Thrombopoietin improves the functions of bone marrow endothelial progenitor cells via METTL16/Akt signalling of haematological patients with chemotherapy-induced thrombocytopenia.

Bone marrow endothelial progenitor cells (BM EPCs) are crucial in supporting haematopoietic regeneration, while the BM EPCs of haematological patients with chemotherapy-induced thrombocytopenia (CIT) are unavoidably damaged. Therefore, the present study aimed to examine the effect of thrombopoietin (TPO) on the recovery of BM EPCs of CIT patients and to identify the underlying mechanisms. The cell functions were determined by 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil)-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake and fluorescein isothiocyanate (FITC)-labeled Ulex europaeus agglutinin-I (FITC-UEA-I) binding assay, as well as proliferation, migration and tube formation experiments. Endothelial cells were transfected with METTL16 lentivirus, followed by methylated RNA immunoprecipitation sequencing. Zebrafish with vascular defect was used as the in vivo model. TPO significantly improved the quantity and functions of BM EPCs from CIT patients in vitro and restored the subintestinal vein area of zebrafish with vascular defect in vivo. Mechanically, TPO enhanced the BM EPC functions through Akt signal mediated by METTL16, which was downregulated in BM EPCs of CIT patients and involved in the regulation of endothelial functions. The present study demonstrates that TPO improves the recovery of BM EPCs from CIT patients with haematological malignancies via METTL16/Akt signalling, which provides new insights into the role of TPO in treating CIT in addition to direct megakaryopoiesis.

Oncological characteristics, treatments and prognostic outcomes in MMR-deficient colorectal cancer.

Colorectal cancer (CRC) ranks as the third most prevalent cancer globally. It's recognized that the molecular subtype of CRC, characterized by mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H), plays a critical role in determining appropriate treatment strategies. This review examines the current molecular classifications, focusing on dMMR/MSI-H CRC and its subtypes: Lynch syndrome (LS), Lynch-like syndrome (LLS), and sporadic cases. Despite advances in understanding of these genetic backgrounds, clinical trials have not conclusively differentiated the efficacy of immune checkpoint inhibitors among these subgroups. Therefore, while this review details the molecular characteristics and their general implications for treatment and prognosis, it also highlights the limitations and the need for more refined clinical studies to ascertain tailored therapeutic strategies for each subtype. Furthermore, this review summarizes completed and ongoing clinical studies, emphasizing the importance of developing treatments aligned more closely with molecular profiles. By discussing these aspects, the review seeks to provide a comprehensive analysis of oncological characteristics, presenting a detailed understanding of their implications for treatment and prognosis in dMMR/MSI-H CRC.

Non-Hodgkin's lymphoma involving chronic difficult-to-heal wounds: A case report.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) is a malignant tumor that originates from the lymphoid tissues and can potentially affect numerous organs within the body. Among these, the skin stands out as one of the primary sites affected by NHL, often presenting with multiple extra-nodal manifestations. In this report, we present an unusual case of NHL involving chronic wounds in the lower extremities that were difficult to heal. The scars were successfully treated using radiotherapy in combination with extended excision debridement and peroneal artery perforator flap grafting, resulting in satisfactory outcomes. CASE SUMMARY: A 19-year-old male patient presented with ulceration of the skin on the left calf near the ankle accompanied by purulent discharge. Subsequent pathologic biopsy confirmed a diagnosis of NHL (extranodal NK/T-cell lymphoma, nasal type). Initial treatment comprised local radiotherapy and wound care; however, the wound exhibited prolonged non-healing. Consequently, the patient underwent a series of interventions including radiotherapy, wound enlargement excision debridement, and peroneal artery perforator flap grafting. Ultimately, successful healing was achieved with favorable postoperative outcomes characterized by good texture of the flap without any signs of rupture or infection. CONCLUSION: The combination of radiotherapy, wound enlargement excision debridement, and peroneal artery perforator flap grafting may present a favorable treatment modality for chronic non-healing lower leg wounds resulting from NHL.

Inhibition of human UDP-glucuronosyltransferase enzyme by entrectinib: Implications for drug-drug interactions.

As a new type of oral tyrosine kinase inhibitor, entrectinib can act on multiple targets and exert efficacy and has been approved for the treatment of non-small cell lung cancer (NSCLC) and solid tumors. However, whether entrectinib affects the activities of recombinant human UDP-glucuronosyltransferases (UGTs) remains unclear. Herein, we aimed to investigate the inhibitory effects of entrectinib on human UGTs and to assess the potential risk of causing drug-drug interactions (DDIs) based on the inhibition against UGTs. High-performance liquid chromatography (HPLC) was used to evaluate the inhibitory effects of entrectinib on UGTs according to the product formation rate of UGT substrate with or without entrectinib, and the inhibition kinetics experiment was conducted to assess the inhibitory type of entrectinib on UGTs. Our results showed that entrectinib exhibited extensive inhibitory effects on most human UGTs, and especially inhibited the activities of UGT1A7, UGT1A8, and UGT2B15 with Ki (Inhibition constant) of lower than 5 µM (0.95-4.38 µM). Furthermore, the results from quantitative prediction research suggested that the combination of entrectinib at 600 mg/day with substrates primarily metabolized by hepatic UGT2B15 or intestinal UGT1A7 and UGT1A8 might cause clinical DDIs. Thus, special attention should be paid to avoid adverse reactions induced by DDIs when co-administration of entrectinib and drugs metabolized by UGTs.

RBM3 is an outstanding cold shock protein with multiple physiological functions beyond hypothermia.

