TGFß4 alleviates the phenotype of Charcot-Marie-Tooth disease type 1A.

The duplication of the peripheral myelin protein 22 (PMP22) gene causes a demyelinating type of neuropathy, commonly known as Charcot-Marie-Tooth disease type 1A (CMT1A). Development of effective drugs for CMT1A still remains as an unmet medical need. In the present study, we assessed the role of the transforming growth factor beta 4 (TGFß4)/Nodal axis in the pathogenesis of CMT1A. First, we identified PMP22 overexpression-induced Nodal expression in Schwann cells, which might be one of the downstream effectors in CMT1A. Administration of Nodal protein at the developmental stage of peripheral nerves induced the demyelinating phenotype in vivo. Second, we further isolated TGFß4 as an antagonist that could abolish Nodal-induced demyelination. Finally, we developed a recombinant TGFß4-fragment crystallizable (Fc) fusion protein, CX201, and demonstrated that its application had promyelinating efficacy in Schwann cells. CX201 administration improved the demyelinating phenotypes of CMT1A mouse models at both pre-symptomatic and post-symptomatic stages. These results suggest that the TGFß4/Nodal axis plays a crucial role in the pathogenesis of CMT1A and might be a potential therapeutic target for CMT1A.

Superoxide Dismutase 3-Transduced Mesenchymal Stem Cells Preserve Epithelial Tight Junction Barrier in Murine Colitis and Attenuate Inflammatory Damage in Epithelial Organoids.

Superoxide dismutase 3 (SOD3), also known as extracellular superoxide dismutase, is an enzyme that scavenges reactive oxygen species (ROS). It has been reported that SOD3 exerts anti-inflammatory abilities in several immune disorders. However, the effect of SOD3 and the underlying mechanism in inflammatory bowel disease (IBD) have not been uncovered. Therefore, in the present study, we investigated whether SOD3 can protect intestinal cells or organoids from inflammation-mediated epithelial damage. Cells or mice were treated with SOD3 protein or SOD3-transduced mesenchymal stem cells (MSCs). Caco-2 cells or intestinal organoids stimulated with pro-inflammatory cytokines were used to evaluate the protective effect of SOD3 on epithelial junctional integrity. Dextran sulfate sodium (DSS)-induced colitis mice received SOD3 or SOD3-transduced MSCs (SOD3-MSCs), and were assessed for severity of disease and junctional protein expression. The activation of the mitogen-activated protein kinase (MAPK) pathway and elevated expression of cytokine-encoding genes decreased in TNF-α-treated Caco-2 cells or DSS-induced colitis mice when treated with SOD3 or SOD3-MSCs. Moreover, the SOD3 supply preserved the expression of tight junction (ZO-1, occludin) or adherence junction (E-cadherin) proteins when inflammation was induced. SOD3 also exerted a protective effect against cytokine- or ROS-mediated damage to intestinal organoids. These results indicate that SOD3 can effectively alleviate enteritis symptoms by maintaining the integrity of epithelial junctions and regulating inflammatory- and oxidative stress.

Porphyromonas gingivalis exacerbates the progression of fatty liver disease via CD36-PPARγ pathway.

Periodontal diseases have been reported to have a multidirectional association with metabolic disorders. We sought to investigate the correlation between periodontitis and diabetes or fatty liver disease using HFD-fed obese mice inoculated with P. gingivalis. Body weight, alveolar bone loss, serological biochemistry, and glucose level were determined to evaluate the pathophysiology of periodontitis and diabetes. For the evaluation of fatty liver disease, hepatic nonalcoholic steatohepatitis (NASH) was assessed by scoring steatosis, inflammation, hepatocyte ballooning and the crucial signaling pathways involved in liver metabolism were analyzed. The C-reactive protein (CRP) level and NASH score in P. gingivalis-infected obese mice were significantly elevated. Particularly, the extensive lobular inflammation was observed in the liver of obese mice infected with P. gingivalis. Moreover, the expression of metabolic regulatory factors, including peroxisome proliferator-activated receptor γ (Pparγ) and the fatty acid transporter Cd36, was up-regulated in the liver of P. gingivalis-infected obese mice. However, inoculation of P. gingivalis had no significant influence on glucose homeostasis, insulin resistance, and hepatic mTOR/AMPK signaling. In conclusion, our results indicate that P. gingivalis can induce the progression of fatty liver disease in HFD-fed mice through the upregulation of CD36-PPARγ axis. [BMB Reports 2021; 54(6): 323-328].

