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The therapeutic efficacy of adipose mesenchymal stem cells (Ad-MSCs) for acute kidney injury (AKI) has been investigated extensively, and the anti-apoptotic, anti-inflammatory, and proangiogenic effects of heme oxygenase-1 (HO-1) reportedly ameliorate AKI. We hypothesized that the therapeutic efficacy of Ad-MSCs is dependent on their expression level of HO-1. The viability and migration ability of cisplatin-treated human renal proximal tubular epithelial cells were assessed. Sprague–Dawley rats were divided into control, cisplatin (10 mg/kg), and cisplatin plus Ad MSCs (with high and low HO-1 expression) groups. The HO-1 expression level in hAd-MSCs increased with increasing passage number, peaking at passage 4 and decreasing thereafter. The viability and migratory ability of hAd-MSCs with high HO-1 expression were greater than those of hAd-MSCs with low HO-1 expression. Renal tubular toxicity in cisplatin-treated rats was ameliorated by administration of hAd-MSCs with high HO-1 expression, although the levels of blood urea nitrogen and serum creatinine did not differ according to the level of HO-1 expression. The magnitude of reactive oxygen species induced DNA damage was lower in hAd-MSCs with high HO-1 expression than in those with low HO-1 expression. Administration of hAd-MSCs significantly suppressed cisplatin induced apoptosis. Also, hAd-MSCs with high HO-1 expression were more resistant to cisplatin-induced apoptosis than were those with low HO-1 expression. hAd MSCs with high HO-1 expression have therapeutic potential for cisplatin induced nephrotoxicity, based on our in vitro and in vivo results. These findings will facilitate the development of novel therapeutic strategies for cisplatin-induced AKI. [ABSTRACT FROM AUTHOR]

The therapeutic efficacy of adipose mesenchymal stem cells (Ad-MSCs) for acute kidney injury (AKI) has been investigated extensively, and the anti-apoptotic, anti-inflammatory, and proangiogenic effects of heme oxygenase-1 (HO-1) reportedly ameliorate AKI. We hypothesized that the therapeutic efficacy of Ad-MSCs is dependent on their expression level of HO-1. The viability and migration ability of cisplatin-treated human renal proximal tubular epithelial cells were assessed. Sprague–Dawley rats were divided into control, cisplatin (10 mg/kg), and cisplatin plus Ad MSCs (with high and low HO-1 expression) groups. The HO-1 expression level in hAd-MSCs increased with increasing passage number, peaking at passage 4 and decreasing thereafter. The viability and migratory ability of hAd-MSCs with high HO-1 expression were greater than those of hAd-MSCs with low HO-1 expression. Renal tubular toxicity in cisplatin-treated rats was ameliorated by administration of hAd-MSCs with high HO-1 expression, although the levels of blood urea nitrogen and serum creatinine did not differ according to the level of HO-1 expression. The magnitude of reactive oxygen species induced DNA damage was lower in hAd-MSCs with high HO-1 expression than in those with low HO-1 expression. Administration of hAd-MSCs significantly suppressed cisplatin induced apoptosis. Also, hAd-MSCs with high HO-1 expression were more resistant to cisplatin-induced apoptosis than were those with low HO-1 expression. hAd MSCs with high HO-1 expression have therapeutic potential for cisplatin induced nephrotoxicity, based on our in vitro and in vivo results. These findings will facilitate the development of novel therapeutic strategies for cisplatin-induced AKI. [ABSTRACT FROM AUTHOR]

The role of psoralen (PS), a major active component extracted from Psoralea corylifolia L. seed, in renal fibrosis is still unclear. Thus, the objective of this study was to evaluate the effects of PS on the development and progression of renal fibrosis induced by unilateral ureteral obstruction (UUO) in a mouse model. Mice were divided into four groups: PS (20 mg/kg, i.g., n = 5), PS + sham (n = 5), UUO (n = 10), and PS + UUO (n = 10). PS was intragastrically administered 24 h before UUO and continued afterwards for 7 days. All mice were killed 7 days post UUO. Severe tubular atrophy, tubular injury, and tubulointerstitial fibrosis (TIF) were significantly developed in UUO mice. A higher expression of transforming growth factor-β1 (TGF-β1) was accompanied by elevated levels of α-smooth muscle actin (α-SMA) and phosphorylated Smad2/3 (pSmad2/3) at 7 days post UUO. However, PS treatment reduced tubular injury, interstitial fibrosis, and the expression levels of TGF-β1, α-SMA, and pSmad2/3. Furthermore, the levels of macrophages (represented by F4/80 positive cells) and the inflammasome, reflected by inflammasome markers such as nucleotide-binding and oligomerization domain-like receptors protein 3 (NLRP3) and cleaved caspase1 (cCASP-1), were significantly decreased by PS treatment. These results suggest that PS merits further exploration as a therapeutic agent in the management of chronic kidney disease (CKD). [ABSTRACT FROM AUTHOR]

