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N(6)-methyladenosine (m(6)A) modification in RNA affects various aspects of RNA metabolism and regulates gene expression. This modification is modulated by many regulatory proteins, such as m(6)A methyltransferases (writers), m(6)A demethylases (erasers), and m(6)A-binding proteins (readers). Previous studies have suggested that alterations in m(6)A regulatory proteins induce genome-wide alternative splicing in many cancer cells. However, the functional effects and molecular mechanisms of m(6)A-mediated alternative splicing have not been fully elucidated. To understand the consequences of this modification on RNA splicing in cancer cells, we performed RNA sequencing and analyzed alternative splicing patterns in METTL3-knockdown osteosarcoma U2OS cells. We detected 1,803 alternatively spliced genes in METTL3-knockdown cells compared to the controls and found that cell cycle-related genes were enriched in differentially spliced genes. A comparison of the published MeRIP-seq data for METTL14 with our RNA sequencing data revealed that 70-87% of alternatively spliced genes had an m(6)A peak near 1 kb of alternative splicing sites. Among the 19 RNA-binding proteins enriched in alternative splicing sites, as revealed by motif analysis, expression of SFPQ highly correlated with METTL3 expression in 12,839 TCGA pan-cancer patients. We also found that cell cycle-related genes were enriched in alternatively spliced genes of other cell lines with METTL3 knockdown. Taken together, we suggest that METTL3 regulates m(6)A-dependent alternative splicing, especially in cell cycle-related genes, by regulating the functions of splicing factors such as SFPQ.

The homing of M1 and M2 macrophages may play distinct roles in the tumor microenvironment (TME). However, these roles of macrophages in the TME remain unclear. We downloaded RNA sequencing data from The Cancer Genome Atlas (TCGA) database for patients with CRC. Subsequently, Kaplan-Meier survival curves were generated to assess the differential infiltration of M1 and M2 macrophages based on CRC location. Differentially expressed gene (DEG) and functional analyses were performed to screen the roles of DEGs. Critical prognostic genes were identified using least absolute shrinkage and selection operator regression. The risk scores were calculated for each patient. In patients with right-sided CRC, reduced M1 macrophage infiltration was associated with poor prognosis. M1 macrophage infiltration positively correlated with CD8+ T cell infiltration. A risk model was developed and validated for performance using GSE103479 and GSE72970. Nine genes were identified as independent prognostic genes that could be potential biomarkers for effectively predicting survival in patients with right-sided CRC. Kaplan-Meier curves for overall survival and progression-free survival analyses revealed that the high-risk group of patients with right-sided CRC had a poor prognosis. This novel M1 macrophage-related risk model may provide a gene signature for predicting the survival outcomes of patients with right-sided CRC and facilitate further studies examining the relationship between infiltration of M1 macrophages and the prognosis of such patients.

Background Amputation in the upper extremities influenced the quality of life a lot adversely. So, replantation was tried in many cases of amputation. Especially, due to good plasticity and healing capacity, replantation in children should be actively attempted. On the contrary, owing to growth potential in children, there are several late complications to happen like shortening and synostosis. There are only a few longterm follow-up reports of paediatric patients after replantation of upper extremities. We report a case of successful distal forearm replantation in a 2-year-old child who sustained a wringer injury by a sawing machine with a follow-up of 30 years. Case description A 2-year-old female patient was brought to our institution after a wringer injury to the distal forearm by a sawing machine. She sustained a near-total amputation at the distal forearm level with only a skin tag. Replantation was performed 4 hours after the injury. Radius and ulnar fractures were fixed with Kirschner and roll wires. The radial and ulnar arteries were anastomosed and three veins were anastomosed too. The median, ulnar, and radial nerves were managed by epi-perineurorrhaphy. The muscles were readapted, flexor tendons were performed tenorrhaphy each by each, and extensor tendons were performed grouping tenorrhaphy. Ten years after the replantation, a supination motion block was developed but successfully managed. Conclusion Replantation of upper limbs in children is an eceedingly worthwhile procedure. Though due to growth potential several complications were developed unlikely in adults. But those can be improved with additional procedures. Good plasticity and healing capacity of children make good functional outcomes in long-term follow-up. So, replantation of upper limbs in children should essentially be considered and aggressively performed. How to cite this article Hee LS, Hyung-Sik K, Hong-Chul L. Distal Forearm Replantation in a Child: A Case Report with a 30-year Followup. Strategies Trauma Limb Reconstr 2021;16(3):179–183.

