Tuberous Sclerosis Complex With Multiple Organ Tumors: Case Report and Literature Review

Pancreatic neuroendocrine neoplasms (PNEN) are tumors that originate from neuroendocrine cells. Only about 1% patients are related to mutation of tuberous sclerosis complex gene. Here, we reported a rare case with involvement of multiple organs and space-occupying lesions. Initially, the patient was thought to have metastasis of a pancreatic tumor. However, the patient was diagnosed as pancreatic neuroendocrine tumors, liver perivascular epithelioid tumors, splenic hamartoma, and renal angiomyolipoma by pathological examination after surgery. We performed genetic mutation detection to identify that tuberous sclerosis complex 2 gene presented with a heterozygous variant. Tuberous sclerosis often presents with widespread tumors, but it is less common to present with pancreatic neuroendocrine tumors and liver perivascular tumors as highlighted in the case. So we analyzed the relationship between TSC gene mutations and related tumors. And we also reviewed the current molecular mechanisms and treatments for tuberous sclerosis complex

Ulcerative colitis complicated by primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome: a case report and literature review

Primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and ulcerative colitis (UC) are immune diseases of the digestive system. Some patients develop overlap syndrome, the presentation of two or more of the clinical, biochemical, immunological, and histological features of these conditions simultaneously or sequentially. The incidence of UC in PSC-AIH overlap syndrome is as high as 50%. In contrast, PSC-AIH overlap syndrome is rare in UC patients. However, because it has a low prevalence and has been studied in less detail, PSC is often misdiagnosed as primary biliary cholangitis (PBC) in its early stage. Herein, we reported a case of a 38-year-old male patient who presented to a clinician in 2014 with irregular bowel habits. A colonoscopy suggested UC. In 2016, the patient was found to have abnormal liver function and was diagnosed with PBC by pathology. He was treated with ursodeoxycholic acid (UDCA) but this had no effect on his liver function. Additional liver biopsies in 2018 indicated PBC-AIH overlap syndrome. The patient refused hormone therapy for personal reasons. Following UDCA monotherapy, his liver function remained abnormal. The patient was reexamined after repeated abnormal liver function tests and bowel symptoms. Systematic laboratory testing, imaging diagnosis, colonoscopy, liver biopsy, and various pathological examinations conducted in 2021 were used to diagnose the patient with PSC-AIH-UC overlap syndrome. He was treated with various drugs, including UDCA, methylprednisolone, mycophenolate mofetil, and mesalazine. His liver function improved significantly after treatment and follow-up is ongoing. Our case report highlights the need to raise awareness about rare and difficult-to-diagnose clinical disorders

TRIM55 inhibits colorectal cancer development via enhancing protein degradation of c‐Myc

Abstract Background Colorectal cancer (CRC) is one of the most common and lethal malignancies which including colon and rectum cancer. Tripartite motif containing 55 (TRIM55) is an E3 ubiquitin ligase belonging to the TRIM family. Although the aberrant TRIM55 expression has been implicated in several tumors, its functional role, and molecular mechanisms in CRC remain unknown. Methods Immunohistochemical studies, qRT‐PCR, and Western blot were performed to analyze the expression of TRIM55 in CRC patients and cell lines. TRIM55 expression and its relevance to clinical traits and prognosis were further explored in the TCGA database, and in our 87 clinical samples. Subsequently, we performed a series of functional assays to explore the effect of TRIM55 on CRC progression. Finally, the molecular mechanism of TRIM55 was investigated by immunoprecipitation and ubiquitination analyses. Results Here, we demonstrated that TRIM55 was markedly downregulated in CRC cell lines and tumors from CRC patients. Moreover, overexpression of TRIM55 could suppress CRC cell growth in vitro and inhibit CRC xenograft tumor development in vivo. Additionally, TRIM55 overexpression dampened CRC cell migration and invasion. Further bioinformatics analysis indicated that TRIM55 suppressed cyclin D1 and c‐Myc expression. Mechanistically, co‐immunoprecipitation assay revealed that TRIM55 directly interacted with c‐Myc and down‐regulated its protein expression level via protein ubiquitination. Intriguingly, c‐Myc overexpression partially antagonized the function of TRIM55 overexpression. Conclusions Taken together, our findings suggest that TRIM55 inhibits CRC tumor development via, at least in part, enhancing protein degradation of c‐Myc. Targeting TRIM55 could provide a new therapeutic approach for CRC patients

