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The cellular process responsible for the degradation of cytosolic proteins and subcellular organelles in lysosomes was termed "autophagy." This process occurs at a basal level in most tissues as part of tissue homeostasis that redounds to the regular turnover of components inside cytoplasm. The breakthrough in the autophagy field is the identification of key players in the autophagy pathway, compounded under the name "autophagy-related genes" (ATG) encoding for autophagy effector proteins. Generally, the function of autophagy can be classified into two divisions: intracellular clearance of defective macromolecules and organelles and generation of degradation products. Therapeutic strategies using stem cell-based approach come as a promising therapy and develop rapidly recently as stem cells have high self-renewability and differentiation capability as known as mesenchymal stem cells (MSCs). They are defined as adherent fibroblast-like population with the abilities to self-renew and multi-lineage differentiate into osteogenic, adipogenic, and chondrogenic lineage cells. To date, they are the most extensively applied adult stem cells in clinical trials. The properties of MSCs, such as immunomodulation, neuroprotection, and tissue repair pertaining to cell differentiation, processes to replace lost, or damaged cells, for aiding cell repair and revival. Autophagy has been viewed as a remarkable mechanism for maintaining homeostasis, ensuring the adequate function and survival of long-lived stem cells. In addition, authophagy also plays a remarkable role in protecting stem cells against cellular stress when the stem cell regenerative capacity is harmed in aging and cellular degeneration. Understanding the under-explored mechanisms of MSC actions and expanding the spectrum of their clinical applications may improve the utility of the MSC-based therapeutic approach in the future.

BACKGROUND Heart diseases, especially myocardial ischemia, remain one of the leading causes of mortality worldwide and usually result in irreparable cardiomyocyte damage and severe heart failure. Recent advances in induced pluripotent stem cell (iPSC) technologies for applied regenerative medicine and stem cell research, especially for iPSC-derived cardiomyocytes have increased the hope for heart repair. However, the driver molecules of myocardial differentiation and the functional reconstruction capacity of iPSC-derived cardiomyocytes are still questionable. METHODS Herein, we established a rapid differentiated platform that is involved in cardiomyogenic differentiation and maturation from iPSCs in vitro. Functional analysis is performed in miR-181a-transfected iPSC-derived cardiomyocyte (iPSC-cardio/miR-181a) under a time-lapse microscope. In addition, we calculated the beating area and frequency of iPSC-cardio/miR-181a cells in the presence of HCN4 shRNA or miR-181a SPONGE. RESULTS miR-181a enhanced the beating area and maintained the beating frequency of iPSC-derived cardiomyocytes by enhancing HCN4 expression. CONCLUSION miR-181a would play a key role on maintaining proper beating function in iPSC-derived cardiomyocytes.

Lung cancer (LC) is a major killer disease globally. This situation is further supported by yearly increase in new LC cases and its poor 5-year survival which is less than 15%. Although a large percentage of LC cases have been attributed to smoking, a considerable amount of nonsmokers also develops this disease, thereby suggesting a genetic and/or epigenetic undertone to LC development. Several growth-related genes such as epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) as well as tumor suppressor genes such as p53 have been implicated in LC pathogenesis and progression. Likewise, the genome only contains approximately 1% of coding regions. Hence, noncoding portion of the genome such as noncoding RNAs (ncRNAs) has been studied and discovered to play a cogent role in LC pathogenesis. More precisely, microRNAs (miRNAs) and long ncRNAs (lncRNAs) have been studied for decades. Posttranscriptional gene modulation function of miRNAs is well established and characterized. Likewise, the antagonizing interaction between lncRNAs and miRNAs had also been proven to further control gene expression during healthy and disease conditions like LC. More recently, renewed attention toward circular RNAs [circular RNAs (circRNAs)] study showed that circRNAs can also sponge miRNAs to modulate gene expressions too. Hence, miRNAs, lncRNAs, and circRNAs seem to function within a circuit to optimally determine which gene is needed to be upregulated or downregulated in biological system. Therefore, this review will discuss important ncRNAs, namely miRNA, lncRNA, and circRNA in LC progression. Paracrine effect of exosomal ncRNA will be also reviewed. In addition, the prospect of these ncRNAs in enhancing better LC treatment will be highlighted as well.

Pulmonary arterial hypertension (PAH) was a disease predominantly affecting young females about 40 years ago; however, it has been increasingly diagnosed in elderly individuals. Few studies have investigated the features of elderly patients with PAH. This review provides an overview of the characteristics of elderly patients with PAH compared to young patients. The examination of the changing demographics of the population with PAH revealed that the mean age has increased over the years. In addition, the investigation into the diagnostic challenges in elderly patients with PAH revealed the difficulty in differentiating PAH from pulmonary hypertension secondary to diastolic heart failure. Moreover, it was noted that elderly patients underwent combination drug regimens less frequently and exhibited poorer treatment responses than young patients. Finally, it was found that elderly PAH patients experienced poorer survival than young patients. The differences among five survival prediction models and their applicability in predicting the prognosis of PAH patients are discussed.

