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1.
Korean J Pain ; 34(4): 427-436, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34593660

RESUMO

Background: Pharmacological and non-pharmacological therapies have been used to treat patients with chemotherapy-induced peripheral neuropathy (CIPN). However, the effect of therapies in cancer patients has yet to be investigated comprehensively. We hypothesized that cyclic thermal therapy would improve blood flow and microcirculation and improve the symptoms driven by CIPN. Methods: The criteria of assessment were blood volume in region of interest (ROI) in the images, and European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 questionnaire scores. The blood volume was quantified by using red blood cell (RBC) scintigraphy. All patients were treated 10 times during 10 days. The thermal stimulations, between 15° and 41°, were repeatedly delivered to the patient's hands. Results: The total score of the questionnaires, the score of questions related to the upper limbs, the score of questions closely related to the upper limbs, and the score excluding the upper limbs questions was decreased. The blood volume was decreased, and the variance of blood volume was decreased. During cooling stimulation, the blood volume was decreased, and its variance was decreased. During warming stimulation, the blood volume was decreased, and its variance was decreased. Conclusions: We suggest that cyclic thermal therapy is useful to alleviate CIPN symptoms by blood circulation improvement. RBC scintigraphy can provide the quantitative information on blood volume under certain conditions such as stress, as well as rest, in peripheral tissue.

2.
Food Sci Nutr ; 9(9): 5083-5091, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34532017

RESUMO

Sarcopenia is a disease characterized by the loss of muscle mass and function that occurs mainly in older adults. The present study was designed to investigate the hypothesis that water extract of Lycium chinense (WELC) would improve muscle function and promote myogenesis for sarcopenia. We investigated the effect of water extracts of L. chinense on muscular endurance function and myogenesis to examine its efficacy in sarcopenia. Intake of WELC-containing cheese enhanced the muscular endurance function of mice in treadmill endurance tests. In addition, the cross-sectional areas of muscle fibers in the gastrocnemius muscle of L. chinense-fed mice were greater than that of control mice. Furthermore, WELC and its key component marker substance betaine promoted myogenesis of myoblasts by increasing the expression of the myogenic protein myosin heavy chain 3 (Myh3) and myotube formation. Taken together, our results suggest that L. chinense may potentially be useful in the development of preventive and therapeutic agents for sarcopenia, as well as in providing basic knowledge on myogenesis and muscular functions.

3.
Cell Biol Toxicol ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523043

RESUMO

The autophagy-mediated lysosomal pathway plays an important role in conferring stress tolerance to tumor cells during cellular stress such as increased metabolic demands. Thus, targeted disruption of this function and inducing lysosomal cell death have been proved to be a useful cancer therapeutic approach. In this study, we reported that octyl syringate (OS), a novel phenolic derivate, was preferentially cytotoxic to various cancer cells but was significantly less cytotoxic to non-transformed cells. Treatment with OS resulted in non-apoptotic cell death in a caspase-independent manner. Notably, OS not only enhanced accumulation of autophagic substrates, including lapidated LC3 and sequestosome-1, but also inhibited their degradation via an autophagic flux. In addition, OS destabilized the lysosomal function, followed by the intracellular accumulation of the non-digestive autophagic substrates such as bovine serum albumin and stress granules. Furthermore, OS triggered the release of lysosomal enzymes into the cytoplasm that contributed to OS-induced non-apoptotic cell death. Finally, we demonstrated that OS was well tolerated and reduced tumor growth in mouse xenograft models. Taken together, our study identifies OS as a novel anticancer agent that induces lysosomal destabilization and subsequently inhibits autophagic flux and further supports development of OS as a lysosome-targeting compound in cancer therapy. • Octyl syringate, a phenolic derivate, is preferentially cytotoxic to various cancer cells. • Octyl syringate destabilizes the lysosomal function. • Octyl syringate blocks the autophagic flux. • Octyl syringate is a potential candidate compound for cancer therapy.

