• Title/Summary/Keyword: therapeutic potential

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Sarcoma Immunotherapy: Confronting Present Hurdles and Unveiling Upcoming Opportunities

  • Sehan Jeong;Sharmin Afroz;Donghyun Kang;Jeonghwan Noh;Jooyeon Suh;June Hyuk Kim;Hye Jin You;Hyun Guy Kang;Yi-Jun Kim;Jin-Hong Kim
    • Molecules and Cells
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    • v.46 no.10
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    • pp.579-588
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    • 2023
  • Sarcomas are rare and heterogeneous mesenchymal neoplasms originating from the bone or soft tissues, which pose significant treatment challenges. The current standard treatment for sarcomas consists of surgical resection, often combined with chemo- and radiotherapy; however, local recurrence and metastasis remain significant concerns. Although immunotherapy has demonstrated promise in improving long-term survival rates for certain cancers, sarcomas are generally considered to be relatively less immunogenic than other tumors, presenting substantial challenges for effective immunotherapy. In this review, we examine the possible opportunities for sarcoma immunotherapy, noting cancer testis antigens expressed in sarcomas. We then cover the current status of immunotherapies in sarcomas, including progress in cancer vaccines, immune checkpoint inhibitors, and adoptive cellular therapy and their potential in combating these tumors. Furthermore, we discuss the limitations of immunotherapies in sarcomas, including a low tumor mutation burden and immunosuppressive tumor microenvironment, and explore potential strategies to tackle the immunosuppressive barriers in therapeutic interventions, shedding light on the development of effective and personalized treatments for sarcomas. Overall, this review provides a comprehensive overview of the current status and potential of immunotherapies in sarcoma treatment, highlighting the challenges and opportunities for developing effective therapies to improve the outcomes of patients with these rare malignancies.

Anti-Inflammatory Activities of (+)-Afzelechin against Lipopolysaccharide-Induced Inflammation

  • In-Chul Lee;Jong-Sup Bae
    • Biomolecules & Therapeutics
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    • v.32 no.4
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    • pp.467-473
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    • 2024
  • In this study, we investigated the potential protective effects of (+)-afzelechin (AZC), a natural compound that is derived from Bergenia ligulata, on lipopolysaccharide (LPS)-induced inflammatory responses. AZC is known to have antioxidant, anticancer, antimicrobial, and cardiovascular protective properties. However, knowledge regarding the therapeutic potential of AZC against LPS-induced inflammatory responses is limited. Thus, we investigated the protective attributes of AZC against inflammatory damage caused by LPS exposure. We examined the effects of AZC on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). In addition, the effects of AZC on the expression of iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were analyzed in the lung tissues of LPS-injected mice. Data revealed that AZC promoted the production of HO-1, inhibited the interaction between luciferase and nuclear factor (NF)-κB, and reduced the levels of COX-2/PGE2 and iNOS/NO, thereby leading to a decrease in the signal transducer and activator of transcription (STAT)-1 phosphorylation. Moreover, AZC facilitated the nuclear translocation of Nrf2, increased the binding activity between Nrf2 and the antioxidant response elements (AREs), and lowered the expression of IL-1β in the LPS-treated HUVECs. In the animal model, AZC significantly reduced the expression of iNOS in the lung tissue structure and the TNF-α level in the bronchoalveolar lavage fluid. These findings demonstrate that AZC possesses anti-inflammatory properties that regulate iNOS through the inhibition of both NF-κB expression and p-STAT-1. Consequently, AZC has potential as a future candidate for the development of new clinical substances for the treatment of pathological inflammation.

