GRP78 Downregulation in Keratinocytes Promotes Skin Inflammation through the Recruitment and Activation of CCR6 IL-17A-Producing γδ T Cells.

The migration of γδ T lymphocytes toward skin lesions and their concomitant pathogenic IL-17A production play a crucial role in the pathogenesis of psoriasis. However, the regulatory mechanisms of IL-17A production by γδ T cells and their migration remain to be fully explored. Intracellular GRP78 is a molecular chaperone that regulates endoplasmic reticulum stress, whereas secretory GRP78, as a member of the resolution-associated molecular patterns, exerts immunoregulatory effects.

Secreted glucose regulated protein78 ameliorates DSS-induced mouse colitis.

The secreted form of 78-kDa glucose-regulated protein (sGRP78) has been widely reported for its property in aiding resolution of inflammatory. However, little is known on its potential in the treatment of colitis. To investigate the expression pattern and functional outcome of GRP78 in ulcerative colitis, its expression was measured in human and murine colitis samples.

Chinese expert consensus on intestinal microecology and management of digestive tract complications related to tumor treatment (version 2022).

The human gut microbiota represents a complex ecosystem that is composed of bacteria, fungi, viruses, and archaea. It affects many physiological functions including metabolism, inflammation, and the immune response. The gut microbiota also plays a role in preventing infection.

IL-6 drives T cell death to participate in lymphopenia in COVID-19.

Lymphopenia is a common observation in patients with COVID-19. To explore the cause of T cell lymphopenia in the disease, laboratory results of 64 hospitalized COVID-19 patients were retrospectively analyzed and six patients were randomly selected to trace their changes of T lymphocytes and plasma concentration of IL-6 for the course of disease. Results confirmed that the T-cell lymphopenia, especially CD4 T cell reduction in COVID-19 patients, was a reliable indicator of severity and hospitalization in infected patients.

sGRP78 enhances selective autophagy of monomeric TLR4 to regulate myeloid cell death.

Soluble glucose regulated protein 78 (sGRP78) has long been suggested as a mediator resolution of inflammation. We previously reported that sGRP78 induced the rapid endocytosis of TLR4 with defective TLR4 signaling. To elucidate the underlying mechanisms, in this study, we investigated how sGRP78 influenced the behavior and trafficking of TLR4 in myeloid cells.

Emodin suppresses hepatocellular carcinoma growth by regulating macrophage polarization via microRNA-26a/transforming growth factor beta 1/protein kinase B.

Accumulating evidence has demonstrated that M2 macrophages contribute to the progression of hepatocellular carcinoma (HCC). Emodin is an anti-tumor agent and potentially regulates macrophage polarization. This study aims to explore the effect of emodin on M2 polarization in HCC and its underlying mechanism.

Photosensitizer-loaded gold nanocages for immunogenic phototherapy of aggressive melanoma.

Malignant melanoma remains the life-threatening form of skin cancer with high mortality and poor prognosis. Thus, an ideal melanoma therapeutic strategy is of immediate importance which can remove the primary tumor, as well as inhibit the metastasis and recurrence. Here, we report the fabrication of adjuvant monophosphoryl lipid A (MPLA) lipid bilayer-enveloped and photosensitizer indocyanine green (ICG)-loaded gold nanocages (MLI-AuNCs) for immunogenic phototherapy of aggressive melanoma.

Elevated SARS-Cov-2-Specific IgM Levels Indicate Clinically Unfavorable Outcomes in Patients with COVID-19: A Retrospective Cohort Study.

Background: COVID-19 outbreak began in Wuhan and pandemics occur. Although SARS-CoV-2-specific immunoglobulins have been detected in serum of COVID-19 patients, their dynamics and association with outcomes have not been fully characterized.

Methods: This retrospective cohort study investigated the association between SARS-CoV-2-specific immunoglobulins and clinical outcomes of COVID-19 patients.

Adoptive transfer of GRP78-treated dendritic cells alleviates insulitis in NOD mice.

The 78-kDa glucose-regulated protein (GRP78) has extracellular, anti-inflammatory properties that can aid resolving inflammation. It has been established previously that GRP78 induced myeloid CD11c cell differentiation into distinct tolerogenic cells. This tolerance induction makes GRP78 a potential therapeutic agent for transplanted allogeneic grafts and autoimmune diseases, such as type 1 diabetes.

Multifunctional CuS- and DOX-loaded AuNR@mSiO platform for combined melanoma therapy with inspired antitumor immunity.