Enhancement of catabolite regulatory genes in Saccharomyces cerevisiae to increase ethanol production using hydrolysate from red seaweed Gloiopeltis furcata.

Glucose and galactose are monosaccharides obtained from Gloiopeltis furcata (Red algae). A total monosaccharide yield of 62.3 g/L was obtained from G. furcata using thermal acid hydrolysis and enzymatic saccharification. Activated carbon was used to eliminate hydroxymethylfurfural (HMF) from the hydrolysate. Previously obtained monosaccharides are used for ethanol production by Saccharomyces cerevisiae. S. cerevisiae consumes glucose first, then galactose. The methods for reducing fermentation time and increasing the ethanol yield coefficient using the simultaneous consumption of glucose and galactose have been evaluated. Gal3p and Gal80p of S. cerevisiae act as signal transducers that govern the galactose inducer Gal4p mediated transcriptional activation of the Gal gene family. Gal80p binds to Gal4p for transcription deactivation. Therefore, Gal80p was deleted for Gal4p expression without interruption.

The impact of writing on academic performance for medical students.

BACKGROUND: Writing is a useful learning activity that promotes higher-order thinking, but there are limited studies that prove its effectiveness. In previous research, researchers tested the effect of summary writing on students' comprehension and found no significant difference from that of re-studying texts. The purpose of this study, therefore, is to expand previous findings and investigate the effect of two types of writing tasks on medical students' academic performance, specifically in the transfer of knowledge. METHODS: An experiment was conducted with 139 medical students from Seoul National University College of Medicine. They were randomly assigned to three study conditions: self-study (SS), expository writing (EW), and argumentative writing (AW) group. Each group studied the given material by the method they were assigned, and they were tested on their comprehension and transfer of knowledge using rote-memory type items and transfer type items respectively. RESULTS: The results showed that the two writing groups displayed better performance than the SS group in transfer type items, while there was no difference in scores between the EW and AW group. However, the three groups showed no significant difference in their scores for rote-memory type items. Also, there was a positive correlation between the writing scores and transfer type item scores in the AW group. CONCLUSIONS: This study provides empirical evidence for writing to be adopted in medical education for greater educational benefits. Our findings indicate that writing can enhance learning and higher-order thinking, which are critical for medical students.

Bioethanol Production from Azolla filiculoides by Saccharomyces cerevisiae, Pichia stipitis, Candida lusitaniae, and Kluyveromyces marxianus.

Ethanol was produced by separate hydrolysis and fermentation using Azolla filiculoides as a biomass. Thermal acid hydrolysis and enzymatic saccharification were used as pretreatment methods to produce monosaccharides from Azolla. The optimal content for thermal acid hydrolysis of 14% (w/v) Azolla weed slurry produced 16.7-g/L monosaccharides by using 200 mM H2SO4 at 121 °C for 60 min. Enzymatic saccharification using 16 U/mL Viscozyme produced 61.6 g/L monosaccharide at 48 h. Ethanol productions with ethanol yield coefficients from Azolla weed hydrolysate using Kluyveromyces marxianus, Candida lusitaniae Saccharomyces cerevisiae, and Pichia stipitis were 26.8 g/L (YEtOH = 0.43), 23.2 g/L (YEtOH = 0.37), 18.2 g/L (YEtOH = 0.29), and 13.7 g/L (YEtOH = 0.22), respectively. Saccharomyces cerevisiae produces the lowest yield as it utilized only glucose. Bioethanol from Azolla weed hydrolysate can be successfully produced by using Kluyveromyces marxianus because it consumed the mixture of glucose and xylose completely within 60 h.

