis and Western blotting. miR-let-7c expression was determined using RT-qPCR, and the phenotypic effects of both naked and MSC-exosome-encapsulated let-7c on CRPC cells (PC3 and CWR22Rv1) were determined by WST-1 cell proliferation assay and wound healing migration assay.miR-let-7c was downregulated in metastatic PCa and high grade group patients. miR-let-7c expression was confirmed to be downregulated in PCa cell lines, with massively decreased in most metastatic CRPC-like cells. Exogenous miR-let-7c can be successfully packaged into MSC exosomes. Treatment with either naked or MSC-exosome-encapsulated miR-let-7c resulted in significant reductions in cell proliferation and migration in CRPC-like PC3 and CWR22Rv1 cells.MSC-derived exosomes could serve as a therapeutic let-7c delivery system to target CRPC.

Abstract: Cancer has emerged as one of the world's most concerning health problems. The progression and metastasis mechanisms of cancer are complex, including metabolic disorders, oxidative stress, inflammation, apoptosis, and intestinal microflora disorders. These pose significant challenges to our efforts to prevent and treat cancer and its metastasis. Natural drugs have a long history of use in the prevention and treatment of cancer. Many effective anti-tumor drugs, such as Paclitaxel, Vincristine, and Camptothecin, have been widely prescribed for the prevention and treatment of cancer. In recent years, a trend in the field of antitumor drug development has been to screen the active antitumor ingredients from natural drugs and conduct in-depth studies on the mechanisms of their antitumor activity. In this review, high-frequency keywords included in the literature of several common Chinese and English databases were analyzed. The results showed that five Chinese herbal medicines (Radix Salviae, Panax Ginseng C. A. Mey, Hedysarum Multijugum Maxim, Ganoderma, and Curcumaelongae Rhizoma) and three natural compounds (quercetin, luteolin, and kaempferol) were most commonly used for the prevention and treatment of cancer and cancer metastasis. The main mechanisms of action of these active compounds in tumor-related research were summarized. Finally, we found that four natural compounds (dihydrotanshinone, sclareol, isoimperatorin, and girinimbin) have recently attracted the most attention in the field of anti-cancer research. Our findings provide some inspiration for future research on natural compounds against tumors and new insights into the role and mechanisms of natural compounds in the prevention and treatment of cancer and cancer metastasis.

Abstract: BACKGROUND Mesenchymal stem cells (MSCs) are promising candidates for immunomodulatory therapy that are currently being tested in corneal allograft rejection. In this study, we tested the effects of Mesenchymal stem cells derived exosomes in the corneal allograft rejection model. METHODS Mesenchymal stem cells derived exosomes (MSC-exo) were collected and characterized. Wistar-Lewis rat corneal allograft rejection models were established. PKH26 labeled exosomes were used for track experiment. Models were randomly separated into four groups and treated with graded doses of exosomes or same volumn of PBS. Corneal grafts were assessed for rejection degree using slit-lamp biomicroscopy. Grafts were examined histologically using hematoxylin-eosin (H-E) staining and immunohistochemically using antibodies against CD4, CD8 and CD25. A comprehensive graft mRNA gene expression array analysis was conducted and checked by real-time polymerase chain reaction (PCR). RESULTS The nanovesicles obtained were expressing exosome specific protein markers CD9, CD63, CD81. The labeled exosomes could be detected in both cornea and anterior chamber two hours after injection.The 10 μg exosomes subconjunctival injection can effectively prolong graft survival time (MST 16.3 ± 2.5 days). 10 μg exosomes-treated group can inhibit the infiltration of CD4+ and CD25+ T cells. IFN-γ and CXCL11 levels were significantly decreased in grafts obtained from postoperative exosomes-treated rats when compared with controls. CONCLUSIONS MSC-exo can cross biological barrier and play better role directly towards target tissue. MSC-exo can effectively prolong grafts survival time. Th1 signaling pathway was significantly inhibited in the exosomes treated group.

Abstract: BACKGROUND Recently, the incidence of hematological malignancy, such as various leukemias, multiple myeloma and lymphoma, has revealed an increasing tendency, exhibiting a major impact on human health. Most of the available anti-cancer drugs, however, possess high non-targeted accumulation, dosage-associated toxicity, fast elimination, and lack specificity towards tumors, which restrict their utilization in clinical therapy. This extends also to cancer diagnosis where there is a lack of predictive biomarkers. OBJECT Noble metal nanomaterials (NM NMs) have the potential to overcome these shortcomings due to several characteristics including ease of synthesis, ultra-small size, easy surface modification and specific physicochemical properties. At present, gold-, silver- and platinum-based nanomaterials have been employed in the tracing and treatment of hematopoietic tumors through direct individual endocytosis or in innovative drug delivery systems (DDS) by conjugation with other targeting biomolecules. PURPOSE In this mini review, we focus on the use of localized surface plasmon resonance (LSPR)-/surface-enhanced Raman scattering (SERS)- and fluorescence-based diagnosis of NM NMs in the hematological malignancies. Furthermore, the treatment of hematological malignancies utilized the NM NMs or NM NMs-based therapy technology in the chemotherapy, targeted therapy, and photothermal therapy are depicted in depth. The construction of effective and promising NM NMs or NM NMs- dependent theranostic methodology has the potential to provide interdisciplinary knowledge in the development of clinical tracing, diagnosis and treatment of refractory hematological diseases.

Abstract: Utilizing viruses in the treatment of cancer, or oncolytic viral therapy (OVT), began in the 1950s with the idea that viruses could invade and destroy cancer cells. Barriers to this approach included a lack of specificity towards cancer cells and intolerable toxicities. However, it was discovered that OVT increases cytokines such as interferon gamma and interleukins within the tumor microenvironment. This "priming" of the tumor microenvironment can lead to an improved innate immunologic response to tumor cells. An "OVT-as-monotherapy" approach has led to modest tumor response rates that have unfortunately not translated well in clinical trials. Currently, only one OVT agent-talimogene laherparevec (TVEC)-has been approved by the FDA for unresectable melanoma with limited visceral metastases. Further advancements in immunotherapy combined with improved viral engineering over the last decade have paved the way for a renewed focus on OVT. For example, various viruses have been modified to infiltrate and upregulate PD-L1 signaling within tumor cells. Upregulation of PD-L1 on tumor cells can increase tumor cell response to immunotherapies that utilize the interaction between PD-L1 on tumor cells and PD-1 on lymphocytes to allow for immune cell destruction of cancer cells. Combining OVT and immunotherapy offers more promise than OVT as monotherapy. Currently, several are actively investigating the combinatorial approach of OVT and immunotherapy in treating non-small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer, melanoma, pancreatic cancer, multiple myeloma, and head and neck squamous cell carcinoma. In this review, we will discuss the history of OVT including its limitations as a monotherapy. We will also discuss the background of combining OVT and immunotherapy including possible benefits and pitfalls of this approach. Lastly, we will review current clinical trials investigating OVT and immunotherapy in multiple cancers.