Blends of hydrophobic and swelling agents in the swelling layer in the preparation of delayed-release pellets of a hydrophilic drug with low MW: Physicochemical characterizations and in-vivo evaluations

In this study, a hydrophobic material, ethylcellulose, which was used as its aqueous suspension Surelease®, was combined with a swelling agent as the swelling layer to prepare delayed-release pellets for Danshensu, which is a hydrophilic drug with low MW. A rupturable, delayed-release pellet consists of a drug core, a swelling layer containing a swelling agent (cross-linked sodium carboxymethyl cellulose) with a hydrophobic agent (Surelease®), and a controlled layer composed by an insoluble, water-permeable polymeric coating (aqueous ethylcellulose dispersions) was developed in a fluidised bed. Results showed that blending Surelease® into the swelling layer could effectively extend the release of Danshensu from the pellets, which may be attributed to the slowed swelling rate by reduction of water penetration and improvement of mechanical integrity of the swelling layer. Drug in the delayed pellets showed sustained release in beagle dogs after oral administration with comparable in-vivo exposure to the uncoated drug pellets. In conclusion, blends of hydrophobic and swelling agents in the swelling layer in double-membrane pellets could achieve a delayed drug-release profile in vitro, as well as delayed and sustained absorption in vivo for highly soluble, low-MW drug. The present study highlighted the potential use of a delayed-release system for other hydrophilic, low-MW drugs to meet the formulation requirements for chronopharmacological diseases

Immunotoxicity assessment of CdSe/ZnS quantum dots in macrophages, lymphocytes and BALB/c mice

Background: The toxicity of CdSe/ZnS quantum dots (QDs) in the environment and biological systems has become a major concern for the nanoparticle community. However, the potential toxicity of QDs on immune cells and its corresponding immune functions remains poorly understood. In this study, we investigated the immunotoxicity of CdSe/ZnS QDs using the in vitro in macrophages and lymphocytes and in vivo in BALB/c mice. Results: Our results indicated that macrophages treated with 1.25 or 2.5 nM QDs exhibited decreased cell viability, increased levels of reactive oxygen species (ROS), elevated apoptotic events, altered phagocytic ability, and decreased release of TNF-α and IL-6 by upon subsequent stimulation with Lipopolysaccharide (LPS). In contrast, lymphocytes exposed to QDs exhibited enhanced cell viability, increased release of TNF-α and IL-6 following exposure with CpG-ODN, and decreased transformation ability treatment in response to LPS. To study the in vivo effects in mice, we showed that QDs injection did not cause significant changes to body weight, hematology, organ histology, and phagocytic function of peritoneal macrophages in QDs-treated mice. In addition, the QDs formulation accumulated in major immune organs for more than 42 days. Lymphocytes from QDs-treated mice showed reduced cell viability, changed subtype proportions, increased TNF-α and IL-6 release, and reduced transformation ability in response to LPS. Conclusions: Taken together, these results suggested that exposures to CdSe/ZnS QDs could suppress immune-defense against foreign stimuli, which in turn could result in increased susceptibility of hosts to diseases.ASTAR (Agency for Sci., Tech. and Research, S’pore)Published versio

Glycyrrhizic Acid Attenuates Pulmonary Fibrosis of Silicosis by Inhibiting the Interaction between HMGB1 and BRG1 through PI3K/Akt/mTOR Pathway