Terrible triad of the elbow injury is difficult to manage, and the role of the coronoid process in instability is very important. We describe a simple, modified suture technique to fix a coronoid process fragment using suture anchor fixation.Eight patients (three female and five male) with coronoid process injuries with the fragment involving50% of the total height (Regan-Morrey type I/II) in terrible triad of elbow injury were included. Patients were treated operatively via a lateral Kocher's approach, and coronoid process fractures were repaired with a single pulley double-strand suture technique. Structures were addressed in a sequential fashion-the coronoid process, radial head, lateral ulnar collateral ligament.All patients were treated with the single pulley double-strand anchor suture technique and the coronoid process fragment was found to be in good contact with the original avulsion site using the method. The final Mayo Elbow Performance Score was excellent (90) in six patients and good (between 85 and 89) in two patients after operation 6 months.The single pulley double-strand suture tie method using a suture anchor is a less invasive and simpler fixation method for the repair of coronoid process fractures in patients with terrible triad of the elbow injuries and results in good outcomes.

The rapid spread of coronavirus disease (COVID-19) in many countries has caused inconvenience in conducting daily life activities, and even deaths. Dexamethasone is a corticosteroid applied in clinical medicine since 1957, especially in immune therapy fields. Herein, we present the characteristics of Dexamethasone, from molecular mechanisms such as genomic and nongenomic pathways by cellular signal regulations, to clinical applications in various phases of the disease. During COVID-19 pandemic, Dexamethasone given to patients who required oxygen or ventilation therapy showed improved life efficacy.

Background: Der f 7 and Der p 7 are important house dust mite allergens. An IgE-binding inhibition monoclonal antibody WH9 reacts ten folds stronger against Der p 7 than to Der f 7. The purpose of this study is to identify the antigenic determinant(s) and the structural basis of Der f 7 recognize by WH9. Methods: WH9-reactive determinant(s) on Der f 7 was identified by immunoblot and immunoblot inhibition. The 3-D binary complex structures of WH9 and the group 7 allergens were simulated with homology modeling and docking methods. Results: WH9 reacted with the Der f 7 f9 fragment. Among the five site-directed Der f 7 mutants, WH9 showed reduced immunoblot reactivity against Der f 7 S156A, D159A and P160A mutants. Only the wild-type protein and the Der f 7 I157A and L158A mutants can inhibit significantly the WH9-binding against Der f 7. The structural model of the Der f 7-WH9 complex suggests residues S156 and D159 of Der f 7 can bind to WH9 via potential hydrogen bonds. Conclusion: The structure models of Der f 7-WH9 and Der p 7-WH9 complexes revealed that the differential modes of binding of Der p 7 and Der f 7 allergens on WH9 contribute to the differential reactivity of WH9 against the Der f 7 and the Der p 7 mite allergens. Keywords: Der f 7, Der p 7, Homology modeling and docking, MoAb WH9

Best disease (BD), also termed Best vitelliform macular dystrophy (BVMD), is a juvenile-onset form of macular degeneration and central visual loss. In this report, we generated an induced pluripotent stem cell (iPSC) line, TVGH-iPSC-012-04, from the peripheral blood mononuclear cells of a female patient with BD by using the Sendai virus delivery system. The resulting iPSCs retained the disease-causing DNA mutation, expressed pluripotent markers and could differentiate into three germ layers. We believe that BD patient-specific iPSCs provide a powerful in vitro model for evaluating the pathological phenotypes of the disease.

Purpose Fusarium species are among prevalent airborne fungi and causative agents of human respiratory atopic disorders. We previously identified a 36.5-kDa F. proliferatum component recognized by IgE antibodies in 9 (53%) of the 17 F. proliferatum-sensitized atopic serum samples. The purpose of this study is to characterize the 36.5-kDa allergen of F. proliferatum. Methods Characterization of allergens and determination of IgE cross-reactivity were performed by cDNA cloning/expression and immunoblot inhibition studies. Results Based on the finding that the 36.5-kDa IgE-binding component reacted with the mouse monoclonal antibody FUM20 against fungal vacuolar serine protease allergens, the cDNA of F. proliferatum vacuolar serine protease (Fus p 9.0101) was subsequently cloned. Nine serum samples from respiratory atopic patients with IgE binding to the vacuolar serine protease allergen of Penicillium chrysogenum (Pen ch 18) also showed IgE-immunoblot reactivity to rFus p 9.0101. The purified rFus p 9.0101 can inhibit IgE and FUM20 binding to the 36.5-kDa component of F. proliferatum. Thus, a novel and important Fus p 9.0101 was identified. The rPen ch 18 can inhibit IgE binding to Fus p 9.0101. It indicates that IgE cross-reactivity between Fus p 9.0101 and Pen ch 18 also exists. Furthermore, neither rFus p 9.0101 K88A nor rPen ch 18 K89A mutants inhibited IgE binding to rFus p 9.0101. Lys88 was considered a critical core amino acid in IgE binding to r Fus p 9.0101 and a residue responsible for IgE cross-reactivity between Fus p 9.0101 and Pen ch 18 allergens. Conclusions Results obtained from this study indicate that vacuolar serine protease may be a major allergen of F. proliferatum and an important IgE cross-reactive pan-fungal allergen, and provide important bases for clinical diagnosis of fungal allergy.