TNF-α Priming Elicits Robust Immunomodulatory Potential of Human Tonsil-Derived Mesenchymal Stem Cells to Alleviate Murine Colitis.

Mesenchymal stem cells (MSCs) have been spotlighted in the field of cell therapies as a promising tool for the treatment of intractable inflammatory diseases. However, their therapeutic potency still shows a gap between preclinical and clinical settings, and distinctive characteristics of specific tissue-derived MSCs and definitive ways to maximize their beneficial functions have not been fully elucidated yet. We previously identified the unique MSCs population from human palatine tonsil (TMSCs) and revealed their superior properties in proliferation and ROS regulation. Based on these findings, we explored further characteristics of TMSCs particularly focused on immunomodulatory function. We found the merit of TMSCs as a therapeutic agent that retains favorable MSCs properties until relatively late passages and revealed that pre-treatment of TNF-α can enhance the immunomodulatory abilities of TMSCs through the upregulation of the PTGS2/PGE2 axis. TMSCs primed with TNF-α effectively restrained the proliferation and differentiation of T lymphocytes and macrophages in vitro, and more interestingly, these TNF-α-licensed TMSCs exhibited significant prophylactic and therapeutic efficacy in a murine model of autoimmune-mediated acute colitis via clinical and histopathological assessment compared to unprimed naïve TMSCs. These findings provide novel insight into the optimization and standardization of MSCs-based anti-inflammatory therapies, especially targeting inflammatory bowel disease (IBD).

Extracellular Vesicles from SOD3-Transduced Stem Cells Exhibit Improved Immunomodulatory Abilities in the Murine Dermatitis Model.

The immunoregulatory abilities of mesenchymal stem cells (MSCs) have been investigated in various autoimmune and allergic diseases. However, the therapeutic benefits observed in preclinical settings have not been reproducible in clinical trials. This discrepancy is due to insufficient efficacy of MSCs in harsh microenvironments, as well as batch-dependent variability in potency. Therefore, to achieve more beneficial and uniform outcomes, novel strategies are required to potentiate the therapeutic effect of MSCs. One of simple strategies to augment cellular function is genetic manipulation. Several studies showed that transduction of antioxidant enzyme into cells can increase anti-inflammatory effects. Therefore, we evaluated the immunoregulatory abilities of MSCs introduced with extracellular superoxide dismutase 3 (SOD3) in the present study. SOD3-overexpressed MSCs (SOD3-MSCs) reduced the symptoms of murine model of atopic dermatitis (AD)-like inflammation, as well as the differentiation and activation of various immune cells involved in AD progression. Interestingly, extracellular vesicles (EVs) isolated from SOD3-MSCs delivered SOD3 protein. EVs carrying SOD3 also exerted improved therapeutic efficacy, as observed in their parent cells. These results suggest that MSCs transduced with SOD3, an antioxidant enzyme, as well as EVs isolated from modified cells, might be developed as a promising cell-based therapeutics for inflammatory disorders.

Topical cell-free conditioned media harvested from adipose tissue-derived stem cells promote recovery from corneal epithelial defects caused by chemical burns.