Combined antitumor therapies based on nanomedicines have shown efficacy in various tumor models in recent years, overcoming the disadvantages of inefficiency and undesired toxicity of traditional therapies. Herein, we present a copper sulfide- and doxorubicin-loaded gold nanorods@mesoporous SiO2 multifunctional nanocomposite (AuNR@mSiO2@DOX-CuxS-PEG) to integrate chemotherapy, the photothermal properties of AuNRs, and the photodynamic properties of CuxS into a single nanoplatform based on hydrophobic interaction and electrostatic attraction. Upon near-infrared light irradiation, the AuNR@mSiO2@DOX-CuxS-PEG nanocomposites exhibit a synergistic therapeutic effect and inhibit the in situ tumor growth and lung metastasis in a melanoma model.

The Transferrin Receptor-Directed CAR for the Therapy of Hematologic Malignancies.

As many patients ultimately relapse after chimeric antigen receptor (CAR) T-cell therapy, identification of alternative targets is currently being evaluated. Substantial research efforts are underway to develop new targets. The transferrin receptor (TfR) is prevalently expressed on rapidly proliferating tumor cells and holds the potential to be the alternative target.

Transcriptomic characterization reveals prognostic molecular signatures of sorafenib resistance in hepatocellular carcinoma.

Sorafenib is the first-line treatment for patients with advanced unresectable hepatocellular carcinoma (HCC); however, only a small number of patients benefit from sorafenib, and many develop sorafenib resistance (SR) and severe side effects. To identify biomarkers for SR, we systematically analyzed the molecular alterations in both sorafenib-resistant HCC specimens and cultured cells. By combining bioinformatics tools and experimental validation, four genes (, insulin-like growth factor 2 receptor, complement factor B, and paraoxonase 1) were identified as key genes related to SR in HCC and as independent prognostic factors significantly associated with clinical cancer stages and pathological tumor grades of liver cancer.

[Corrigendum] Mutation of TGF‑β receptor II facilitates human bladder cancer progression through altered TGF‑β1 signaling pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, in Fig. 1B on p. 1552, the MCF‑7 and T24, and the A549 and ScaBER data panels, respectively, appeared to be strikingly similar.

Persistence of SARS-CoV-2-specific antibodies in COVID-19 patients.

To better understand humoral immunity following SARS-CoV-2 infection, 114 hospitalised COVID-19 patients with antibody monitored over 8 weeks from symptom onset were retrospectively investigated. A total of 445 serum samples were assessed via chemiluminescence immunoassay. Positive rate of virus-specific IgM reached up to over 80% from the second week to the eighth week after symptom onset, then declined quickly to below 30% in the twelfth week.

Tumor-Secreted GRP78 Promotes the Establishment of a Pre-metastatic Niche in the Liver Microenvironment.

The liver is an immunologically tolerant organ and a common site of distant metastasis for various cancers. The expression levels of glucose-regulated protein 78 (GRP78) have been associated with tumor malignancy. Secretory GRP78 (sGRP78) released from tumor cells contributes to the establishment of an immunosuppressive tumor microenvironment by regulating cytokine production in macrophages and dendritic cells (DCs).

ZnO-based multifunctional nanocomposites to inhibit progression and metastasis of melanoma by eliciting antitumor immunity via immunogenic cell death.

The development of a highly effective and tumor-specific therapeutic strategy, which can act against the primary tumor and also condition the host immune system to eliminate distant tumors, remains a clinical challenge. Herein, we demonstrate a facile yet versatile ZnO-capping and Doxorubicin (DOX)-loaded multifunctional nanocomposite (AuNP@mSiO@DOX-ZnO) that integrates photothermal properties of gold nanoparticles (NPs), pH-responsive properties and preferential selectivity to tumor cells of ZnO QDs and chemotherapeutic agent into a single NP. The photothermal performance, pH-triggered release and preferential phagocytic ability were assessed.

Efficacy and safety of continuous antiviral therapy from preconception to prevent perinatal transmission of hepatitis B virus.

Few studies were conducted to assess safety and efficacy of continuous antiviral therapy administrated from preconception. In the present study, 136 eligible women with chronic HBV infection were recruited, and assigned to active chronic hepatitis B (CHB) (Group A, B or C) or chronic HBV carrier (Group D). Antiviral therapy was administrated in preconception (Group A), in early (Group B) or late pregnancy (Group C and Group D).

