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1.
J Acupunct Meridian Stud ; 15(4): 264-272, 2022 Aug 31.
Article in English | MEDLINE | ID: mdl-36521775

ABSTRACT

Lumbosacral radiculopathy (LR) is a musculoskeletal disorder or pain syndrome that is generally linked to the compression or irritation of the nerve root. There is a growing interest in the development of efficient acupuncture-based treatments for LR comparable to western medicine. Structured traditional Korean medical treatments including intensified acupuncture stimulus on the EX-B2 point using the G-shaped posture modified from the sitting posture were applied to four LR patients, and the outcomes were evaluated based on objective clinical endpoints including a numeric rating scale (NRS), the Oswestry disability index (ODI), the manual muscle test (MMT), neurological symptoms, and plantar photography. Patients showed improvements in NRS, ODI, MMT, and neurological symptoms without adverse effects during hospitalization and follow-up visits. Moreover, we observed substantial dissolvement of hyperkeratinization and parchedness of the soles of the feet, which was not reported previously. These four cases demonstrate the clinical usefulness of traditional medicine and the diagnostic applicability of plantar photography. However, further randomized controlled trials are required to confirm our findings.


Subject(s)
Acupuncture Therapy , Radiculopathy , Humans , Radiculopathy/therapy , Radiculopathy/diagnosis , Pain Management , Treatment Outcome
2.
J Med Chem ; 64(21): 15912-15935, 2021 11 11.
Article in English | MEDLINE | ID: mdl-34662122

ABSTRACT

Due to the increased morbidity and mortality by fungal infections and the emergence of severe antifungal resistance, there is an urgent need for new antifungal agents. Here, we screened for antifungal activity in our in-house library through the minimum inhibitory concentration test and derived two hit compounds with moderate antifungal activities. The hit compounds' antifungal activities and drug-like properties were optimized by substituting various aryl ring, alkyl chain, and methyl groups. Among the optimized compounds, 22h was the most promising candidate with good drug-like properties and exhibited potent fast-acting fungicidal antifungal effects against various fungal pathogens and synergistic antifungal activities with some known antifungal drugs. Additionally, 22h was further confirmed to disturb fungal cell wall integrity by activating multiple cell wall integrity pathways. Furthermore, 22h exerted significant antifungal efficacy in both the subcutaneous infection mouse model and ex vivo human nail infection model.


Subject(s)
Antifungal Agents/therapeutic use , Fungi/drug effects , Mycoses/drug therapy , Animals , Antifungal Agents/pharmacokinetics , Antifungal Agents/pharmacology , Antifungal Agents/toxicity , Cell Wall/drug effects , Drug Evaluation, Preclinical , Drug Synergism , Female , Humans , Male , Mice , Microbial Sensitivity Tests , Mycoses/microbiology , Rats, Sprague-Dawley
3.
Neuron ; 108(4): 691-706.e10, 2020 11 25.
Article in English | MEDLINE | ID: mdl-32905785

ABSTRACT

Sensory discrimination is essential for survival. However, how sensory information is finely controlled in the brain is not well defined. Here, we show that astrocytes control tactile acuity via tonic inhibition in the thalamus. Mechanistically, diamine oxidase (DAO) and the subsequent aldehyde dehydrogenase 1a1 (Aldh1a1) convert putrescine into GABA, which is released via Best1. The GABA from astrocytes inhibits synaptically evoked firing at the lemniscal synapses to fine-tune the dynamic range of the stimulation-response relationship, the precision of spike timing, and tactile discrimination. Our findings reveal a novel role of astrocytes in the control of sensory acuity through tonic GABA release.


Subject(s)
Astrocytes/physiology , Neural Inhibition/physiology , Thalamus/physiology , Touch Perception/physiology , gamma-Aminobutyric Acid/physiology , Aldehyde Dehydrogenase 1 Family/metabolism , Amine Oxidase (Copper-Containing)/metabolism , Animals , Astrocytes/metabolism , Astrocytes/ultrastructure , Bestrophins/biosynthesis , Bestrophins/genetics , Female , GABA Antagonists , Immunohistochemistry , Inhibitory Postsynaptic Potentials/physiology , Macrolides/pharmacology , Male , Mice , Mice, Knockout , Microscopy, Electron , Neurons/metabolism , Neurons/physiology , Patch-Clamp Techniques , Picrotoxin/pharmacology , Primary Cell Culture , Pyridazines/pharmacology , RNA, Small Interfering/pharmacology , Retinal Dehydrogenase/metabolism , gamma-Aminobutyric Acid/biosynthesis , gamma-Aminobutyric Acid/pharmacology
4.
Am J Chin Med ; 48(4): 987-1003, 2020.
Article in English | MEDLINE | ID: mdl-32431181