Corneal chemical burns can lead to blindness following serious complications. As most of these complications are caused by failure of reepithelization during the acute phase, treatment at this stage is critical. Although there have been some studies on corneal injury recovery using adipose tissue-derived stem cells (ADSCs), none has reported the effect of topical cell-free conditioned culture media (CM) derived from ADSCs on corneal epithelial regeneration. Here, the best conditions for CM were selected and used for in vitro and in vivo experiments. Corneal burn in rats was induced using 100% alcohol. The chosen CM was administered to corneal burn rats (CM-treated [CT] group) four times a day for three days and this group was compared with the normal control and corneal burn (CB) groups. Biomicroscopic fluorescence images and the actual physical corneas were taken over time and used for analysis. mRNA levels of hepatocyte growth factor and epidermal growth factor (EGF) were significantly increased, whereas those of vascular endothelial growth factor, interleukin (IL)-1ß, IL-6, IL-10, and matrix metalloproteinase-9 were significantly decreased in the CT group compared with those in the CB group. The numbers of proliferating cell nuclear antigen- and zonular occludens-1-positive cells in the CT group were significantly higher than those in the CB group. The macrophage-infiltrating corneas in the CT group expressed significantly more of the M2 marker arginase than corneas in the CB group. Optimal CM (× 0.5 concentration) treatment significantly accelerated the migration of corneal epithelial cells and induced upregulation of the expression of IL-6, EGF, and C-X-C chemokine receptor type 4 mRNAs. Overall, in this study, topical administration of cell-free CM promoted regeneration of the corneal epithelium after induction of chemical burns.

Therapeutic Functions of Stem Cells from Oral Cavity: An Update.

Adult stem cells have been developed as therapeutics for tissue regeneration and immune regulation due to their self-renewing, differentiating, and paracrine functions. Recently, a variety of adult stem cells from the oral cavity have been discovered, and these dental stem cells mostly exhibit the characteristics of mesenchymal stem cells (MSCs). Dental MSCs can be applied for the replacement of dental and oral tissues against various tissue-damaging conditions including dental caries, periodontitis, and oral cancers, as well as for systemic regulation of excessive inflammation in immune disorders, such as autoimmune diseases and hypersensitivity. Therefore, in this review, we summarized and updated the types of dental stem cells and their functions to exert therapeutic efficacy against diseases.

The activation of NLRP3 inflammasome potentiates the immunomodulatory abilities of mesenchymal stem cells in a murine colitis model.

Inflammasomes are cytosolic, multiprotein complexes that act at the frontline of the immune responses by recognizing pathogen- or danger-associated molecular patterns or abnormal host molecules. Mesenchymal stem cells (MSCs) have been reported to possess multipotency to differentiate into various cell types and immunoregulatory effects. In this study, we investigated the expression and functional regulation of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome in human umbilical cord blood-derived MSCs (hUCB-MSCs). hUCB-MSCs expressed inflammasome components that are necessary for its complex assembly. Interestingly, NLRP3 inflammasome activation suppressed the differentiation of hUCB-MSCs into osteoblasts, which was restored when the expression of adaptor proteins for inflammasome assembly was inhibited. Moreover, the suppressive effects of MSCs on T cell responses and the macrophage activation were augmented in response to NLRP3 activation. In vivo studies using colitic mice revealed that the protective abilities of hUCB-MSCs increased after NLRP3 stimulation. In conclusion, our findings suggest that the NLRP3 inflammasome components are expressed in hUCB-MSCs and its activation can regulate the differentiation capability and the immunomodulatory effects of hUCB-MSCs. [BMB Reports 2020; 53(6): 329-334].

Human Tonsil-Derived Mesenchymal Stromal Cells Maintain Proliferating and ROS-Regulatory Properties via Stanniocalcin-1.