Purpose: High mobility group protein 1 (HMGB1) is a highly conserved DNA-binding nuclear protein that participates in the occurrence and development of silicosis. HMGB1 binds to its specific receptor and activates phosphatidylinositol 3-kinase (PI3K)/protein kinase B, (PKB; Akt)/mammalian target of rapamycin (mTOR) pathway. Brahma-related genes 1 (BRG1; SMARCA4) is the core subunit of SWI/SNF. HMGB1 activates the Akt pathway through BRG1 to promote the proliferation of prostate cancer. Glycyrrhizic acid is a new pharmacological inhibitor of HMGB1, which may inhibit the occurrence and development of silicosis. We speculate that glycyrrhizic acid inhibits the interaction between HMGB1 and BRG1 through the PI3K/Akt/mTOR pathway to affect the progression of silicosis. Methods: We carried out an in vitro study and stimulated A549 with TGF-β1 to establish an epithelial–mesenchymal transition (EMT) model, knocked down the HMGB1 and BRG1 genes in cells, observed the expression of EMT markers, and detected the interaction between HMGB1 and BRG1 by co-immunoprecipitation. In vivo, we injected glycyrrhizic acid into the mouse silicosis model to inhibit the expression of HMGB1. Results: Both HMGB1 and BRG1 were highly expressed in the process of EMT. After knocking down HMGB1 and BRG1, the process of EMT was inhibited through the PI3K/Akt/mTOR pathway, and their expressions were influenced by each other. HMGB1 and BRG1 interact with each other in A549 cells. HMGB1 and BRG1 are also highly expressed in the mouse silicosis model, and glycyrrhizic acid can inhibit the expression of HMGB1/BRG1 through the PI3K/Akt/mTOR pathway. Conclusion: Glycyrrhizic acid can inhibit the interaction between HMGB1 and BRG1 through the PI3K/Akt/mTOR pathway to affect the progression of silicosis

Enantioselective Fluorescent Recognition in the Fluorous Phase: Enhanced Reactivity and Expanded Chiral Recognition

A novel perfluoroalkyl-BINOL-based chiral diketone is found to be the first highly enantioselective fluorescent sensor in the fluorous phase. One enantiomer of a chiral amino alcohol or diamine at a concentration greater than 1 mM can cause an up to 1200–2000-fold fluorescent enhancement of the sensor (0.08 mM), while the other enantiomer gives only a 10–50-fold enhancement. The fluorous-phase-based sensor is found to enhance the reactivity of the previously reported fluorous insoluble sensor with amino alcohols and expand its chiral recognition ability. Dynamic light scattering studies show the formation of aggregates of very different particle sizes when two enantiomers of a substrate interact with the sensor in perfluorohexane (FC-12). This substantial difference enables easy discrimination of the enantiomers with UV-lamps or even the naked eye. NMR, IR, and mass spectroscopic studies indicate that the fluorescent enhancement and enantioselectivity should originate from the fluorous solvent-promoted nucleophilic addition of the amino alcohols to the carbonyl groups of the sensor

MOESM1 of Immunotoxicity assessment of CdSe/ZnS quantum dots in macrophages, lymphocytes and BALB/c mice

Additional file 1. Results from flow cytometry analysis of QDs uptake, ICP-MS analysis of Se element in major organs, the phagocytic assay of peritoneal macrophages, and MTT assay of macrophages treated with different types of QDs are presented

Towards bioresource-based aggregation-induced emission luminogens from lignin β-O-4 motifs as renewable resources

Abstract One-pot synthesis of heterocyclic aromatics with good optical properties from phenolic β-O-4 lignin segments is of high importance to meet high value added biorefinery demands. However, executing this process remains a huge challenge due to the incompatible reaction conditions of the depolymerization of lignin β-O-4 segments containing γ-OH functionalities and bioresource-based aggregation-induced emission luminogens (BioAIEgens) formation with the desired properties. In this work, benzannulation reactions starting from lignin β-O-4 moieties with 3-alkenylated indoles catalyzed by vanadium-based complexes have been successfully developed, affording a wide range of functionalized carbazoles with up to 92% yield. Experiments and density functional theory calculations suggest that the reaction pathway involves the selective cleavage of double C-O bonds/Diels-Alder cycloaddition/dehydrogenative aromatization. Photophysical investigations show that these carbazole products represent a class of BioAIEgens with twisted intramolecular charge transfer. Distinctions of emission behavior were revealed based on unique acceptor-donor-acceptor-type molecular conformations as well as molecular packings. This work features lignin β-O-4 motifs with γ-OH functionalities as renewable substrates, without the need to apply external oxidant/reductant systems. Here, we show a concise and sustainable route to functional carbazoles with AIE properties, building a bridge between lignin and BioAIE materials