Alkaloids are a large cluster of molecules found in Mother Nature all over the world. They are all secondary compounds and collection of miscellaneous elements and biomolecules, derived from amino acids or from transamination. This diverse chemical group is categorized, based on the amino acids that deliver their nitrogen atom and part of their skeleton. Alkaloids from a similar origin or having the same basic nucleus may have dissimilar biosynthetic pathways and different biological activity. They are derived from l-phenylalanine, l-tyrosine, anthranilic acid or acetate, l-histidine, l-ornithine, nicotinic acid, and l-lysine. Apart from other types of alkaloids, indole, tropane, and isoquinoline alkaloids are very important. People from all over the world are using them in their everyday life. Alkaloids can also have an animal origin, which may be endogenous or exogenous. This chapter highlights the phytochemistry of the main representatives among the diverse group of alkaloids. This chapter also focuses on their extraction, purification, fractionation, identification, and quantification procedures. A fundamental understanding of the biological activity of important alkaloids is also highlighted in this chapter. With the potential of revealing new compounds and diverse pharmacological properties, alkaloids still embrace a great potential for the future of drug discovery.

Objectives Factors predictive of the severity of and recovery from Bell’s palsy remain unclear. This study evaluated the association between neutrophil to lymphocyte ratio (NLR) and the severity of and recovery from Bell’s palsy. Methods This retrospective study included 51 patients who were hospitalized with Bell’s palsy from 2015 to 2017. Degree of paralysis was assessed by House-Brackmann (H-B) grade. Patients with H-B grades 2–4 were classified as having mild to moderate palsy and patients with H-B grade 5 or 6 were classified as having severe palsy. Patients were evaluated for obesity, hypertension and diabetes mellitus, and blood tests were performed to determine NLR and platelet to lymphocyte ratio. Patients were treated with steroids and antiviral agents. H-B grade was assessed 1 week, 1 month, and 3 months after treatment. Results NLR was significantly higher in patients with severe than with mild to moderate palsy (P=0.048). Recovery time was significantly longer in patients with high NLR than low NLR (P=0.045). Conclusion Higher NLR in patients with Bell’s palsy was associated with longer recovery time. NLR may be prognostic of recovery time in patients with Bell’s palsy.

To find out the combination of the extracts from Paeonia lactiflora Pallas (PL), Reh- mannia Glutinosa var. Purpurea Makino (RG), Perilla Frutescens var. Acuta Kudo (PF) to increase endometrial receptivity.Herbal medicines were extracted with boiling water and polysaccharides were removed. We examined the effect of PL, RG, and PF (PRP), a most effective herbal formula deduced from constitutive ingredient herbs of Antai Yin which is composed of PRP, on the leukemia inhibitory factor (LIF) expression and endometrial receptivity.The combination of the extracts from PRP induced the LIF expression in Ishikawa cells and increased the adhesion between Ishikawa and JAr cells. In addition, PRP-induced attachment of JAr cells onto Ishikawa cells and expression of adhesion molecules, ITGAV, ITGB5, CD44s, and L-selectin, are significantly reduced by knock-down of LIF expression.Induced by the combination of the PRP extracts, the adhesion between trophoblast and endometrial cells are mediated by expression of LIF and adhesion molecules. Thus, we suggest the combination of the PRP extracts may be a novel therapy for enhancing embryo implantation rate.