Mesenchymal stromal cells (MSCs) from various sources exhibit different potential for stemness and therapeutic abilities. Recently, we reported a unique MSCs from human palatine tonsil (TMSCs) and their superior proliferation capacity compared to MSCs from other sources. However, unique characteristics of each MSC are not yet precisely elucidated. We investigated the role of stanniocalcin-1 (STC1), an anti-oxidative hormone, in the functions of TMSCs. We found that STC1 was highly expressed in TMSC compared with MSCs from bone marrow or adipose tissue. The proliferation, senescence and differentiation of TMSCs were assessed after the inhibition of STC1 expression. STC1 inhibition resulted in a significant decrease in the proliferation of TMSCs and did not affect the differentiation potential. To reveal the anti-oxidative ability of STC1 in TMSCs themselves or against other cell types, the generation of mitochondrial reactive oxygen species (ROS) in TMSC or ROS-mediated production of interleukin (IL)-1ß from macrophage-like cells were detected. Interestingly, the basal level of ROS generation in TMSCs was significantly elevated after STC1 inhibition. Moreover, down-regulation of STC1 impaired the inhibitory effect of TMSCs on IL-1ß production in macrophages. Taken together, these findings indicate that STC1 is highly expressed in TMSCs and plays a critical role in proliferating and ROS-regulatory abilities.

Echinochrome A Reduces Colitis in Mice and Induces In Vitro Generation of Regulatory Immune Cells.

Echinochrome A (Ech A), a natural pigment extracted from sea urchins, is the active ingredient of a marine-derived pharmaceutical called 'histochrome'. Since it exhibits several biological activities including anti-oxidative and anti-inflammatory effects, it has been applied to the management of cardiac injury and ocular degenerative disorders in Russia and its protective role has been studied for other pathologic conditions. In the present study, we sought to investigate the therapeutic potential of Ech A for inflammatory bowel disease (IBD) using a murine model of experimental colitis. We found that intravenous injection of Ech A significantly prevented body weight loss and subsequent lethality in colitis-induced mice. Interestingly, T cell proliferation was significantly inhibited upon Ech A treatment in vitro. During the helper T (Th) cell differentiation process, Ech A stimulated the generation regulatory T (Treg) cells that modulate the inflammatory response and immune homeostasis. Moreover, Ech A treatment suppressed the in vitro activation of pro-inflammatory M1 type macrophages, while inducing the production of M2 type macrophages that promote the resolution of inflammation and initiate tissue repair. Based on these results, we suggest that Ech A could provide a beneficial impact on IBD by correcting the imbalance in the intestinal immune system.

Carbon balance of major volatile fatty acids (VFAs) in recycling algal residue via a VFA-platform for reproduction of algal biomass.

The feasibility of a carbon recycling system that transforms algal residue to volatile fatty acids (VFAs) for re-cultivating microalgae was evaluated based on a carbon balance analysis of major VFAs consisting of acetate (HAc), propionate (HPr), and butyrate (HBu). This system largely involves two processes: (i) bioconversion of algal residue to VFAs by anaerobic fermentation, and (ii) cultivation of microalgae using the produced VFAs. The carbon balance for each unit process was examined to assess how much carbon in algal residue can be converted to these major VFAs and then assimilated to microalgae biomass. First, the yield and the profile of VFAs from raw algae (RA) and lipid-extracted algae (LEA) at psychrophilic (15 °C), mesophilic (35 °C), and thermophilic conditions (55 °C) were compared. When digesting the LEA under the thermophilic condition, the highest conversion yield, 0.36 (g carbon in VFAs/g carbon in biomass), with a compositional ratio of 6:1:3 (HAc: HPr: HBu) was obtained. Consumption of VFAs for microalgal growth reached a maximum value of 0.66 (g VFAs assimilated to biomass/g VFAs provided) at the compositional ratio of 6:1:3. Consequently, the maximum total carbon recycling ratio was 23.8% when fermenting LEA at the thermophilic condition. Our findings comprehensively revealed that establishing conditions that convert LEA to higher content of acetate is a decisive factor. It was estimated that around 40% of the total carbon from the LEA can be recovered for the production of algal biomass, when increasing the VFA conversion yield beyond 60% by adopting pretreatment methods.

Implication of Porphyromonas gingivalis in colitis and homeostasis of intestinal epithelium.

