Toxic Epidermal Necrolysis and Stevens - Johnson Syndrome Following Sintilimab Administration in a Non-Small Cell Lung Cancer Patient: A Case Report.

Immune checkpoint inhibitors such as monoclonal antibodies have been used recently with greater effect for the management of non-small cell lung cancer (NSCLC). Sintilimab, a fully human IgG4 monoclonal antibody is specific for the immune checkpoint protein programmed cell death receptor-1 (PD-1). It is a common medication adopted for treating Hodgkin's lymphoma and NSCLC. The adverse effects associated with the use of monoclonal antibodies should be closely monitored and in the current report, the use of sintilimab for treating NSCLC led to skin-associated adverse effects such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Genetic testing showed that genes such as KRAS, CREBBP, NTRK1, RAF1, and TP53 were mutated. Initial visible symptom included the formation of a vesicular rash on the skin that had spread to the upper limbs, chest, and dorsum 1 week after the administration of sintilimab. The patient received anti-inflammatory agents to prevent worsening of the rashes and further infections. When the vesicles in back and limbs enlarged and the neck skin began to desquamate, the patient was diagnosed with Stevens-Johnson syndrome and sintilimab-induced toxic epidermal necrolysis. Toxic epidermal necrolysis was diagnosed via clinical symptoms and physical examination. The patient also reported the symptoms of oral mucositis. As soon as the dose of sintilimab was reduced to 20 mg/day, the skin-associated condition of the patient began to improve. Although the lump in the lungs decreased considerably 45 days after initial administration of sintilimab, the medication was stopped from use as soon as the skin-related symptoms improved after its withdrawal. This report suggests that close monitoring, personal care, and proper use of medications such as sintilimab should be implemented to avoid such rare skin-associated toxicities as an adverse effect.

Functional Separator Enabled by Covalent Organic Frameworks for High-Performance Li Metal Batteries.

Uncontrolled ion transport and susceptible SEI films are the key factors that induce lithium dendrite growth, which hinders the development of lithium metal batteries (LMBs). Herein, a TpPa-2SO3 H covalent organic framework (COF) nanosheet adhered cellulose nanofibers (CNF) on the polypropylene separator (COF@PP) is successfully designed as a battery separator to respond to the aforementioned issues. The COF@PP displays dual-functional characteristics with the aligned nanochannels and abundant functional groups of COFs, which can simultaneously modulate ion transport and SEI film components to build robust lithium metal anodes. The Li//COF@PP//Li symmetric cell exhibits stable cycling over 800 h with low ion diffusion activation energy and fast lithium ion transport kinetics, which effectively suppresses the dendrite growth and improves the stability of Li+ plating/stripping. Moreover, The LiFePO4//Li cells with COF@PP separator deliver a high discharge capacity of 109.6 mAh g-1 even at a high current density of 3 C. And it exhibits excellent cycle stability and high capacity retention due to the robust LiF-rich SEI film induced by COFs. This COFs-based dual-functional separator promotes the practical application of lithium metal batteries.

Roles of anoikis in colorectal cancer therapy and the assessment of anoikis-regulatory molecules as therapeutic targets.

Colorectal cancer (CRC) is a deadly malignancy and therapeutic approaches for CRC are evolving every day. Anoikis is a key mechanism for programmed cell death of cancer cells that undergo anchorage-independent growth at a different matrix than the one which is expected. Yet, anoikis is a less studied mechanism of cell death in comparison to other mechanisms such as apoptosis. Relating to this, resistance to anoikis among cancer cells remains critical for improved metastasis and survival in a new environment evading anoikis. Since CRC cells have the ability to metastasize from proximal sites to secondary organs such as liver and promote cancer in those distant sites, a clear knowledge of the mechanisms essential for anchorage-independent growth and subsequent metastasis is necessary to counteract CRC progression and spread. Therefore, the identification of novel drug candidates and studying the roles of anoikis in assisting CRC therapy using such drugs can prevent anchorage-independent cancer cell growth. Additionally, the identification of novel biomarkers or therapeutic targets seems essential for implementing superior therapy, impeding relapse among malignant cells and improving the survival rate of clinical patients. As there are no reviews published on this topic till date, anoikis as a mechanism of cell death and its therapeutic roles in CRC are discussed in this review. In addition, several molecules were identified as therapeutic targets for CRC.

Human gut-microbiome interplay: Analysis of clinical studies for the emerging roles of diagnostic microbiology in inflammation, oncogenesis and cancer management.

Microorganisms have been known to coexist in various parts of human body including the gut. The interactions between microbes and the surrounding tissues of the host are critical for fine fettle of the gut. The incidence of such microorganisms tends to vary among specific type of cancer affected individuals. Such microbial communities of specific tumor sites in cancer affected individuals could plausibly be used as prognostic and/or diagnostic markers for tumors associated with that specific site. Microorganisms of intestinal and non-intestinal origins including Helicobacter pylori can target several organs, act as carcinogens and promote cancer. It is interesting to note that diets causing inflammation can also increase the cancer risk. Yet, dietary supplementation with prebiotics and probiotics can reduce the incidence of cancer. Therefore, both diet and microbial community of the gut have dual roles of prevention and oncogenesis. Hence, this review intends to summarize certain important details related to gut microbiome and cancer.

