CDDO regulates central and peripheral sensitization to attenuate post-herpetic neuralgia by targeting TRPV1/PKC-δ/p-Akt signals.

Postherpetic neuralgia (PHN) is a notorious neuropathic pain featuring persistent profound mechanical hyperalgesia with significant negative impact on patients' life quality. CDDO can regulate inflammatory response and programmed cell death. Its derivative also protects neurons from damages by modulating microglia activities. As a consequence of central and peripheral sensitization, applying neural blocks may benefit to minimize the risk of PHN. This study aimed to explore whether CDDO could generate analgesic action in a PHN-rats' model. The behavioural test was determined by calibrated forceps testing. The number of apoptotic neurons and degree of glial cell reaction were assessed by immunofluorescence assay. Activation of PKC-δ and the phosphorylation of Akt were measured by western blots. CDDO improved PHN by decreasing TRPV1-positive nociceptive neurons, the apoptotic neurons, and reversed glial cell reaction in adult rats. It also suppressed the enhanced PKC-δ and p-Akt signalling in the sciatic nerve, dorsal root ganglia (DRG) and spinal dorsal horn. Our research is the promising report demonstrating the analgesic and neuroprotective action of CDDO in a PHN-rat's model by regulating central and peripheral sensitization targeting TRPV1, PKC-δ and p-Akt. It also is the first study to elucidate the role of oligodendrocyte in PHN.

RTA-408 Regulates p-NF-κB/TSLP/STAT5 Signaling to Ameliorate Nociceptive Hypersensitivity in Chronic Constriction Injury Rats.

Neuropathic pain following nerve injury is a complex condition, which often puts a negative impact on life and remains a sustained problem. To make pain management better is of great significance and unmet need. RTA 408 (Omaveloxone) is a traditional Asian medicine with a valid anti-inflammatory property. Thus, we aim to investigate the therapeutic effect of RTA-408 on mechanical allodynia in chronic constriction injury (CCI) rats as well as the underlying mechanisms. Neuropathic pain was induced by using CCI of the rats' sciatic nerve (SN) and the behavior testing was measured by calibrated forceps testing. Activation of Nrf-2, the phosphorylation of nuclear factor-κB (NF-κB), and the inflammatory response were assessed by western blots. The number of apoptotic neurons and degree of glial cell reaction were examined by immunofluorescence assay. RTA-408 exerts an analgesic effect on CCI rats. RTA-408 reduces neuronal apoptosis and glial cell activation by increasing Nrf-2 expression and decreasing the inflammatory response (TNF-α/ p-NF-κB/ TSLP/ STAT5). These data suggest that RTA-408 is a candidate with potential to reduce nociceptive hypersensitivity after CCI by targeting TSLP/STAT5 signaling.

Linalyl Acetate Ameliorates Mechanical Hyperalgesia Through Suppressing Inflammation by TSLP/IL-33 Signaling.

Neuropathic pain is a debilitating chronic disorder, significantly causing personal and social burdens, in which activated neuroinflammation is one major contributor. Thymic stromal lymphopoietin (TSLP) and interleukin (IL)-33 is important for chronic inflammation. Linalyl acetate (LA) is main component of lavender oil with an anti-inflammatory property through TSLP signaling. The aim of the study is to investigate how LA regulates mechanical hyperalgesia after sciatic nerve injury (SNI). Adult Sprague-Dawley male rats were separated into 3 groups: control group, SNI group and SNI with LA group. LA was administrated intraperitoneally one day before SNI. Pain behavior test was evaluated through calibration forceps testing. Ipsilateral sciatic nerves (SNs), dorsal root ganglions (DRGs) and spinal cord were collected for immunofluorescence staining and Western blotting analyses. SNI rats were more sensitive to hyperalgesia response to mechanical stimulus since operation, which was accompanied by spinal cord glial cells reactions and DRG neuro-glial interaction. LA could relieve the pain sensation, proinflammatory cytokines and decrease the expression of TSLP/TSLPR complex. Also, LA could reduce inflammation through reducing IL-33 signaling. This study is the first to indicate that LA can modulate pain through TSLP/TSLPR and IL-33 signaling after nerve injury.

Observation of Curative Effect of Trimetazidine Combined with Metoprolol in Elderly Patients with Coronary Heart Disease Complicated with Heart Failure and the Effect of Myocardial Remodeling by Integrated Traditional Chinese and Western Medicine.