Emerging evidences have reported that periodontitis can be a risk factor for the pathogenesis of various systemic diseases. Porphyromonas gingivalis (Pg), one of the crucial pathogens in chronic periodontitis, has been spotlighted as a potential cause for the promotion and acceleration of periodontitis-associated systemic disorders. To investigate the association between Pg and intestinal disease or homeostasis, we treated Pg-derived lipopolysaccharide (LPS) in murine colitis model or intestinal organoid, respectively. Pg-derived LPS (Pg LPS) was administrated into chemically induced murine colitis model and disease symptoms were monitored compared with the infusion of LPS derived from E. coli (Ec LPS). Organoids isolated and cultured from mouse small intestine were treated with Pg or Ec LPS and further analyzed for the generation and composition of organoids. In vivo observations demonstrated that both Pg and Ec LPS exerted slight protective effects against murine colitis. Pg LPS did not affect the generation and growth of intestinal epithelial organoids. Among subtypes of epithelial cells, markers for stem cells, goblet cells or Paneth cells were changed in response to Pg LPS. Taken together, these results indicate that Pg LPS leads to partial improvement in colitis and that its treatment does not significantly affect the self-organization of intestinal organoids but may regulate the epithelial composition.

Active learning through discussion: ICAP framework for education in health professions.

BACKGROUND: The ICAP framework based on cognitive science posits four modes of cognitive engagement: Interactive, Constructive, Active, and Passive. Focusing on the wide applicability of discussion as interactive engagement in medical education, we investigated the effect of discussion when it was preceded by self-study and further investigated the effect of generating questions before discussions. METHODS: This study was conducted in the second semester of 2018 and was participated in by 129 students majoring in health professions, including medicine, dentistry, veterinary medicine, and nursing. The students were assigned to four different trial groups and were asked to fill out a Subjective Mental Effort Questionnaire after completing each session. Their performance in posttest scores was analyzed using Bonferroni test, and mental effort was analyzed using mediation analysis. RESULTS: These results indicated that the self-study and question group had the highest performance and that the lecture and summary group had the lowest performance when comparing the total score. Using the analysis of mental effort, it was confirmed that the relationship between different study conditions and post-test performance was mediated by mental effort during test. CONCLUSIONS: Our findings support the ICAP framework and provide practical implications for medical education, representing the fact that students learn more when they are involved in active learning activities, such as self-study and question generation, prior to discussions.

Application of the international league against rheumatism classification criteria for systemic juvenile idiopathic arthritis as a prognostic factor in patients with adults-onset Still's disease.

BACKGROUND: Adult-onset Still's disease (AOSD) is an adult form of systemic juvenile idiopathic arthritis (JIA) that differs from the latter in its classification. This study evaluated the concordance between the International League Against Rheumatism (ILAR) criteria for systemic JIA and the Yamaguchi criteria and then compared their possible prognostic value in patients with AOSD. METHODS: In a retrospective review of 169 adults with suspected AOSD, patients were classified according to the Yamaguchi or ILAR criteria. Then the concordance in cross-referencing the other group with the different criteria was investigated and the sensitivity and specificity of each set of criteria were determined. Disease activity markers in AOSD patients were correlated with positivity according to both systems. RESULTS: Concordance was good in patients with suspected AOSD (k = 0.7144, p <  0.001) and low in those with a diagnosis of AOSD (k = 0.3787, p <  0.001). The sensitivity of the ILAR criteria in AOSD patients was 0.8864 (95% confidence interval (CI): 0.8322-0.9405), and the specificity was 0.7838 (0.6511, 0.9164). Positivity according to the ILAR criteria correlated with the systemic score (r = 0.763, p <  0.0001) and C-reactive protein levels (r = 0.183, p = 0.0356) and was associated with a relapse (odds ratio: 1.589, 95% CI: 1.043-2.421), macrophage activation syndrome (MAS; odds ratio: 1.993, 95% CI: 1.218-3.263) and care in the intensive care unit (ICU; odds ratio: 2.087, 95% CI: 1.086-4.011). CONCLUSIONS: In AOSD patients, there is fair concordance between the Yamaguchi and ILAR criteria for systemic JIA. Positive ILAR criteria may be useful for identifying AOSD patients at high risk for relapse, MAS and the need for ICU care. Further studies including larger populations from several centers are needed to confirm our results regarding the utility of the ILAR criteria in AOSD patients.