Synthesis, optimization and characterization of silver nanoparticles using the catkin extract of Piper longum for bactericidal effect against food-borne pathogens via conventional and mathematical approaches.

Inspired with an increasing environmental awareness, we performed an eco-friendly amenable process for the synthesis of silver nanoparticles (AgNPs) using the catkins of Piper longum as an alternative approach with the existing methods of using plant extracts. The fabrication of nanoparticles occurred within 10 min. This was initially observed by colour change of the solution. UV-visible spectroscopic studies (UV-Vis) were performed for further confirmation. The analysis elucidated that the surface plasmon resonance (SPR) was specifically corresponding to AgNPs. Fourier transform infrared spectrophotometry (FTIR) studies indicated that polyphenols could possibly be the encapsulating agents. The size and shape of the nanoparticles was analysed using Transmission electron microscopy (TEM). The nanoparticles were predominant spheres ranging between 10 and 42 nm at two different scales. The formation of elemental silver was confirmed further by X-ray photoelectron spectroscopy (XPS) and X-ray powder diffraction (XRD). GC-MS analysis was used to identify the possible encapsulates on the nanoparticles. The antibacterial effect of the biosynthesized AgNPs was tested against two gram-positive (Bacillus cereus and Staphylococcus aureus), and five gram-negative (Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella typhi) bacteria. Outcomes of the study suggest that these pathogens were susceptible to the AgNPs. This is the first ever international report on correlating the antibacterial effect of silver nanoparticles using mathematical modelling with a conventional antimicrobial assay. The results indicate that nanoparticles of silver synthesized using catkin extract of P. longum can be exploited towards the development of potential antibacterial agents.

MiR-384 inhibits proliferation and migration of trophoblast cells via targeting PTBP3.

Preeclampsia (PE) is one type of hypertension during pregnancy that seriously threatens maternal and infant health. Trophoblast dysfunction, such as decreased proliferation and migration, is closely related to the occurrence and development of PE. MicroRNAs (miRNAs) have been proven to play an important role in many diseases, including PE. miR-384 was reported to play a regulatory role in promoting cell apoptosis and inhibiting proliferation, migration and invasion in a variety of tumors. Previously, we found that miR-384 is upregulated in the placenta and plasma in the context of PE. In this study, we elucidated the function of miR-384 in the trophoblast cell line HTR-8/SVneo and the trophoblastic tumor cell line JEG-3. Cell proliferation and migration were inhibited by miR-384 overexpression but promoted by miR-384 downregulation. Subsequently, polypyrimidine tract-binding protein 3(PTBP3) was found to be a direct target gene of miR-384. PTBP3 was downregulated in placental tissues from PE patients, and a negative correlation was found between PTBP3 and miR-384. Our results suggest that the miR-384/PTBP3 axis plays an important role in regulating trophoblast function during the progression of PE, and these data provide novel insight into the molecular pathogenesis of this disorder.

ß-elemene regulates endoplasmic reticulum stress to induce the apoptosis of NSCLC cells through PERK/IRE1α/ATF6 pathway.

Endoplasmic reticulum stress (ERs) has been regarded as an important cause for the pathogenesis of non-small-cell lung cancer (NSCLC). ß-elemene is an active component in the essential oil extracted from a medicinal herb, Curcuma wenyujin, and has been reported to be effective against non-small-cell lung cancer (NSCLC). However, the potential effect and underlying mechanisms of ß-elemene on regulating ERs to inhibit NSCLC are still unclear. In the present study, A549 cells and Lewis tumor-bearing C57BL/6J mice were established to evaluate this effect. Visualsonics Vevo 2100 Small Animal Dedicated High-frequency Color Ultrasound was performed to observe tumor volume in vivo. 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) was used to evaluate cell vitality of A549 cells. Furthermore, western blotting (WB), immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (q-PCR) were applied to detect the ERs-related proteins. Flow cytometry was also applied to detect cell apoptosis and assay kit for reactive oxygen species (ROS) generation. Our results showed that ß-elemene inhibited lung cancer tumor growth and cell vitality in a dose- and time-dependent manner. Not only that, ß-elemene could up-regulate ERs-related proteins like PERK, IRE1α, ATF6, ATF4, CHOP and down-regulate the Bcl-2 expression. More importantly, ERs inhibitor 4-PBA, IRE1α inhibitor STF-083010, ATF6 inhibitor Anti-ATF6 and PERK inhibitor GSK2656157 can all reduce the amplitude of protein expression changes and apoptosis rates, then weaken the anti-tumor effect of ß-elemene. Therefore, the present in vivo and in vitro study revealed that the anti-NSCLC effect of ß-elemene is closely related to the activation of ERs through PERK/IRE1α/ATF6 pathway, and this might be beneficial for clinical therapy of NSCLC.