The mechanisms of migration of neutrophils into the airway lumen are crucial in the development of airway injury of acute bronchiolitis and are mediated by adhesion molecules. In this study, we have attempted to evaluate the role of serum concentrations of the soluble form of intercellular adhesion molecule-1 (sICAM-1) in the disease activity in acute bronchiolitis and in respiratory syncytial virus (RSV) infection. Circulating levels of sICAM-1 in sera from 10 normal control subjects, and from 47 hospitalized acute bronchiolitis patients at admission, and from 25 patients on the day of discharge were determined by use of commercially available enzyme-linked immunosorbent assay kits. The mean serum level of sICAM-1 in bronchiolitis patients was significantly higher than in the 10 healthy control infants (345.8 +/- 99.7 microg/mL vs 237.1 +/- 81.7 microg/mL; p0.05). However, the mean sICAM-1 concentration was similar between RSV-positive and RSV-negative patients (337.5 +/- 99.6 microg/mL vs 350.9 +/- 101.1 microg/mL; p=0.65). Although the mean clinical severity score of RSV-positive patients was significantly higher than that of RSV-negative patients (5.94 +/- 1.83 vs 3.48 +/- 1.70; p0.05). The improvement of clinical severity score was not well correlated with the change of sICAM-1 level (r=0.22). This study provides evidence that serum levels of sICAM-1 are increased in acute bronchiolitis and further confirms the role of adhesion molecules involved in the pathogenesis of the disease. However, the serum concentrations of the soluble adhesion molecules could not reliably reflect the clinical severity of the disease.

Der p 7 is an important house dust mite allergen. However, antigenic determinants of Der p 7 are largely unknown. The purpose of this study is to analyze the determinants of Der p 7 and determine the structural basis of interactions between Der p 7 and WH9, an IgE-binding inhibition mouse monoclonal antibody (MoAb). IgE and WH9-reactive determinant(s) was identified by immunoblot using allergen mutants. A 3-D binary complex structure of Der p 7 and WH9 was simulated with homology modeling and docking methods. Our results obtained showed that among the five Der p 7 mutants (S156A, I157A, L158A, D159A, P160A), serum no. 1045 with IgE-binding against Der p 7 exhibited a reduced IgE immunoblot reactivity against Der p 7 L158A and D159A mutants. WH9 showed reduced immunoblot reactivity against S156A, L158A, D159A and P160A and the observation was confirmed by immunoblot inhibition. The WH9-binding determinant on Der p 7 containing S156, L158, D159 and P160 assumes a loop-like structure. The structural model of the Der p 7-WH9 complex suggests residues S156, I157, L158, D159 and P160 of Der p 7 contribute to WH9 binding via potential hydrogen bonds, electrostatic and hydrophobic interactions. In conclusion, MoAb WH9 interacts with critical residues L158 and D159 of Der p 7 and inhibits IgE-binding to Der p 7. Results obtained advance our understanding on molecular and structural bases of the antigenicity of Der p 7, its interactions with MoAb WH9 and facilitate the design of safer immunotherapy of human atopic disorders.

Rationale We have identified an alkaline serine protease that is a major allergen of Penicillium chrysogenum (Pen ch 13). The objective of the present study is to identify the linear IgE-binding epitopes of Pen ch 13. Methods The sequential IgE epitopes on Pen ch 13 were investigated with phage-displayed overlapping peptides, synthetic peptides attached on membranes, recombinant wild type Pen ch 13 and mutants carrying substituted amino acid(s). Results IgE antibodies in 35 serum samples tested reacted with at least one of the 11 peptide fragments of Pen ch 13. Peptide f-2n (residues 31 to 61) showed a high intensity and the highest frequency (77%) of IgE-binding. SPOTs assay narrowed down the IgE-binding to residues 48-55 (GHADFGGR). Substitution of His49 and/or Phe52 on Pen ch 13 with methionine resulted in proteins with drastic loss of IgE binding in seven sera tested. A model was constructed based on the structure of Penicillium cyclopium subtilisin protease that has over 90% (256 out of 283 amino acids) sequence identity with Pen ch 13. The major epitope (GHADFGGR) on Pen ch 13 formed a loop-like structure and located at the surface of the allergen. Conclusions Several linear IgE-reactive epitopes and their critical core amino acid residues were identified for the Pen ch 13 allergen. Mapping of these results on a 3D model of the allergen provides valuable information to elucidate the molecular basis of allergenicity for Pen ch 13.