RNA-binding motif protein 3 (RBM3), an outstanding cold shock protein, is rapidly upregulated to ensure homeostasis and survival in a cold environment, which is an important physiological mechanism in response to cold stress. Meanwhile, RBM3 has multiple physiological functions and participates in the regulation of various cellular physiological processes, such as antiapoptosis, circadian rhythm, cell cycle, reproduction, and tumogenesis. The structure, conservation, and tissue distribution of RBM3 in human are demonstrated in this review. Herein, the multiple physiological functions of RBM3 were summarized based on recent research advances. Meanwhile, the cytoprotective mechanism of RBM3 during stress under various adverse conditions and its regulation of transcription were discussed. In addition, the neuroprotection of RBM3 and its oncogenic role and controversy in various cancers were investigated in our review.

O-GlcNAcylation: The Underestimated Emerging Regulators of Skeletal Muscle Physiology.

O-GlcNAcylation is a highly dynamic, reversible and atypical glycosylation that regulates the activity, biological function, stability, sublocation and interaction of target proteins. O-GlcNAcylation receives and coordinates different signal inputs as an intracellular integrator similar to the nutrient sensor and stress receptor, which target multiple substrates with spatio-temporal analysis specifically to maintain cellular homeostasis and normal physiological functions. Our review gives a brief description of O-GlcNAcylation and its only two processing enzymes and HBP flux, which will help to better understand its physiological characteristics of sensing nutrition and environmental cues. This nutritional and stress-sensitive properties of O-GlcNAcylation allow it to participate in the precise regulation of skeletal muscle metabolism. This review discusses the mechanism of O-GlcNAcylation to alleviate metabolic disorders and the controversy about the insulin resistance of skeletal muscle. The level of global O-GlcNAcylation is precisely controlled and maintained in the "optimal zone", and its abnormal changes is a potential factor in the pathogenesis of cancer, neurodegeneration, diabetes and diabetic complications. Although the essential role of O-GlcNAcylation in skeletal muscle physiology has been widely studied and recognized, it still is underestimated and overlooked. This review highlights the latest progress and potential mechanisms of O-GlcNAcylation in the regulation of skeletal muscle contraction and structural properties.

Immune characteristics of children with autoimmune encephalitis and the correlation with a short-term prognosis.

BACKGROUND: Autoimmune encephalitis (AE) is a type of encephalopathy mediated by an antigenic immune response in the central nervous system. Most research related to autoimmune encephalitis (AE) is focused on early diagnosis, treatment and prognosis analysis; there has been little research conducted on the characteristics of immune function, and the relationship between immune function and prognoses of patients with autoimmune encephalitis needs to be studied further. METHODS: A total of 33 children with autoimmune encephalitis were identified through the clinic database and inpatient consults at Tianjin Children's Hospital from January 2013 to January 2021. Based on the one-year follow-up and the modified Rankin Scale (mRS) prognosis score, they were divided into a good prognosis group and a poor prognosis group. The immune function characteristics of the two groups of children with autoimmune encephalitis (AE) were compared using Spearman correlation to analyse the mRS score and immune function indicators (IgA, IgG, IgM, CD4, CD8, CD4/CD8), and binary logistic regression was used to analyse the independent risk factors of the prognoses in patients with autoimmune encephalitis (AE). RESULTS: The differences in abnormal mental disorders and limb dyskinesia, cognitive impairment, onset types, modified Rankin Scale (mRS) scores at admission, and immune function status during remission between the two groups were statistically significant (p < 0.05). CONCLUSION: There is a close correlation between modified Rankin Scale (mRS) scores and the immune function index CD4/CD8 in children with autoimmune encephalitis (AE) when they are admitted to the hospital. A young age, disturbance of consciousness, limb dyskinesia, abnormal immune function in remission and anti-NMDAR encephalitis are risk factors for poor prognoses in children with autoimmune encephalitis (AE). Clinical treatment requires more attention.

Near-Infrared Afterglow Semiconducting Nano-Polycomplexes for the Multiplex Differentiation of Cancer Exosomes.

The detection of exosomes is promising for the early diagnosis of cancer. However, the development of suitable optical sensors remains challenging. We have developed the first luminescent nanosensor for the multiplex differentiation of cancer exosomes that bypasses real-time light excitation. The sensor is composed of a near-infrared semiconducting polyelectrolyte (ASPN) that forms a complex with a quencher-tagged aptamer. The afterglow signal of the nanocomplex (ASPNC), being initially quenched, is turned on in the presence of aptamer-targeted exosomes. Because detection of the afterglow takes place after the excitation, background signals are minimized, leading to an improved limit of detection that is nearly two orders of magnitude lower than that of fluorescence detection in cell culture media. Also, ASPNC can be easily tailored to detect different exosomal proteins by changing the aptamer sequence. This enables an orthogonal analysis of multiple exosome samples, potentially permitting an accurate identification of the cellular origin of exosomes for cancer diagnosis.

Two-stage cyclic enzymatic amplification method for ultrasensitive electrochemical assay of microRNA-21 in the blood serum of gastric cancer patients.

MicroRNA (miRNA) is riveting nowadays due to its close relevance to human malignancies. Exploiting a fast and convenient biosensor for sensitive and specific detecting miRNA is necessary and it has significant meaning for oncology. In this work, to understand the relationship between miRNA-21 and gastric cancer, we employ T4 RNA ligase 2 to initiate specific ligation reaction depending on the sequence of target RNA, and T7 exonuclease to catalyze the first stage cyclic enzymatic amplification method (CEAM) specifically, which also resting on the target RNA sequence, and the second stage CEAM to further amplify the response resulting from the initial target RNA. Our two-stage CEAM strategy can detect miRNA-21 as low as 0.36fM with remarkable specificity, and most importantly, it can be used to inspect the expression level of miRNA-21 in blood serum of gastric cancer patients. This will offer new perspective for figuring out the pathways of miRNA-21 involving in cancer.