Diabetic retinopathy (DR) is the most common complication of diabetes and is often characterized by damage to retinal vascular microcirculation, resulting in retinal exudation, hemorrhage, fibrosis, and neovascularization. With the aging of my country's population, the incidence of DR is increasing year by year, and it has become one of the main blinding eye diseases in ophthalmic diseases also tends to be younger. So far, although the pathogenesis of DR is not completely clear, scholars generally believe that DR is based on the disorder of glucose metabolism, causing changes in the microcirculation of ocular tissues, nerves, and blood vessels, resulting in chronic damage to the nutrition and visual function of the eye disease. In order to explore the demand for cardiovascular disease treatment, make up for the lack of chronic diseases affecting people's physical harm, and improve the success rate of cardiovascular disease treatment, a method to observe the efficacy and myocardial remodeling of trimetazidine combined with metoprolol in elderly patients with coronary heart disease and heart failure based on integrated traditional Chinese and Western medicine was proposed. 54 elderly people over 60 years old are afraid of cardiovascular disease and take active protection. A method based on observation of integrated traditional Chinese and Western medicine was proposed, and at the same time, an intelligent medical monitoring system was constructed to better study, observe, and improve the efficacy of trimetazidine combined with metoprolol in elderly patients with coronary heart disease, heart failure, and myocardial impact of refactoring. The results of the study show that trimetazidine has a good clinical effect on ischemic cardiomyopathy heart failure based on the observation of integrated traditional Chinese and Western medicine.

Prognostic Impact of Low-Level p53 Expression on Brain Astrocytomas Immunopositive for Epidermal Growth Factor Receptor.

Although the expression of p53 and epidermal growth factor receptor (EGFR) is associated with therapeutic resistance and patient outcomes in many malignancies, the relationship in astrocytomas is unclear. This study aims to correlate p53 and EGFR expression in brain astrocytomas with overall patient survival. Eighty-two patients with astrocytomas were enrolled in the study. Semi-quantitative p53 and EGFR immunohistochemical staining was measured in tumor specimens. The mean follow-up after astrocytoma surgery was 18.46 months. The overall survival rate was 83%. Survival was reduced in EGFR-positive patients compared with survival in EGFR-negative patients (p < 0.05). However, no significant differences in survival were detected between patients with high and low p53 expression. In patients with low p53 expression, positive EGFR staining was associated with significantly worse survival compared with patients with negative EGFR staining (log-rank test: p < 0.001). Survival rates in positive and negative EGFR groups with high p53 protein expression were similar (log-rank test: p = 0.919). The IC50 of an EGFR inhibitor was higher in GBM cells with high p53 protein expression compared with the IC50 in cells with low p53 expression. Combined EGFR and p53 expression may have prognostic significance in astrocytomas.

Impact of seborrheic dermatitis on osteoporosis risk: A population-based cohort study.

Osteoporosis is a systemic bone-resorbing disease that easily causes subsequent risk of fracture. Hence, the substantial physical burden of osteoporosis makes it an important public health issue. Seborrheic dermatitis (SD) is a chronic, recurrent, inflammatory skin disease. Despite the advances in medication for treating osteoporosis, identifying undiagnosed osteoporosis patients is still challenging. Since osteoporosis and SD share a similar pathobiology, e.g. inflammation and hormonal imbalance, we aimed to investigate whether the existence of SD increases osteoporosis risk by using the Taiwan National Health Insurance Research Database. A total of 7831 patients aged 18-50 years with SD and a control group of 31 324 patients without SD matched by age, gender, Charlson Comorbidity Index, and index date at a ratio of 1:4 during 1996-2010 were recruited in the study. To measure the cumulative incidence and compare the hazard ratios of osteoporosis between each group, the Kaplan-Meier method and Cox proportional hazard regression models were utilized. It was found that 0.98% of SD patients had osteoporosis. Compared to the non-SD group, the SD group had a 5.95-fold higher osteoporosis risk after adjustment for variables. The impact of SD on osteoporosis risk was largest in the female and young age groups. In addition, the presence of hyperlipidemia, hyperthyroidism, and epilepsy synergistically increased osteoporosis incidence in the SD group. This first large cohort study demonstrated an association between SD and osteoporosis. Since the effect on bone health in SD patients with concomitant diseases is largest in early life, diet or lifestyle recommendations as well as regular bone examinations are advised during follow-up of SD.