4.
Sci Rep ; 11(1): 15931, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354133

RESUMO

Rubinstein-Taybi syndrome (RSTS) is a human genetic disorder characterized by distinctive craniofacial features, broad thumbs and halluces, and intellectual disability. Mutations in the CREB binding protein (CREBBP) and E1A binding protein p300 (EP300) are the known causes of RSTS disease. EP300 regulates transcription via chromatin remodeling and plays an important role in cell proliferation and differentiation. Plasminogen activator, urokinase (PLAU) encodes a serine protease that converts plasminogen to plasmin and is involved in several biological processes such as the proteolysis of extracellular matrix-remodeling proteins and the promotion of vascular permeability and angiogenesis. Recently, we discovered a patient who presented with RSTS-related skeletal anomaly and peripheral arterial vasculopathy. To investigate the genetic cause of the disease, we performed trio whole genome sequencing of the genomic DNA from the proband and the proband's parents. We identified two de novo variants coined c.1760T>G (p.Leu587Arg) and c.664G>A (p.Ala222Thr) in EP300 and PLAU, respectively. Furthermore, functional loss of EP300a and PLAUb in zebrafish synergistically affected the intersegmental vessel formation and resulted in the vascular occlusion phenotype. Therefore, we hypothesize that the de novo EP300 variant may have caused RSTS, while both the identified EP300 and PLAU variants may have contributed to the patient's vascular phenotype.

5.
Arch Biochem Biophys ; 710: 109004, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34364885

RESUMO

Transmembrane 4 L six family member 5 (TM4SF5) is involved in nonalcoholic steatosis and further aggravation of liver disease. However, its mechanism for regulating FA accumulation is unknown. We investigated how TM4SF5 in hepatocytes affected FA accumulation during acute FA supply. TM4SF5-expressing hepatocytes and mouse livers accumulated less FAs, compared with those of TM4SF5 deficiency or inactivation. Binding of TM4SF5 to SLC27A2 increased gradually upon acute FA treatment, whereas TM4SF5 constitutively bound SLC27A5. Suppression of either SLC27A2 or SLC27A5 in hepatocytes expressing TM4SF5 differentially modulated initial and maximal FA uptake levels for a fast turnover of fatty acid. Altogether, TM4SF5 negatively modulates FA accumulation into hepatocytes via association with the transporters for an energy homeostasis, when FA are supplied acutely.


Assuntos
Proteínas de Transporte de Ácido Graxo/metabolismo , Ácidos Graxos/metabolismo , Hepatócitos/metabolismo , Proteínas de Membrana/metabolismo , Animais , Transporte Biológico Ativo , Linhagem Celular , Metabolismo Energético , Proteínas de Transporte de Ácido Graxo/antagonistas & inibidores , Proteínas de Transporte de Ácido Graxo/genética , Células HEK293 , Células Hep G2 , Humanos , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Modelos Biológicos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Consumo de Oxigênio , RNA Interferente Pequeno/genética
6.
Mol Genet Metab Rep ; 28: 100783, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34354927

RESUMO

Hearing impairment is one of the complications in diabetes mellitus; however, there are very few therapeutic studies on it. In this study, we investigated the protective effect of alpha-lipoic acid (ALA) on hearing loss in diabetic transgenic zebrafish and confirmed that ALA protects the loss of hair cells (HCs) caused by hyperglycemia. The data indicated that ALA has a protective effect on the damage to HCs in diabetic zebrafish.