ABSTRACT

Our previous report revealed that Gardenia jasminoides (GJ) has protective effects against acute pancreatitis. So, we examined whether aqueous extract of GJ has anti-inflammation and antifibrotic effects even against cerulein-induced chronic pancreatitis (CP). CP was induced in mice by an intraperitoneal injection of a stable cholecystokinin (CCK) analogue, cerulein, six times a day, four days per week for three weeks. GJ extract (0.1 or 1[Formula: see text]g/kg) or saline (control group) were intraperitoneally injected 1[Formula: see text]h before first cerulein injection. After three weeks of stimulation, the pancreas was harvested for the examination of several fibrotic parameters. In addition, pancreatic stellate cells (PSCs) were isolated using gradient methods to examine the antifibrogenic effects of GJ. In the cerulein-induced CP mice, the histological features of the pancreas showed severe tissue damage such as enlarged interstitial spaces, inflammatory cell infiltrate and glandular atrophy, and tissue fibrosis. However, treatment of GJ reduced the severity of CP such as pancreatic edema and inflammatory cell infiltration. Furthermore, treatment of GJ increased pancreatic acinar cell survival, and reduced pancreatic fibrosis and activation of PSC in vivo and in vitro. In addition, GJ treatment inhibited the activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) in the PSCs. These results suggest that GJ attenuated the severity of CP and the pancreatic fibrosis by inhibiting JNK and ERK activation during CP.


Subject(s)
Ceruletide/adverse effects , Gardenia/chemistry , Pancreatitis, Chronic/drug therapy , Pancreatitis, Chronic/prevention & control , Phytotherapy , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Animals , Disease Models, Animal , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Fibrosis , Injections, Intraperitoneal , JNK Mitogen-Activated Protein Kinases/metabolism , Male , Mice, Inbred C57BL , Pancreas/pathology , Pancreatic Stellate Cells/pathology , Pancreatitis, Chronic/chemically induced , Pancreatitis, Chronic/pathology , Plant Extracts/isolation & purification
5.
J Microbiol Biotechnol ; 28(6): 860-873, 2018 Jun 28.
Article in English | MEDLINE | ID: mdl-29642293

ABSTRACT

Although ginseng marc is a by-product obtained during manufacturing of various commercial ginseng products and has been routinely discarded as a waste, it still contains considerable amounts of potential bioactive compounds, including saponins and polysaccharides. Previously, we reported that ginseng oligosaccharides derived from ginseng marc polysaccharides by enzymatic hydrolysis exert immunostimulatory activities in macrophages and these activated macrophages are in turn able to inhibit the growth of skin melanoma cells by inducing apoptosis. In the present study, a more detailed investigation of the immunostimulatory activity and underlying action mechanisms of an enzymatic hydrolysate (GEH) containing these oligosaccharides derived from ginseng marc polysaccharides was performed. The levels of proinflammatory cytokines and anti-inflammatory cytokines were measured in GEH-stimulated RAW264.7 macrophages using RT-PCR analysis and ELISA. The expression levels of Toll-like receptor 2 (TLR2) and TLR4, Dectin-1, and MerTK were measured by RT-PCR analysis or western blot analysis, and the phagocytic activities of GEH-challenged bone marrow-derived macrophages toward apoptotic Jurkat cells were assayed using fluorescence microscopy. GEH induced the production of both proinflammatory cytokines TNF-α and IL-6, and anti-inflammatory cytokine IL-10 in RAW 264.7 cells. The expression of the TLR2 and MerTK mRNAs was increased upon GEH treatment. Phagocytosis of apoptotic Jurkat cells was enhanced in GEH-treated macrophages. Based on the results, this enzymatic hydrolysate (GEH) containing oligosaccharides exerts immunostimulatory effects by maintaining the balance between M1 and M2 cytokines, facilitating macrophage activation and contributing to the efficient phagocytosis of apoptotic cells. Therefore, the GEH could be developed as value-added, health-beneficial food materials with immunostimulatory effects.


Subject(s)
Immunologic Factors/metabolism , Macrophages/drug effects , Macrophages/immunology , Oligosaccharides/metabolism , Panax/chemistry , Protein-Tyrosine Kinases/metabolism , Toll-Like Receptor 2/metabolism , Animals , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Humans , Immunologic Factors/isolation & purification , Mice , Oligosaccharides/isolation & purification , Plant Extracts/isolation & purification , Plant Extracts/metabolism , Real-Time Polymerase Chain Reaction
6.
PLoS One ; 13(1): e0190711, 2018.
Article in English | MEDLINE | ID: mdl-29309435