Trigeminal Neuralgia Is a Dementia Risk Factor: A Retrospective Cohort Study.

Background: Dementia, a worldwide public-health issue, is regarded as a disorder rather than a normal aging process. Trigeminal neuralgia (TN) is a chronic debilitating pain disorder that impairs daily activities. Both are most prevalent in females and in patients older than 50 years. Recent studies reveal that pain and dementia may have a reciprocal interaction with each other. Objective: In response, we estimated whether adults with TN have an increased dementia risk. Methodology: By means of Taiwan's National Health Insurance Research Database, between 1996 and 2010, 762 patients aged over 50 years in the TN group were matched with 3048 patients in the non-TN group at a ratio of 1:4. Kaplan-Meier method and Cox proportional hazard regression models were also used to determine the cumulative incidence and compare the hazard ratios of dementia in each group. Results: The incidence of dementia was higher in the TN group compared to the non-TN group. After adjusting for covariates, the TN group had a 4.47-fold higher risk of dementia compared to the non-TN group. Additionally, the impact of TN on dementia risk was larger in young-aged patients than in old-aged patients. As well, the age at the time of dementia diagnosis was younger in the TN group compared to the non-TN group. Conclusions: TN is a dementia risk factor. Given the lack of a curative therapy for dementia, early identification of TN patients may help to prevent dementia sequelae.

The Contribution of TSLP Activation to Hyperalgesia in Dorsal Root Ganglia Neurons of a Rat.

Peripheral nerve injury involves divergent alterations within dorsal root ganglia (DRG) neurons sensitized by persistent inflammation. Thymic stromal lymphopoietin (TSLP) production is crucial in the development of chronic inflammatory responses. Herein, we investigate the changes of TSLP expression in rats' DRG neurons between injured and uninjured sides in the same rat. Linalyl acetate (LA) was served as a TSLP inhibitor and given intraperitoneally. Rats were assigned to be group of chronic constriction injury (CCI) of the sciatic nerve and the group of CCI of the sciatic nerve administrated with LA. Over 14 days, the rats were measured for paw withdrawal thresholds. DRGs were collected to assess morphological changes via immunofluorescence study. After receiving CCI, the rats rapidly developed mechanical hyperalgesia. TSLP expression at DRG, on the ipsilateral injured side, was consistent with changes in pain behaviors. TSLP appeared in nerve fibers with both small diameters and large diameters. Additionally, TSLP was expressed mostly in transient receptor potential vanilloid-1 (TRPV1)-positive nociceptive neurons. Administration with LA can attenuate the pain behaviors and expression of TSLP in DRG neurons, and in apoptotic neurons at the injured side, but not in the contra-lateral uninjured side. Overall, these results imply that altered expressions of TSLP in nociceptive DRG neurons contributed to mechanical hyperalgesia in a CCI rat model.

2-PMAP Ameliorates Cerebral Vasospasm and Brain Injury after Subarachnoid Hemorrhage by Regulating Neuro-Inflammation in Rats.

A subarachnoid hemorrhage (SAH), leading to severe disability and high fatality in survivors, is a devastating disease. Neuro-inflammation, a critical mechanism of cerebral vasospasm and brain injury from SAH, is tightly related to prognoses. Interestingly, studies indicate that 2-[(pyridine-2-ylmethyl)-amino]-phenol (2-PMAP) crosses the blood-brain barrier easily. Here, we investigated whether the vasodilatory and neuroprotective roles of 2-PMAP were observed in SAH rats. Rats were assigned to three groups: sham, SAH and SAH+2-PMAP. SAHs were induced by a cisterna magna injection. In the SAH+2-PMAP group, 5 mg/kg 2-PMAP was injected into the subarachnoid space before SAH induction. The administration of 2-PMAP markedly ameliorated cerebral vasospasm and decreased endothelial apoptosis 48 h after SAH. Meanwhile, 2-PMAP decreased the severity of neurological impairments and neuronal apoptosis after SAH. Furthermore, 2-PMAP decreased the activation of microglia and astrocytes, expressions of TLR-4 and p-NF-κB, inflammatory markers (TNF-α, IL-1ß and IL-6) and reactive oxygen species. This study is the first to confirm that 2-PMAP has vasodilatory and neuroprotective effects in a rat model of SAH. Taken together, the experimental results indicate that 2-PMAP treatment attenuates neuro-inflammation, oxidative stress and cerebral vasospasm, in addition to ameliorating neurological deficits, and that these attenuating and ameliorating effects are conferred through the TLR-4/NF-κB pathway.