7.
Theranostics ; 11(16): 8092-8111, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335982

RESUMO

Active c-Src non-receptor tyrosine kinase localizes to the plasma membrane via N-terminal lipid modification. Membranous c-Src causes cancer initiation and progression. Even though transmembrane 4 L six family member 5 (TM4SF5), a tetraspan(in), can be involved in this mechanism, the molecular and structural influence of TM4SF5 on c-Src remains unknown. Methods: Here, we investigated molecular and structural details by which TM4SF5 regulated c-Src devoid of its N-terminus and how cell-penetrating peptides were able to interrupt c-Src activation via interference of c-Src-TM4SF5 interaction in hepatocellular carcinoma models. Results: The TM4SF5 C-terminus efficiently bound the c-Src SH1 kinase domain, efficiently to the inactively-closed form. The complex involved protein tyrosine phosphatase 1B able to dephosphorylate Tyr530. The c-Src SH1 domain alone, even in a closed form, bound TM4SF5 to cause c-Src Tyr419 and FAK Y861 phosphorylation. Homology modeling and molecular dynamics simulation studies predicted the directly interfacing residues, which were further validated by mutational studies. Cell penetration of TM4SF5 C-terminal peptides blocked the interaction of TM4SF5 with c-Src and prevented c-Src-dependent tumor initiation and progression in vivo. Conclusions: Collectively, these data demonstrate that binding of the TM4SF5 C-terminus to the kinase domain of inactive c-Src leads to its activation. Because this binding can be abolished by cell-penetrating peptides containing the TM4SF5 C-terminus, targeting this direct interaction may be an effective strategy for developing therapeutics that block the development and progression of hepatocellular carcinoma.


Assuntos
Proteína Tirosina Quinase CSK/metabolismo , Carcinoma Hepatocelular/metabolismo , Proteínas de Membrana/metabolismo , Proteína Tirosina Quinase CSK/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Genes src/genética , Genes src/fisiologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Peptídeos/metabolismo , Fosforilação , Proteínas Tirosina Quinases/metabolismo , Transdução de Sinais , Tetraspaninas/genética , Tetraspaninas/metabolismo
8.
Geriatr Nurs ; 42(5): 1042-1047, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34256154

RESUMO

This study aimed to examine the factors associated with willingness to complete advance directives (ADs) in community-dwelling older adults. In total, 121 community-dwelling older adults in Korea completed the questionnaires inquiring about their willingness and perceptions in completing ADs (susceptibility, severity, benefits, barriers, and cues to action), which were based on the Health Belief Model. The mean score for willingness to complete ADs was 6.2 (SD = 3.6). A multiple linear regression analysis showed that higher scores of perceived severity (ß = 0.199, p = 0.021), perceived benefits (ß = 0.221, p = 0.016), and cues to action (ß = 0.159, p = 0.030) were associated with a greater willingness to complete ADs. However, higher scores of perceived barriers (ß = -0.409, p < 0.001) were likely to lower the willingness to complete ADs. This study highlights that future interventions aimed at increasing AD completion rates in older adults should consider improving perceived severity, benefits, and cues to action and minimizing perceived barriers.

9.
Anim Cells Syst (Seoul) ; 25(3): 146-151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262657

RESUMO

Environmental risk factors are recognized as threats to public health. Stress granules (SGs) are non-membranous assemblies of mRNAs and proteins expressed in response to various stressors to promote cell survival. In this study, SG formation was examined to confirm the effects of polyhexamethylene guanidine phosphate (PHMG), chloromethylisothiazolinone (CMIT), and particulate matter (PM10) in airway epithelial cells, A549, HPAEpiC, and BEAS-2B cells. SGs were not observed after CMIT, PHMG, and PM10 treatments, as determined by immunofluorescence microscopy. Moreover, there was no change in the phosphorylation of the translation initiation factor eIF2αfollowing treatment with PHMG, CMIT, and PM10. Taken together, our findings might help determine the biological hazards of these materials.

10.
BMC Immunol ; 22(1): 30, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980160

RESUMO

BACKGROUND: Triggering receptor expressed on myeloid cells 2 (TREM2) signaling is considered to regulate anti-inflammatory responses in macrophages, dendritic cell maturation, osteoclast development, induction of obesity, and Alzheimer's disease pathogenesis. However, little is known regarding the effect of TREM2 on natural killer (NK) cells. RESULTS: Here, we demonstrated for the first time that CD3-CD122+NK1.1+ precursor NK (pNK) cells expressed TREM2 and their population increased in TREM2-overexpressing transgenic (TREM2-TG) mice compared with that in female C57BL/6 J wild type (WT) mice. Both NK cell-activating receptors and NK cell-associated genes were expressed at higher levels in various tissues of TREM2-TG mice than in WT mice. In addition, bone marrow-derived hematopoietic stem cells (HSCs) of TREM2-TG mice (TG-HSCs) successfully differentiated into NK cells in vitro, with a higher yield from TG-HSCs than from WT-HSCs. In contrast, TREM2 signaling inhibition by TREM2-Ig or a phosphatidylinositol 3-kinase (PI3K) inhibitor affected the expression of the NK cell receptor repertoire and decreased the expression levels of NK cell-associated genes, resulting in significant impairment of NK cell differentiation. Moreover, in melanoma-bearing WT mice, injection of bone marrow cells from TREM2-TG mice exerted greater antitumor effects than that with cells from WT control mice. CONCLUSIONS: Collectively, our data clearly showed that TREM2 promoted NK cell development and tumor regression, suggesting TREM2 as a new candidate for cancer immunotherapy.