Epidemiological investigations have suggested that serum 25-hydroxyvitamin D [25(OH)D] level has significantly inverse associations with various neurological and neurodegenerative diseases. However, little is known about 25(OH)D level in human cerebrospinal fluid (CSF). Thus, the aim of this study was to determine correlations of 25(OH)D level in CSF with serum total, bioavailable, and free 25(OH)D levels. This observational study enrolled a total of 117 subjects (58 patients with non-neurologic disease and 59 patients with neurologic disease) from 2017 to 2018. CSF and blood samples were collected in pairs. Total 25(OH)D levels in CSF and serum and vitamin D binding protein (VDBP) levels in serum were measured. We also performed GC genotyping for polymorphisms of rs4588 and rs7041 to calculate bioavailable and free 25(OH)D levels. CSF total 25(OH)D levels were compared with serum total, bioavailable, and free 25(OH)D levels. Mean total 25(OH)D concentrations in CSF and serum of all patients were 37.14 ± 7.71 and 25.72 ± 12.37 ng/mL, respectively. The mean total 25(OH)D concentration in CSF was generally 1.4-fold higher than that in the serum. Total 25(OH)D concentrations in CSF showed weakly positive but significant correlations with serum total, bioavailable, and free 25(OH)D concentrations (P = 0.022, P = 0.033, and P = 0.026, respectively). Serum total 25(OH)D concentration was also correlated with serum VDBP concentration (P = 0.017). However, total 25(OH)D levels in CSF of non-neurologic disease group and neurologic disease group were similar. Total 25(OH)D level in CSF has weakly positive but significant correlations with serum total, bioavailable, and free 25-hydroxy vitamin D levels in the Korean population. The distribution of CSF total 25(OH)D in Korean neurologic and non-neurologic disease patients was presented. [ABSTRACT FROM AUTHOR]