Constipation anti-aging effects by dairy-based lactic acid bacteria

  • Mohamad Hafis Jaafar;Pei Xu;Uma-Mageswary Mageswaran;Shandra-Devi Balasubramaniam;Maheswaran Solayappan;Jia-Jie Woon;Cindy Shuan-Ju Teh;Svetoslav Dimitrov Todorov;Yong-Ha Park;Guoxia Liu;Min-Tze Liong
    • Journal of Animal Science and Technology
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    • v.66 no.1
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    • pp.178-203
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    • 2024
  • Constipation, which refers to difficulties in defecation and infrequent bowel movement in emptying the gastrointestinal system that ultimately produces hardened fecal matters, is a health concern in livestock and aging animals. The present study aimed to evaluate the potential effects of dairy-isolated lactic acid bacteria (LAB) strains to alleviate constipation as an alternative therapeutic intervention for constipation treatment in the aging model. Rats were aged via daily subcutaneous injection of D-galactose (600 mg/body weight [kg]), prior to induction of constipation via oral administration of loperamide hydrochloride (5 mg/body weight [kg]). LAB strains (L. fermentum USM 4189 or L. plantarum USM 4187) were administered daily via oral gavage (1 × 10 Log CFU/day) while the control group received sterile saline. Aged rats as shown with shorter telomere lengths exhibited increased fecal bulk and soften fecal upon administration of LAB strains amid constipation as observed using the Bristol Stool Chart, accompanied by a higher fecal moisture content as compared to the control (p < 0.05). Fecal water-soluble metabolite profiles showed a reduced concentration of threonine upon administration of LAB strains compared to the control (p < 0.05). Histopathological analysis also showed that the administration of LAB strains contributed to a higher colonic goblet cell count as compared to the control (p < 0.05). The present study illustrates the potential of dairy-sourced LAB strains as probiotics to ameliorate the adverse effect of constipation amid aging, and as a potential dietary intervention strategy for dairy foods including yogurt and cheese.

Allergenicity Reduction of Milk (우유에서의 알레르겐 저감화 방법)

  • Ha, Woel-Kyu
    • Journal of Dairy Science and Biotechnology
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    • v.26 no.1
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    • pp.27-36
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    • 2008
  • This review was written to introduce updated data on the structure and function of the major milk proteins identified as allergens, the characterization of their epitopes in each allergenic milk proteins, and the reduction of milk protein allergenicity. Most mammalian milk protein, even protein present at low concentration, are potential allergens. Epitopes identified in milk proteins are both conformational(structured epitope) and sequential epitopes(linear epitope), throughout the protein molecules. Epitopes on casein and whey proteins are reported to be sequential epitope and conformational epitopes, respectively. Conformational epitopes on whey protein are changed into sequential epitope by heat denaturation during heat treatment. Several methods have been proposed to reduce allergenicity of milk proteins. Most ideal and acceptable method to make hypoallergenic milk or formula, so far, is the hydrolysis of allergenic milk proteins by enzymes that has substrate specificity, such as pepsin, trypsin, or chymotrypsin. Commercial formulas based on milk protein hydrolysate are available for therapeutic purpose, hypoantigenic formula for infants from families with a history of milk allergy and hypoallergenic formula for infants with existing allergic symptoms.

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Aptamers as Functional Nucleic Acids: in vitro Selection and Biotechnological Applications

  • You, Kyung-Man;Lee, Sang-Hyun;Aesul Im;Lee, Sun-Bok
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.8 no.2
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    • pp.64-75
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    • 2003
  • Aptamers are functional nucleic acids that can specially bind to proteins, peptides, amino acids. nucleotides, drugs, vitamins and other organic and inorganic compounds. The aptamers are identified from random DNA or RNA libraries by a SELEX (systematic evolution of ligands by exponential amplification) process. As aptamers have the advantage, and potential ability to be released from the limitations of antibodies, they are attractive to a wide range of therapeutic and diagnostic applications. Aptamers, with a high-affinity and specificity, could fulfil molecular the recognition needs of various fields in biotechnology. In this work, we reviewed some aptamer Selection techniques, properties, medical applications of their molecules and their biotechnological applications, such as ELONA (enzyme linked oligonucleotide assay), flow cytometry, biosensors, electrophoresis, chromatography and microarrays.