Mesenchymal stem cells (MSCs) have been reported to possess regulatory functions on immune cells which make them alternative therapeutics for the treatment of inflammatory and autoimmune diseases. The interaction between MSCs and immune cells through paracrine factors might be crucial for these immunomodulatory effects of MSCs. Extracellular vesicles (EVs) are defined as bilayer membrane structures including exosomes and microvesicles which contain bioactive paracrine molecules affecting the characteristics of target cells. Recently, several studies have revealed that EVs derived from MSCs (MSC-EVs) can reproduce similar therapeutic impacts of parent MSCs; MSC-EVs could regulate proliferation, maturation, polarization, and migration of various immune effector cells and modulate the immune microenvironment depending on the context by delivering inflammatory cytokines, transcription factors, and microRNAs. Therefore, MSC-EVs can be applied as novel and promising tools for the treatment of immune-related disorders to overcome the limitations of conventional cell therapy regarding efficacy and toxicity issues. In this review, we will discuss current insights regarding the major outcomes in the evaluation of MSC-EV function against inflammatory disease models, as well as immune cells.

Blood transfusions hold an indispensable part in the modern healthcare system. Up to date, the blood supply is largely dependent on donations. Unfortunately, collecting the clinical-grade blood products has become a challenging mission due to accelerated population aging, which not only increases the need for blood transfusions but also decreases the number of healthy donors. Moreover, individuals with severe hematological abnormalities or rare blood phenotypes need alternative therapeutic approaches instead of conventional blood transfusion. In these aspects, the concept of in vitro/ex vivo production of blood cells has been emerging and many attempts have been focused on manufacturing mature erythrocytes, so-called red blood cells (RBCs), the most common and important component among the blood derivatives. In this review, we provide a general overview regarding the current strategies for generating RBCs from various stem cell sources including pluripotent stem cells (PSCs) as well as circulating blood stem cells and the remaining challenges that must be overcome prior to their practical application.

The supply of highly concentrated oxygen positively affects cognitive processing in normal young adults. However, there have been few reports on changes in cognitive ability in elderly subjects following highly concentrated oxygen administration. This study investigated changes in cognitive ability, blood oxygen saturation (%), and heart rate (beats/min) in normal elderly subjects at three different levels of oxygen [21% (1 L/min), 93% (1 L/min), and 93% (5 L/min)] administered during a 1-back task. Eight elderly male (75.3 ± 4.3 years old) and 10 female (71.1 ± 3.9 years old) subjects, who were normal in cognitive ability as shown by a score of more than 24 points in the Mini-Mental State Examination-Korea, participated in the experiment. The experiment consisted of an adaptation phase after the start of oxygen administration (3 minutes), a control phase to obtain stable baseline measurements of heart rate and blood oxygen saturation before the task (2 minutes), and a task phase during which the 1-back task was performed (2 minutes). Three levels of oxygen were administered throughout the three phases (7 minutes). Blood oxygen saturation and heart rate were measured during each phase. Our results show that blood oxygen saturation increased, heart rate decreased, and response time in the 1-back task decreased as the concentration and amount of administered oxygen increased. This shows that administration of sufficient oxygen for optimal cognitive functioning increases blood oxygen saturation and decreases heart rate.

In this study, a constant pressure stimulus was applied on the 3 joints (first [p1], second [p2], and third [p3] joints) of 4 fingers (index, middle, ring, and little fingers), and the activation areas within Brodmann area 2 (BA 2) were compared for these different fingers and joints by using functional magnetic resonance imaging. Eight healthy male college students (25.4 ± 1.32 years) participated in the study. Each session was composed of 3 blocks, and each block was composed of a Control phase (30 seconds) and a Pressure phase (30 seconds). No pressure stimulus was applied in the Control phase, during which the subjects would simply lay comfortably with their eyes closed. In the Pressure phase, a pressure stimulus was applied onto one of the joints of the selected finger. For each finger and joint, BA 2 areas activated by the pressure stimulus were extracted by the region of interest method. There was a significant difference in the activation areas for the different fingers (P = .042) as well as for the different joints (P = .050). The activation area decreased in the order of the little, index, and middle fingers, as well as in the order of p1, p3, and p2.