The neutrophil-to-lymphocyte ratio could be a good diagnostic marker and predictor of relapse in patients with adult-onset Still's disease: A STROBE-compliant retrospective observational analysis.

The neutrophil-to-lymphocyte ratio (NLR) is the proportion of absolute neutrophil count to lymphocytes on routine complete blood count (CBC) tests, and has been studied as a simple marker of the systemic inflammatory response. This study was performed to investigate whether the NLR could be used as a tool to diagnose and predict prognosis in cases of adult-onset Still's disease (AOSD).We retrospectively reviewed 164 patients with suspected AOSD. Among 164 patients with suspected AOSD, 37 patients received another diagnosis (such as viral infection) and were compared with the 127 patients who received a diagnosis of AOSD. Laboratory tests including CBCs, ferritin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and the NLR were evaluated.AOSD patients showed higher neutrophil counts, lower lymphocyte counts, higher NLRs, and higher levels of ferritin, ESR, and CRP than non-AOSD patients (all P < .001). In receiver operating characteristic (ROC) curve analysis of the NLR for diagnosis of AOSD, the area under the curve (AUC) was highest at 0.967 (95% CI = 0.940-0.993) with a cutoff value of 3.08. The cutoff value showed the greatest sensitivity (91.7%), specificity (68.4%), and AUC value (0.967) as a diagnostic tool for AOSD. The NLR and treatment appeared to be significant prognostic factors for relapse, but only age showed a significant relationship with death. Furthermore, the NLR was significantly higher in patients with macrophage activation syndrome than in hemophagocytic lymphohistiocytosis (HLH) patients (P = .007). In ROC analysis, the NLR with a cutoff value of 5.86 showed a sensitivity of 89.4%, specificity of 87.8%, and AUC of 0.794.The NLR can be used as a diagnostic tool and predictor of relapse in AOSD, and for differential diagnosis of HLH.

The role of phenylephrine in patients with small deep subcortical infarct and progressive weakness.

BACKGROUND AND PURPOSE: Although progression of small deep subcortical infarct (PSDI) comprises 12% to 36% of all small deep subcortical infarcts, the therapy for progression is not clear. This study investigated whether induced-hypertension therapy using phenylephrine is a useful therapy for PSDI. METHODS: A group of 2427 consecutive patients, diagnosed with stroke at a tertiary hospital over a period of 4years was reviewed retrospectively. We analyzed patients with small deep subcortical infarct using clinical, laboratory, and pulse wave velocity (PWV). PSDI is defined as one or more increase in the motor score according to the NIHSS. Good outcome was designated as a modified Rankin scale of 0 to 2 at discharge. RESULTS: Among all 662 patients who had a small deep subcortical infarct, 66 patients experienced motor progression (9.97%). The induced-hypertension therapy group (n=25) received phenylephrine, and the conventional group (n=41) received anticoagulation therapy such as heparin, volume expansion, or both. Although there were no significant differences in baseline clinical and laboratory findings, the PSDI group showed a significantly more frequent decrease in blood pressure at progression (P<0.0001) and higher PWV (P=0.001). The phenylephrine group (vs the conventional group) had a lower NIHSS score (P=0.036) and good outcome at discharge (P=0.004). In multiple regression analysis, PWV (OR, 1.004 per 1-cm/s increase; 95% CI, 1.001-1.008; P=0.018) was an independent predictor of good outcome in the phenylephrine group. A side effect of phenylephrine treatment was dysuria (n=1). CONCLUSIONS: The present study suggests that vascular stiffness can be not only a predictor for PSDI but also a predictor of motor improvement after induced-hypertension therapy using phenylephrine in lacunar stroke.