11.
Vector Borne Zoonotic Dis ; 21(7): 502-508, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33844947

RESUMO

Coxiella burnetii is an obligate intracellular zoonotic bacterium with a global distribution. This study was conducted to investigate the prevalence of C. burnetii in different animals and to assess the potential role of these species as reservoirs of infection and transmission to humans. A total of 592 blood samples (105 beef cattle, 61 dairy cattle, 110 Korean native goats, 83 Boer goats, and 233 horses) were collected in the Republic of Korea (ROK). The C. burnetii DNA was detected from blood samples using the transposon-like repetitive region (IS1111) by PCR method. The results showed that 22.7% of the Korean-native goats, 16.4% of the dairy cattle, 15.2% of the beef cattle, 6.0% of the Boer goats, and 5.2% of the horses were positive for C. burnetii. Significant differences were found between the animal species. The univariable binary logistic regression analysis revealed that the risk of contracting C. burnetii was significantly high by 5.4-fold in Korean-native goats (95% confidence interval [CI]: 2.60%-11.27%, p = 0.000), 3.6-fold in dairy cattle (95% CI: 1.48%-8.82%, p = 0.005), and 3.3-fold in beef cattle (95% CI: 1.51%-7.28%, p = 0.003) compared with horses. A phylogenetic tree based on the IS1111 gene revealed that our sequences had 92.2%-99.9% similarity and were clustered with those detected in humans, cattle, goats, dogs, rodents, and ticks. C. burnetii circulating in the ROK exhibits genetic variation. To the best of our knowledge, this is the first study to identify C. burnetii DNA in a horse in the ROK. These results suggest that cattle, goats, and horses can be potential reservoirs for C. burnetii and play an important role in the transmission of infection. Further studies should assess the pathogenicity of C. burnetii circulating in the ROK.

12.
FASEB J ; 35(4): e21479, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33710680

RESUMO

Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell surface receptor expressed on macrophages, microglial cells, and pre-osteoclasts, and that participates in diverse cellular function, including inflammation, bone homeostasis, neurological development, and coagulation. In spite of the indispensable role of the TREM2 protein in the maintenance of immune homeostasis and osteoclast differentiation, the exact ligand for TREM2 has not yet been identified. Here, we report a putative TREM2 ligand which is secreted from MC38 cells and identified as a cyclophilin A (CypA). A specific interaction between CypA and TREM2 was shown at both protein and cellular levels. Exogenous CypA specifically interacted and co-localized with TREM2 in RAW264.7 cells, and the physical interactions were shown to regulate TREM2 signaling transduction. The Pro144 residue in the extracellular domain of TREM2 was found to be the specific binding site of CypA. When considered together, this provides evidence that CypA interacts specifically with TREM2 as a potent ligand.


Assuntos
Ciclofilina A/metabolismo , Ligantes , Microglia/metabolismo , Células Mieloides/metabolismo , Animais , Proteínas de Transporte/metabolismo , Células Cultivadas , Humanos , Macrófagos/metabolismo , Osteoclastos/metabolismo
13.
Food Sci Nutr ; 9(2): 1232-1239, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33598207