HBV infection exacerbates PTEN defects in hepatocellular carcinoma through upregulation of miR-181a/382/362/19a.

A high hepatitis B virus (HBV) load and chronic hepatitis B infection are well-recognized risk factors for the development of hepatocellular carcinoma (HCC), highlighting the need for research into the mechanisms underlying the role of HBV infection in HCC. Because phosphatase and tensin homolog (PTEN) has been implicated in HCC development, we explored whether PTEN has a role in HBV-related hepatocarcinogenesis. We found that PTEN expression was correlated with advanced clinicopathological features and that HBV infection exacerbates PTEN defects in HCC.

Integrated Bioinformatics Analysis Identifies ELAVL1 and APP as Candidate Crucial Genes for Crohn's Disease.

Immune imbalance and barrier destruction of intestinal mucosa are the central pathogenic factors of Crohn's disease (CD). In this study, three independent microarray studies of CD were integrated and 9912 differentially expressed genes (DEGs) were analysed by NetworkAnalyst to screen candidate crucial genes. NetworkAnalyst identified ELAV-like RNA binding protein 1 (ELAVL1) as the most crucial upregulated gene and amyloid- precursor protein (APP) as the most crucial downregulated gene in peripheral blood of CD patients.

Establishment of a hTfR mAb-functionalized HPPS theranostic nanoplatform.

: Many efforts have been made to develop ligand-directed nanotheranostics in cancer management which could afford both therapeutic and diagnostic functions as well as tumor-tailored targeting. Theranostic nanoplatform targeting transferrin receptor (TfR) is an effective system for favorable delivery of diagnostic and therapeutic agents to malignancy site. : To enable amalgamation of therapy and diagnosis to many TfR tumor, hTfR (human TfR) monoclonal antibody (mAb)-functionalized HPPS nanoparticle (HPPS-mAb) was prepared with hTfR mAb on the shell and with fluorophore DiR-BOA in the core.

Prostate cancer awareness and screening practice among Kenyan men.

Despite globally increased awareness and widespread availability of screening tools, little is known about prostate cancer (PCa) awareness and screening practices in Kenya. To assess PCa awareness and screening practice among Kenyan men (age: 15-54 years), a cross-sectional study was carried out using Kenya Demographic Health Survey (KDHS 2014) data. A subsample of 12 803 men was taken and analyzed using SPSS version 22.

Selection for Anti-transferrin Receptor Bispecific T-cell Engager in Different Molecular Formats.

Selecting an ideal molecular format from diverse structures is a major challenge in developing a bispecific antibody (BsAb). To choose an ideal format of anti-CD3 × anti-transferrin receptor (TfR) bispecific antibodies for clinical application, we constructed TfR bispecific T-cell engager (BiTE) in two extensively applied formats, including single-chain tandem single-chain variable fragments (scFvs) and double-chain diabodies, and evaluated their functional characterizations in vitro. Results demonstrated that TfR-BiTE in both formats directed potent killing of TfR HepG2 cells.

Factors affecting HIV counselling and testing among Ethiopian women aged 15-49.

Background: HIV voluntary counseling and testing (VCT) is a crucial gateway to all strategies related to care, prevention and treatment of human immunodeficiency virus (HIV) infection. Nevertheless, utilization of voluntary counselling and testing (VCT) service among adults is very low in Ethiopia. The objective of this study is to identify determinants associated with VCT utilization among adult women aged 15-49 in Ethiopia.

Polyethylenimine Hybrid Thin-Shell Hollow Mesoporous Silica Nanoparticles as Vaccine Self-Adjuvants for Cancer Immunotherapy.

Conventional adjuvants (e.g., aluminum) are insufficient to trigger cell-mediated immunity, which plays a crucial role in triggering specific immunity against cancer.

LINC01149 variant modulates MICA expression that facilitates hepatitis B virus spontaneous recovery but increases hepatocellular carcinoma risk.

Interpreting disease-causing variants, especially in noncoding regions by genome-wide association studies (GWAS), has become one of the most challenging and demanding tasks. We hypothesized that functional lncRNAs variants in GWAS-identified loci might alter expression level of genes associated with persistent HBV infection and hepatocellular carcinoma (HCC). Integrated bioinformatics approaches were used to prioritize potentially functional variants and a two-stage case-control study (2473 HBV positive HCC patients, 2248 persistent HBV carriers and 2294 spontaneously recovered subjects) was performed to assess the roles of these variants.