Background. Bioavailable 25-hydroxy vitamin D (25(OH)D) has been suggested for the accurate determination of vitamin D status. The purpose of this study was to determine the utility of bioavailable 25(OH)D in assessing vitamin D status when vitamin D-binding protein (VDBP) was significantly altered by pregnancy and liver cirrhosis (LC). The role of genotyping of GC, a gene encoding VDBP, in the determination of bioavailable 25(OH)D concentration in a Korean population was also evaluated. Methods. This prospective study enrolled a total of 136 subjects (53 healthy controls, 45 patients with LC, and 38 pregnant women) from 2017 to 2018. The concentrations of total 25(OH)D and VDBP were measured, and bioavailable 25(OH)D concentrations were calculated. GC genotyping was performed to determine rs4588 and rs7041 polymorphisms. Clinical and laboratory data were compared among the three groups of subjects. Results. Median VDBP and total 25(OH)D concentrations were 165.2 μg/ml and 18.5 ng/ml in healthy controls, 76.9 μg/ml and 10.5 ng/ml in patients with LC, and 368.9 μg/ml and 17.7 ng/ml in pregnant women, respectively. Compared with controls, patients diagnosed with LC had significantly lower VDBP and total 25(OH)D concentrations (all P<0.001) while pregnant women had significantly higher VDBP concentrations (P<0.001). Although total 25(OH)D concentrations in pregnant women were similar to those in controls (P=0.394), their bioavailable 25(OH)D concentrations were significantly lower (1.2 vs. 3.0 ng/ml; P<0.001). Among all the three groups combined, the genotype-specific bioavailable 25(OH)D and the genotype-independent bioavailable 25(OH)D concentrations did not differ significantly (P=0.299). Conclusions. Our study has demonstrated that bioavailable 25(OH)D concentration reflects vitamin D status more accurately than the total 25(OH)D concentration, especially in pregnant women. In addition, GC genotyping did not significantly affect bioavailable 25(OH)D concentration. Therefore, if VDBP concentration is significantly altered, the measurement of bioavailable 25(OH)D concentration might facilitate the accurate determination of vitamin D status. However, GC genotyping might be unnecessary. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor-delta (PPAR-δ)-dependent signaling is associated with rapid wound healing in the skin. Here, we investigated the therapeutic effects of PPAR-δ-agonist treatment on cardiac healing in post-myocardial infarction (MI) rats. Animals were assigned to the following groups: sham-operated control group, left anterior descending coronary artery ligation (MI) group, or MI with administration of the PPAR-δ agonist GW610742 group. GW610742 (1 mg/kg) was administrated intraperitoneally after the operation and repeated every 3 days. Echocardiographic data showed no differences between the two groups in terms of cardiac function and remodeling until 4 weeks. However, the degrees of angiogenesis and fibrosis after MI were significantly higher in the GW610742-treated rats than in the untreated MI rats at 1 week following MI, which changes were not different at 2 weeks after MI. Naturally, PPAR-δ expression in infarcted myocardium was highest increased in 3 day after MI and then disappeared in 14 day after MI. GW610742 increased myofibroblast differentiation and transforming growth factor-beta 2 expression in the infarct zone at 7 days after MI. GW610742 also increased bone marrow-derived mesenchymal stem cell (MSC) recruitment in whole myocardium, and increased serum platelet-derived growth factor B, stromal-derived factor-1 alpha, and matrix metallopeptidase 9 levels at day 3 after MI. PPAR-δ agonists treatment have the temporal effect on early fibrosis of infarcted myocardium, which might not sustain the functional and structural beneficial effect. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and progression to chronic kidney disease (CKD). However, no effective therapeutic intervention has been established for ischemic AKI. Endothelial progenitor cells (EPCs) have major roles in the maintenance of vascular integrity and the repair of endothelial damage; they also serve as therapeutic agents in various kidney diseases. Thus, we examined whether EPCs have a renoprotective effect in an IRI mouse model. Mice were assigned to sham, EPC, IRI-only, and EPC-treated IRI groups. EPCs originating from human peripheral blood were cultured. The EPCs were administered 5 min before reperfusion, and all mice were killed 72 h after IRI. Blood urea nitrogen, serum creatinine, and tissue injury were significantly increased in IRI mice; EPCs significantly improved the manifestations of IRI. Apoptotic cell death and oxidative stress were significantly reduced in EPC-treated IRI mice. Administration of EPCs decreased the expression levels of NLRP3, cleaved caspase-1, p-NF-κB, and p-p38. Furthermore, the expression levels of F4/80, ICAM-1, RORγt, and IL-17RA were significantly reduced in EPC-treated IRI mice. Finally, the levels of EMT-associated factors (TGF-β, α-SMA, Snail, and Twist) were significantly reduced in EPC-treated IRI mice. This study shows that inflammasome-mediated inflammation accompanied by immune modulation and fibrosis is a potential target of EPCs as a treatment for IRI-induced AKI and the prevention of progression to CKD. [ABSTRACT FROM AUTHOR]

The immunologic aspects of radiation pneumonitis (RP) are unclear. We analyzed variations in cytokine profiles between patients with grade (Gr) 0–1 and Gr ≥ 2 RP. Fifteen patients undergoing concurrent chemoradiotherapy for non-small cell lung cancer were included. Blood samples of 9 patients with Gr 0–1 and 6 with Gr ≥ 2 RP were obtained from the Biobank. Cytokine levels were evaluated using an enzyme linked immunosorbent assay at before radiotherapy (RT) initiation, 1, 3, and 6 weeks post-RT initiation, and 1 month post-RT completion. Concentrations of granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β were analyzed; none were related to the occurrence of Gr ≥ 2 RP at pre-RT initiation. At 3 weeks, relative changes in the G-CSF, IL-6, and IFN-γ levels differed significantly between the groups (p = 0.026, 0.05 and 0.026, respectively). One month post-RT completion, relative changes of IL-17 showed significant differences (p = 0.045); however, relative changes in TNF-α, IL-10, IL-13, and TGF-β, did not differ significantly. Evaluation of changes in IL-6, G-CSF, and IFN-γ at 3 weeks after RT initiation can identify patients pre-disposed to severe RP. The mechanism of variation in cytokine levels in relation to RP severity warrants further investigation. [ABSTRACT FROM AUTHOR]