RESUMO

Cheese contains various beneficial nutrients, including calcium and whey protein, as well as large amounts of saturated fatty acids. Thus, intake of cheese increases the production of low-density lipoprotein-cholesterol (LDL-C), a well-defined risk factor for cardiovascular disease. Therefore, identification of natural products that inhibit LDL-C production following cheese intake and verification of the efficacy of such products in animal models are essential. Here, we evaluated the effects of Allium hookeri, a well-known traditional herbal remedy, on metabolism and thermogenesis in mice consuming a cheese-containing diet. Intake of A. hookeri extracts significantly blocked increases in body weight and fat mass caused by intake of Gouda cheese in mice. Additionally, increases in blood triglyceride levels following intake of Gouda cheese were alleviated by A. hookeri. Moreover, intake of Gouda cheese enhanced thermogenesis efficiency. Thus, A. hookeri may have applications as an important additive for reducing the risk of metabolic disease resulting from cheese consumption.

14.
Chonnam Med J ; 57(1): 27-35, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33537216

RESUMO

Liposomes, with their flexible physicochemical and biophysical properties, continue to be studied as an important potential a critical drug delivery system. Liposomes have overcome the challenges of conventional free drug therapy by encapsulating therapeutic agents, thereby improving in vivo biodistribution and reducing systemic toxicity. New imaging modalities and interpretation techniques, as well as new techniques for targetable system formulation technique, and tumor environmental information, have affected the search for a means of overcoming the difficulties of conventional liposome formulation. In this review, we briefly discuss how liposomal formulation has been applied across the biomedical field, particularly as a therapy, and the role it may play in the future, when paired with new developments in diagnosis and theranostics. The biological challenges that still remain and the translational obstacles are discussed.

15.
FASEB J ; 35(3): e21369, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33554392

RESUMO

Transmembrane 4 L six family member 5 (TM4SF5) translocates intracellularly and promotes cell migration, but how subcellular TM4SF5 traffic is regulated to guide cellular migration is unknown. We investigated the influences of the extracellular environment and intracellular signaling on the TM4SF5 traffic with regard to migration directionality. Cell adhesion to fibronectin (FN) but not poly-l-lysine enhanced the traffic velocity and straightness of the TM4SF5WT (but not palmitoylation-deficient mutant TM4SF5 Pal - ) toward the leading edges, depending on tubulin acetylation. Acetylated-microtubules in SLAC2B-positive cells reached mostly the juxtanuclear regions, but reached-out toward the leading edges upon SLAC2B suppression. TM4SF5 expression caused SLAC2B not to be localized at the leading edges. TM4SF5 colocalization with HDAC6 depended on paxillin expression. The trimeric complex consisting of TM4SF5, HDAC6, and SLAC2B might, thus, be enriched at the perinuclear cytosols toward the leading edges. More TM4SF5WT translocation to the leading edges was possible when acetylated-microtubules reached the frontal edges following HDAC6 inhibition by paxillin presumably at new cell-FN adhesions, leading to persistent cell migration. Collectively, this study revealed that cell-FN adhesion and microtubule acetylation could control intracellular traffic of TM4SF5 vesicles to the leading edges via coordinated actions of paxillin, SLAC2B, and HDAC6, leading to TM4SF5-dependent cell migration.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Membrana Celular/metabolismo , Matriz Extracelular/fisiologia , Proteínas de Membrana/metabolismo , Microtúbulos/metabolismo , Acetilação , Adesão Celular , Movimento Celular , Fibronectinas/fisiologia , Células Hep G2 , Desacetilase 6 de Histona/fisiologia , Humanos , Paxilina/fisiologia , Transporte Proteico
16.
Biomater Sci ; 9(5): 1639-1651, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33432951

RESUMO

Developing a cutting-edge system capable of ensuring long-lasting functionality of therapeutic agents and implementing diverse delivery modes is challenging. A quasi-spherical triple-layered capsule containing suspended liquid droplets and allowing multi-modal delivery of therapeutic agents in the aqueous phase was developed, primarily by adopting the core principles for creating liquid marbles. A naturally derived wettable polysaccharide-pectin-was utilized as a liquid-air interfacial barrier to keep the liquid droplets in the core zone. To tailor the pectin-coated droplet as a therapeutic agent carrier, anionic alginate and cationic chitosan layers were sequentially formed via additional interactions: physically stacking substances with structural chirality (pectin-alginate) and inducing electrostatic association to create the reversible complex coacervates (alginate-chitosan). The resulting system, which is called a Chitosan-Alginate-Pectin-coated Suspended-Liquid-Encapsulating (CAPSuLE) marble, had sufficient mechanical strength to resist external harsh environments and exhibited unique features: ecofriendly sustainability, responsiveness to external stimuli, coacervate-driven coalescence for linking adjacent marbles, and a self-repairing ability. The proposed CAPSuLE system can facilitate the adoption of the liquid-marble concept to biomedical fields, extending its applicability in the fields of biology and applied engineering.