Can herbal drug(s) meet the challenges of genomewide screen results on rheumatoid arthritis

  • Paul, Bholanath
    • Advances in Traditional Medicine
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    • v.5 no.4
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    • pp.251-261
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    • 2005
  • Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder with a complex genetic component. RA is characterized by chronic inflammation of the synovial membrane in the joint, which leads to the progressive destruction of articular cartilage, ligament and bone. Several cytokines such as tumor necrosis $factor-{\alpha}\;TNF-{\alpha}\;and\;interleukin-1{\beta}\;(IL-1{\beta})$ and interleukin-6 (IL-6) have been implicated in the pathological mechanisms of synovial tissue proliferation, joint destruction and programmed cell death in rheumatoid joint. Genome wide screening of subjects suffering from autoimmune diseases especially arthritis revealed linkage to inflammatory molecules like $TNF-{\alpha},\;IL-1{\beta}$ and IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappaB $(NF-{\kappa}B)$ and human leucocyte antigen/major histocompatibility complex (HLA/MHC) locus. The status of the pharmacological mechanism of herbal drugs in the light of genome wide screening results has been discussed to reinforce the therapeutic potential and the pharmacological basis of the herbal drugs.

MicroRNA-1 in Cardiac Diseases and Cancers

  • Li, Jianzhe;Dong, Xiaomin;Wang, Zhongping;Wu, Jianhua
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.5
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    • pp.359-363
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    • 2014
  • MicroRNAs (miRs) are endogenous ${\approx}22$-nt non-coding RNAs that participate in the regulation of gene expression at post-transcriptional level. MiR-1 is one of the muscle-specific miRs, aberrant expression of miR-1 plays important roles in many physiological and pathological processes. In this review, we focus on the recent studies about miR-1 in cardiac diseases and cancers. The findings indicate that miR-1 may be a novel, important biomarker, and a potential therapeutic target in cardiac diseases and cancers.

Microbial Subversion of Heparan Sulfate Proteoglycans

  • Chen, Ye;Gotte, Martin;Liu, Jian;Park, Pyong Woo
    • Molecules and Cells
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    • v.26 no.5
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    • pp.415-426
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    • 2008
  • The interactions between the host and microbial pathogen largely dictate the onset, progression, and outcome of infectious diseases. Pathogens subvert host components to promote their pathogenesis and, among these, cell surface heparan sulfate proteoglycans are exploited by many pathogens for their initial attachment and subsequent cellular entry. The ability to interact with heparan sulfate proteoglycans is widespread among viruses, bacteria, and parasites. Certain pathogens also use heparan sulfate proteoglycans to evade host defense mechanisms. These findings suggest that heparan sulfate proteoglycans are critical in microbial pathogenesis, and that heparan sulfate proteoglycan-pathogen interactions are potential targets for novel prophylactic and therapeutic approaches.

Airway Stenting in Tracheobronchial Diseases : Silastic stenting (기도질환에서 실리콘 기도스텐트 치료)

  • Kim, Ho-Joong
    • Korean Journal of Bronchoesophagology
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    • v.10 no.2
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    • pp.5-8
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    • 2004
  • Stenosing airway disease is classified as intraluminal obstruction, extrinsic compression, and malacia by the anatomical site of the lesion. Stenting therapy is indicated for symptomatic relief of life-threatening dyspnea caused by the last two types. Airway stents are made with metal mesh and/or silicone rubber, and currently more than 20 kinds of stent are available. Among many kinds of silicone stent, the Dumon stent is mostly widely used for benign and malignant airway stenoses, but general anesthesia and rigid bronchoscopy are needed for insertion. It can be removed when the stenosing airway disease subsides completely. In many clinical studies, most patients $(85-90\%)$ improved immediately after stenting, and procedure-related mortality was low $(<3\%)$ in experienced centers. Stent displacement, mucus impaction, and granulation tissue formation are potential complications. Stenting is one of many effective therapeutic modalities for stenosing central airway disease. Careful patient selection, experiences, and continuous development of new technology will bring better results.

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The Role of Inflammatory Mediators in the Pathogenesis of Nonalcoholic Fatty Liver Disease

  • Kim, Joon Sung
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.15 no.2
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    • pp.74-78
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    • 2012
  • With a markedly increased prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) now becomes the most common cause of chronic liver disease in both adults and children. The etiology and pathogenesis of NAFLD are multifactorial and remain incompletely understood. According to the "two-hit" theory, inflammatory cytokines and adipokines are activated by oxidative stress and they are involved in insulin resistance, necroinflammatory steatohepatitis and fibrosis. This review discusses the latest updates on the role of some of important inflammatory adipokines and cytokines in the pathogenesis of NAFLD with an emphasis on their potential therapeutic implications.