Radioiodine (RI) therapy is known to cause salivary gland (SG) dysfunction. The effects of antioxidants on RI-induced SG damage have not been well described. This study was performed to investigate the radioprotective effects of alpha lipoic acid (ALA) administered prior to RI therapy in a mouse model of RI-induced sialadenitis. Four-week-old female C57BL/6 mice were divided into four groups (n = 10 per group): group I, normal control; group II, ALA alone (100 mg/kg); group III, RI alone (0.01 mCi/g body weight, orally); and group IV, ALA + RI (ALA at 100 mg/kg, 24 h and 30 min before RI exposure at 0.01 mCi/g body weight). The animals in these groups were divided into two subgroups and euthanized at 30 or 90 days post-RI treatment. Changes in salivary 99mTc pertechnetate uptake and excretion were tracked by single-photon emission computed tomography. Salivary histological examinations and TUNEL assays were performed. The 99mTc pertechnetate excretion level recovered in the ALA treatment group. Salivary epithelial (aquaporin 5) cells of the ALA + RI group were protected from RI damage. The ALA + RI group exhibited more mucin-containing parenchyma and less fibrotic tissues than the RI only group. Fewer apoptotic cells were observed in the ALA + RI group compared to the RI only group. Pretreatment with ALA before RI therapy is potentially beneficial in protecting against RI-induced salivary dysfunction. [ABSTRACT FROM AUTHOR]

Background: Meningitis is an inflammatory process involving meninges. It is difficult to diagnose because of the absence of a diagnostic biomarker. We first report here the possibility of cerebrospinal fluid (CSF) vitamin D-binding protein (VDBP) as a new biomarker for the diagnosis of meningitis.Methods: This prospective study enrolled a total of 102 subjects (58 patients with non-neurologic disease, 17 patients with meningitis, and 27 patients with other neurologic diseases) from 2017 to 2018. CSF and blood samples were collected in pairs. Total 25(OH)D in CSF and serum and VDBP levels in serum were measured. GC genotyping was also performed to determine polymorphisms of rs4588 and rs7041. CSF total 25(OH)D and VDBP levels were compared with serum total 25(OH)D and VDBP levels according to disease (meningitis vs. non-meningitis). Receiver operating characteristic (ROC) analysis for the diagnosis of meningitis using CSF VDBP level was performed.Results: Mean CSF VDBP and serum VDBP levels of all patients were 1.48 ± 1.32 and 181.28 ± 56.90 μg/mL, respectively. CSF VDBP level in the meningitis disease group (3.20 ± 1.49 μg/mL) was significantly (P < 0.001) higher than that in other disease groups. According to ROC curve analysis, the appropriate cut-off value for CSF VDBP was 1.96 μg/mL, showing sensitivity of 82.4% and specificity of 85.9%. AUC of CSF VDBP was 0.879 (95% CI: 0.789-0.962).Conclusions: CSF VDBP level showed very good diagnostic performance. It could be used as a potential biomarker for the diagnosis of meningitis. [ABSTRACT FROM AUTHOR]

There is evidence that pepsin can aggravate tonsil hypertrophy. Pepstatin is a potent inhibitor of pepsin activity and could protect patients against reflux tonsil hypertrophy by inhibiting pepsin. We examined the effects of pepstatin on the development of tonsil hypertrophy to investigate pepsin’s role in the pathogenesis of tonsil lesions. We investigated whether pepstatin suppresses pepsin-mediated lymphocyte proliferation in tonsil hypertrophy. Forty-nine children with tonsil hypertrophy and twenty-two adults with tonsillitis were recruited to the study prior to surgery. Tonsil tissue from each patient was harvested and assessed for changes in the number of lymphocytes and macrophages in the presence of pepsin and pepstatin. We found that the proportions of CD4- and CD14-positive cells were significantly lower (p < 0.05), but that the proportions of CD19- and CD68-positive cells were significantly higher (p < 0.05), in children than in adults. There were significantly more CD4-positive cells after pepsin treatment, but these numbers were reduced by pepstatin. The levels of both interleukin-2 (IL-2) and interferon gamma (IFN-γ) increased significantly in response to pepsin, but were reduced when pepsin was inhibited by pepstatin. The level of IL-10 is reduced in pepsin-treated CD4 cells and the level is restored by pepstatin. IL-2 blocking reduced the increased CD4 cell number by pepsin. But, an additive or a synergic effect is not founded in combined with IL-2 blocking and pepstatin. Pepsin-positive cells did not co-localize with CD20 and CD45 cells, but they were found surrounding CD20- and CD45-positive hypertrophic tonsil cells. Pepsin-positive cells co-localized with CD68-positive cells. It is probable that pepsin from extraesophageal reflux aggravates tonsil hypertrophy and pepstatin exerts a protective effect by inhibiting pepsin activity. [ABSTRACT FROM AUTHOR]