Assuntos
Quitosana , Pectinas , Alginatos , Carbonato de Cálcio , Eletricidade Estática
17.
Mol Biol Rep ; 48(1): 97-104, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33433834

RESUMO

Semisulcospira gottschei is an Asian endemic species inhabiting Korea and China. However, genetic structure analysis of the resource management of this species has not been performed. To investigate the genetic diversity among populations, microsatellites can be used to determine the geographic origins of marine and freshwater species. This study investigated the genetic structures of the Korean and Chinese populations of S. gottschei based on mitochondrial DNA (mtDNA) Cytochrome oxidase subunit I (COI) and polymorphic microsatellite loci developed from Semisulcospira coreana. Analysis of the mtDNA COI sequence revealed 43 haplotypes, which indicated no gene flow between the Korean and Chinese populations. To further elucidate the genetic structures of the Korean and Chinese populations, the population genetics of S. gottschei were analyzed using nine microsatellite markers. The genetic diversity analysis showed an average of 5.25 alleles per locus, with an average allelic richness of 4.02. Excessive homozygosity was found at all loci, which was expected to be due to the presence of null alleles at all loci. Populations of S. gottschei formed two separate clusters according to pairwise FST and AMOVA. Also, the UPGMA tree, PCA, STRUCTURE, and GeneClass indicated separation of the 11 populations into two clusters: Korea and China. These results have potential use in the management, restoration, and distinction of the origin country of populations.


Assuntos
DNA Mitocondrial/genética , Gastrópodes/genética , Genética Populacional , Alelos , Animais , Fluxo Gênico , Variação Genética , Haplótipos , Repetições de Microssatélites/genética , Filogenia
18.
Explore (NY) ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33516616

RESUMO

Central facial palsy, which is a sequela of stroke, is associated with decreased quality of life and psychosocial function. Integrative Korean medicine management, including acupuncture and Chuna-manual therapy, has been used to treat neurological diseases, including facial palsy. We report three cases of central facial palsy patients who had these symptoms over three months after a stroke. They had received rehabilitation treatment for the paralyzed upper and lower extremities. However, as their central facial palsy symptom did not improve, Chuna-manual therapy (SJS nonresistance technique) for facial palsy was started along with acupuncture. Oral region movement improved after four weeks of integrative acupuncture and Chuna-manual therapy. After ten to sixteen weeks of treatment, the facial nerve grading system 2.0 grades improved by one in two cases. In one case, although there was no significant change in the grade, she was satisfied with the results after adding Chuna-manual therapy to acupuncture. There were no adverse events. Integrative management, including acupuncture and Chuna-manual therapy, might be an effective treatment strategy for central facial palsy. Further prospective, controlled studies are warranted.