ABSTRACT

Postoperative ileus (POI) is an important factor prolonging the length of hospital stay following colorectal surgery. We retrospectively explored whether there is a clinically relevant association between intraoperative hypothermia and POI in patients who underwent laparoscopic colorectal surgery for malignancy within the setting of an enhanced recovery after surgery (ERAS) program between April 2016 and January 2017 at our institution. In total, 637 patients were analyzed, of whom 122 (19.2%) developed clinically and radiologically diagnosed POI. Overall, 530 (83.2%) patients experienced intraoperative hypothermia. Although the mean lowest core temperature was lower in patients with POI than those without POI (35.3 ± 0.5°C vs. 35.5 ± 0.5°C, P = 0.004), the independence of intraoperative hypothermia was not confirmed based on multivariate logistic regression analysis. In addition to three variables (high age-adjusted Charlson comorbidity index score, long duration of surgery, high maximum pain score during the first 3 days postoperatively), cumulative dose of rescue opioids used during the first 3 days postoperatively was identified as an independent risk factor of POI (odds ratio = 1.027 for each 1-morphine equivalent [mg] increase, 95% confidence interval = 1.014-1.040, P <0.001). Patients with hypothermia showed significant delays in both progression to a soft diet and discharge from hospital. In conclusion, intraoperative hypothermia was not independently associated with POI within an ERAS pathway, in which items other than thermal measures might offset its negative impact on POI. However, as it was associated with delayed discharge from the hospital, intraoperative maintenance of normothermia is still needed.


Subject(s)
Colorectal Neoplasms/therapy , Hyperthermia, Induced , Ileus/etiology , Intraoperative Care , Laparoscopy/adverse effects , Postoperative Complications , Colorectal Neoplasms/surgery , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Retrospective Studies
7.
Carbohydr Polym ; 146: 187-96, 2016 08 01.
Article in English | MEDLINE | ID: mdl-27112865

ABSTRACT

A water-soluble polysaccharide JS-MP-1 was isolated from Korean mulberry fruits Oddi (Morus alba L.). Sugar linkage analysis and NMR data confirmed that it is a rhamnogalacturonan type I (RG I) polymer carrying arabinan and arabinogalactan (AG II) side chains. JS-MP-1 reduced dose-dependently the viability of 3T3-L1 pre-adipocyte cells, significantly stimulated the cleavage of caspases 9 and 3 and poly (ADP-ribose) polymerase (PARP) and decreased the ratio of Bcl-2 to Bax expression level that led to mitochondrial dysfunction and apoptosis in pre-adipocyte cells. The apoptotic death was mediated by stimulation of MAPKs (ERK and p38) signalling pathway. These results suggest that JS-MP-1 is able to reduce the number of fat cells and the mass of adipose tissue via inhibition of pre-adipocyte proliferation and thus JS-MP-1 itself or a crude aqueous Oddi extract containing this polysaccharide can be used as functional ingredient of health-beneficial food supplements for the treatment or prevention of obesity disorders.


Subject(s)
Apoptosis/drug effects , Morus/chemistry , Pectins/isolation & purification , Polysaccharides/isolation & purification , Polysaccharides/pharmacology , 3T3 Cells , 3T3-L1 Cells , Adipocytes/cytology , Adipocytes/drug effects , Animals , Anti-Obesity Agents/chemistry , Anti-Obesity Agents/isolation & purification , Cell Proliferation/drug effects , Enzyme Activation/drug effects , Fruit/chemistry , Gene Expression Regulation, Enzymologic/drug effects , Mice , Mitogen-Activated Protein Kinases/metabolism , Obesity/drug therapy
8.
Pain Pract ; 16(8): 1019-1026, 2016 Nov.
Article in English | MEDLINE | ID: mdl-26443389

ABSTRACT

INTRODUCTION: This randomized, double-blind study compared the efficacy of hyaluronidase co-injection with that of local anesthesia alone on the degree of pain and quality of life in patients with myofascial pain syndrome (MPS). METHODS: Sixty-one adults, aged 25 to 75 years, with MPS affecting both trapezius muscles were randomly assigned to one of the 2 treatment groups: lidocaine (group L: n = 31) or hyaluronidase (group H: n = 30). All patients received Trigger point injection (TPI). Group L received 3.2 mL 0.5% lidocaine alone. Group H received the same solution of lidocaine mixed with hyaluronidase (600 iu/mL). Patients were followed for 14 days (pre- and post-TPI days 0, 1, 4, 7, and 14) with the verbal numerical rating scale (VNRS), and the primary outcome was VNRS on day 7. Also, we evaluated the neck disability index (NDI) and the short form of brief pain inventory (BPI-SF) on pre- and post-TPI day 14. RESULTS: In both groups, VNRS decreased on days 4, 7, and 14 compared to the pre-TPI. However, in group H, VNRS decreased on day 1 also. There were no significant differences of VNRS between the 2 groups during 14 days. NDI and BPI-SF scores also significantly decreased after TPI in both groups. CONCLUSIONS: There were no significant differences between groups in terms of VNRS, NDI, or BPI-SF scores. However, TPI consisting of lidocaine mixed with hyaluronidase worked more effectively than lidocaine alone on post-TPI day 1. Further, hyaluronidase showed a tendency to reduce TPI-related soreness.

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