Background Although topical corticosteroids are considered a safe and effective drug for allergic rhinitis (AR), some AR patients do not show sufficient symptomatic improvement by use of topical corticosteroids. Topical cyclosporine is a safe and effective drug for patients with allergic conjunctivitis, particularly for those with steroid-resistant allergic conjunctivitis. We investigated the anti-inflammatory effects of intranasal cyclosporine for AR using a mouse model. Methods After establishment of allergic inflammation in 5-week-old BALB/c mice, cyclosporine was administered intranasally 3 times per week for 2 weeks. To confirm its anti-inflammatory effects, triamcinolone acetonide (TAC) was utilized as a control drug. Histopathologic changes were evaluated using Sirius red and Giemsa staining for eosinophilic and mast cell infiltration, respectively. The levels of cytokines in sinonasal tissues, including tumor necrosis factor (TNF), interleukin (IL)-4, IL-5, and IL-13, were assessed based on a cytometric bead array. Results The degree of eosinophilic infiltration was significantly decreased by instillation of cyclosporine, the potency being similar to TAC. However, the number of mast cells was not decreased by cyclosporine or TAC. The levels of TNF, IL-4, IL-5, and IL-13 were significantly decreased after treatment with cyclosporine. Conclusion The anti-inflammatory effects of topical cyclosporine for AR were equivalent to those of topical corticosteroids. Topical cyclosporine may be useful for the treatment of AR, although human studies are required. [ABSTRACT FROM AUTHOR]

Background: Gastroesophageal reflux is associated with numerous pathologic conditions of the upper aerodigestive tract. Gastric pepsin within reflux contributes to immunologic reactions in the tonsil. In this study, we aimed to find the relationships between pepsin and tonsillar hypertrophy. Methods and finding: We explored the notion whether tonsillar hypertrophy was due to pepsin-mediated gastric reflux in tonsil hypertrophy. Fifty-four children with tonsil hypertrophy and 30 adults with tonsillitis were recruited before surgical treatment. Blood and tonsil tissues from each patient were harvested for analysis of changes in lymphocyte and macrophage numbers coupled with histological and biochemical analysis. Pepsin was expressed at different levels in tonsil tissues from each tonsillar hypertrophy. Pepsin-positive cells were found in the crypt epithelium, surrounding the lymphoid follicle with developing fibrosis, and also surrounding the lymphoid follicle that faced the crypt. And also, pepsin staining was well correlated with damaged tonsillar squamous epithelium and TGF-β1 and iNOS expression in the tonsil section. In addition, pepsin and TGF-β1-positive cells were co-localized with CD68-positive cells in the crypt and surrounding germinal centers. In comparison of macrophage responsiveness to pepsin, peripheral blood mononuclear cells (PBMNCs) were noticeably larger in the presence of activated pepsin in the child group. Furthermore, CD11c and CD163-positive cells were significantly increased by activated pepsin. However, this was not seen for the culture of PBMNCs from the adult group. Conclusions: The lymphocytes and monocytes are in a highly proliferative state in the tonsillar hypertrophy and associated with increased expression of pro-inflammatory factors as a result of exposure to stomach reflux pepsin. [ABSTRACT FROM AUTHOR]