19.
J Pathol ; 253(1): 55-67, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32918742

RESUMO

Nonalcoholic fatty liver disease is a chronic condition involving steatosis, steatohepatitis and fibrosis, and its progression remains unclear. Although the tetraspanin transmembrane 4 L six family member 5 (TM4SF5) is involved in hepatic fibrosis and cancer, its role in nonalcoholic steatohepatitis (NASH) progression is unknown. We investigated the contribution of TM4SF5 to liver pathology using transgenic and KO mice, diet- or drug-treated mice, in vitro primary cells, and in human tissue. TM4SF5-overexpressing mice exhibited nonalcoholic steatosis and NASH in an age-dependent manner. Initially, TM4SF5-positive hepatocytes and liver tissue exhibited lipid accumulation, decreased Sirtuin 1 (SIRT1), increased sterol regulatory-element binding proteins (SREBPs) and inactive STAT3 via suppressor of cytokine signaling (SOCS)1/3 upregulation. In older mice, TM4SF5 promoted inflammatory factor induction, SIRT1 expression and STAT3 activity, but did not change SOCS or SREBP levels, leading to active STAT3-mediated ECM production for NASH progression. A TM4SF5-associated increase in chemokines promoted SIRT1 expression and progression to NASH with fibrosis. Suppression of the chemokine CCL20 reduced immune cell infiltration and ECM production. Liver tissue from high-fat diet- or CCl4 -treated mice and human patients exhibited TM4SF5-dependent steatotic or steatohepatitic livers with links between TM4SF5-mediated SIRT1 modulation and SREBP or SOCS/STAT3 signaling axes. TM4SF5-mediated STAT3 activation in fibrotic NASH livers increased collagen I and laminin γ2. Both collagen I α1 and laminin γ2 suppression resulted in reduced SIRT1 and active STAT3, but no change in SREBP1 or SOCS, and abolished CCl4 -mediated mouse liver damage. TM4SF5-mediated signaling pathways that involve SIRT1, SREBPs and SOCS/STAT3 promoted progression to NASH. Therefore, TM4SF5 and its downstream effectors may be promising therapeutic targets to treat nonalcoholic fatty liver disease. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Matriz Extracelular/enzimologia , Metabolismo dos Lipídeos , Cirrose Hepática Experimental/enzimologia , Fígado/enzimologia , Proteínas de Membrana/metabolismo , Hepatopatia Gordurosa não Alcoólica/enzimologia , Sirtuína 1/metabolismo , Animais , Tetracloreto de Carbono , Linhagem Celular Tumoral , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Dieta Hiperlipídica , Progressão da Doença , Matriz Extracelular/patologia , Humanos , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/genética , Cirrose Hepática Experimental/patologia , Proteínas de Membrana/genética , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Transdução de Sinais
20.
Lasers Med Sci ; 36(1): 99-109, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32363436

RESUMO

We have previously reported the protective effects of blue light-emitting diode (BLED)-stimulated cell metabolites on cell injury. To further examine the effect of conditioned media (CM) derived from BLED (5 J/cm2)-exposed human normal fibroblasts (CMBL5) for clinical application, we have used the choline chloride and phenol red-free media and then concentrated CMBL5 using a centrifugal filter unit. The collected CMBL5-lower part (CMBL5-LO) has evaluated the inflammatory protein expression profile in LPS-stimulated RAW264.7 cells. Comprehensive metabolomic profiling of CMBL5-LO was carried out using hybrid tandem mass spectrometry. Treatment with CMBL5-LO showed the cytoprotective effect on apoptotic cell death, but rather increased apoptotic cells after treatment with CMBL5-upper part (CMBL5-UP). In addition, CMBL5-LO inhibited several chemo-attractants, including interleukin (IL)-6, macrophage inflammatory protein (MIP)-2, chemokine (C-C motif) ligand 5 (CCL5), granulocyte colony-stimulating factor (GCSF), and monocyte chemoattractant protein-1 (MCP-1) expression. Pro-inflammatory nitric oxide was decreased after CMBL5-LO treatment, but not by CMBL5-UP treatment. Interestingly, treatment with CMBL5-LO stimulated expression of heme oxygenase-1, indicating its anti-inflammatory property. Most endoplasmic reticulum (ER) stress proteins except for transcription factor C/EBP homologous protein (CHOP) were highly expressed after irradiation with BLED in cells. Further studies are needed to examine the precise mechanism by CMBL5-LO in cells.


Assuntos
Anti-Inflamatórios/farmacologia , Meios de Cultivo Condicionados/farmacologia , Fibroblastos/efeitos da radiação , Luz , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Quimiocina CXCL2/metabolismo , Cor , Citocinas/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Óxido Nítrico/biossíntese , Substâncias Protetoras/farmacologia , Células RAW 264.7 , Regulação para Cima/efeitos dos fármacos
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