Exposure of the thyroid to radiation during radiotherapy of the head and neck is often unavoidable. The present study aimed to investigate the protective effect of α-lipoic acid (ALA) on radiation-induced thyroid injury in rats. Rats were randomly assigned to four groups: healthy controls (CTL), irradiated (RT), received ALA before irradiation (ALA + RT), and received ALA only (ALA, 100 mg/kg, i.p.). ALA was treated at 24 h and 30 minutes prior to irradiation. The neck area including the thyroid gland was evenly irradiated with 2 Gy per minute (total dose of 18 Gy) using a photon 6-MV linear accelerator. Greater numbers of abnormal and unusually small follicles in the irradiated thyroid tissues were observed compared to the controls and the ALA group on days 4 and 7 after irradiation. However, all pathologies were decreased by ALA pretreatment. The quantity of small follicles in the irradiated rats was greater on day 7 than day 4 after irradiation. However, in the ALA-treated irradiated rats, the numbers of small and medium follicles were significantly decreased to a similar degree as in the control and ALA-only groups. The PAS-positive density of the colloid in RT group was decreased significantly compared with all other groups and reversed by ALA pretreatment. The high activity index in the irradiated rats was lowered by ALA treatment. TGF-ß1 immunoreactivity was enhanced in irradiated rats and was more severe on the day 7 after radiation exposure than on day 4. Expression of TGF-ß1 was reduced in the thyroid that had undergone ALA pretreatment. Levels of serum pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) did not differ significantly between the all groups. This study provides that pretreatment with ALA decreased the severity of radiation-induced thyroid injury by reducing inflammation and fibrotic infiltration and lowering the activity index. Thus, ALA could be used to ameliorate radiation-induced thyroid injury. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is the most common condition in hospitalized patients. As ischemia/reperfusion-induced AKI (IR-AKI) is as a major contributor to end-stage disease, an effective therapeutic intervention for IR-AKI is imperative. Erythropoietin (EPO) is a potent stimulator of erythroid progenitor cells and is significantly upregulated during hypoxia. Here, we investigated the renoprotective effects of EPO in an IR-AKI mouse model. Mice were assigned to sham, EPO only, and IR only groups, and the IR group was treated with EPO prior to injury. EPO was administered twice at 30 min prior to bilateral renal artery occlusion, and 5 min before reperfusion, with all mice sacrificed 24 h after IR-AKI. The serum was harvested for renal functional measurements. The kidneys were subjected to histological evaluation, and the biochemical changes associated with renal injury were assessed. EPO significantly attenuated the renal dysfunction associated with IR-AKI, as well as tissue injury. Apoptotic cell death and oxidative stress were significantly reduced in EPO-treated mice. Macrophage infiltration and expression of ICAM-1 and MCP-1 were also significantly reduced in EPO-treated mice. Furthermore, the expression of inflammasome-related factors (NLRP1, NLRP3, and caspase-1 cleavage), via the activation of the COX-2 and NF-κB signaling pathways were significantly reduced following EPO treatment. To our knowledge, this is the first study to demonstrate that inflammasome-mediated inflammation might be a potential target of EPO as a treatment for ischemic AKI. [ABSTRACT FROM AUTHOR]

Radiation therapy is a standard treatment for patients with head and neck cancer. However, radiation exposure to the head and neck induces salivary gland (SG) dysfunction. Alpha lipoic acid (ALA) has been reported to reduce radiation-induced toxicity in normal tissues. In this study, we investigated the effect of ALA on radiation-induced SG dysfunction. Male Sprague–Dawley rats were assigned to the following treatment groups: control, ALA only (100 mg/kg, intraperitoneally), irradiation only, and ALA administration 24 h or 30 min prior to irradiation. The neck area, including SGs, was irradiated evenly at 2 Gy/min (total dose, 18 Gy) using a photon 6 MV linear accelerator. The rats were sacrificed at 2, 6, 8, and 12 weeks after irradiation. Radiation decreased SG weight, saliva secretion, AQP5 expression, parasympathetic innervation (GFRα2 and AchE expression), regeneration potentials (Shh and Ptch expression), salivary trophic factor levels (brain-derived neurotrophic factor and neurturin), and stem cell expression (Sca-1). These features were restored by treatment with ALA. This study demonstrated that ALA can rescue radiation-induced hyposalivation by preserving parasympathetic innervation and regenerative potentials. [ABSTRACT FROM AUTHOR]

The epithelial-to-mesenchymal transition (EMT) is one of mechanisms that induce renal interstitial fibrosis. Understanding EMT in renal fibrosis has important therapeutic implications for patients with kidney disease. Alpha-lipoic acid (ALA) is a natural compound with antioxidant properties. Studies for ALA are performed in acute kidney injury with renal tubular apoptosis, renal inflammation, and oxidative stress. We investigated the effects of ALA on EMT-mediated renal interstitial fibrosis in mice with unilateral ureteral obstruction (UUO). UUO mice developed severe tubular atrophy and tubulointerstitial fibrosis, with a robust EMT response and ECM deposition after 7 postoperative days. In contrast, ALA-treated UUO mice showed only moderate injury and minimal fibrosis and also larger reductions in the expression of ECM proteins, inflammatory factors, and EMT markers. ALA was shown to be involved in the suppression of infiltrating macrophages associated with EMT and the progression of interstitial fibrosis. It also lessened the destruction of the tubular basement membrane, by reducing the expression of matrix metalloproteinases. This is the first study to show that ALA modulates EMT in a UUO mouse model. Our results suggest that ALA merits further exploration as a therapeutic agent in the prevention and treatment of chronic kidney disease. [ABSTRACT FROM AUTHOR]