Migraines and keloids: a 15-year Taiwan claim database analysis.

BACKGROUND: Fibroproliferative lesions with intractable pruritus, pain and hyperesthesia that cause uncontrolled scar growth are known as keloids. Migraines are common upsetting headache disorders characterised by frequent recurrence and attacks aggravated by physical activity. Both keloids and migraines can cause physical exhaustion and discomfort in patients; they have similar pathophysiological pathways, that is, the transforming growth factor-ß1 gene and neurogenic inflammation. OBJECTIVE: To investigate subsequent development of migraines in patients with keloids. Methods Data were retrieved from the Taiwan National Health Insurance Research Database. The keloids group included patients aged 20 years and older with a recent diagnosis of keloids(n=9864). The non-keloids group included patients without keloids matched for gender and age at 1-4 ratio (n=39 456). Migraine risk between groups was measured by Cox proportional hazards regression models. Incidence rates and hazard ratios were calculated. RESULTS: During the study period, 103 keloids patients and 323 non-keloids patients developed migraines. The keloids patients had a 2.29-fold greater risk of developing migraines compared with the non-keloids group after adjustment for covariates (1.81 vs 0.55 per 1000 person-years, respectively). In the keloids group, female or patients younger than 50 years were prone to developing migraines. CONCLUSION: The higher tendency to develop migraines in the keloids group in comparison with the non-keloids group suggests that keloids could be a predisposing risk factor for migraine development in adults. Keloids patients who complain of headaches should be examined for migraines.

Increased Expression of Thymic Stromal Lymphopoietin in Chronic Constriction Injury of Rat Nerve.

Thymic stromal lymphopoietin (TSLP) is a well-known cytokine for T helper 2 inflammatory responses. A nerve injury activates the neuroinflammation cascade and neuron-glia interaction in dorsal root ganglions (DRG)s, leading to neuropathic pain. Therefore, this study was to investigate the role of TSLP after nerve injury. Male Sprague-Dawley rats were divided as an experimental group with chronic constriction injury (CCI) to the sciatic nerve and a control group. The mechanical pain threshold response was determined by calibration forceps. After assessment of mechanical allodynia, the ipsilateral spinal cord, DRG, sciatic nerve and skin were harvested. Immunofluorescence staining was performed to identify cell types with various markers. Western blot analyses were performed to evaluate protein expressions. Mechanical allodynia developed after CCI and persisted for the next 14 days. Astrocyte reactions occurred and continued until day 14, too. After CCI, DRG and the sciatic nerve also had significantly increased expressions of TSLP/TSLP-R/STAT5. The TSLPR was localized to sensory neuronal endings innervating the skin. This study is the first to demonstrate that the TSLP complex and the STAT5 pathway in nerve are potential therapeutic targets because of their roles in pain regulation after nerve injury.

GLUT-1 Enhances Glycolysis, Oxidative Stress, and Fibroblast Proliferation in Keloid.

A keloid is a fibroproliferative skin tumor. Proliferating keloid fibroblasts (KFs) demand active metabolic utilization. The contributing roles of glycolysis and glucose metabolism in keloid fibroproliferation remain unclear. This study aims to determine the regulation of glycolysis and glucose metabolism by glucose transporter-1 (GLUT-1), an essential protein to initiate cellular glucose uptake, in keloids and in KFs. Tissues of keloids and healthy skin were explanted for KFs and normal fibroblasts (NFs), respectively. GLUT-1 expression was measured by immunofluorescence, RT-PCR, and immunoblotting. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured with or without WZB117, a GLUT-1 inhibitor. Reactive oxygen species (ROS) were assayed by MitoSOX immunostaining. The result showed that glycolysis (ECAR) was enhanced in KFs, whereas OCR was not. GLUT-1 expression was selectively increased in KFs. Consistently, GLUT-1 expression was increased in keloid tissue. Treatment with WZB117 abolished the enhanced ECAR, including glycolysis and glycolytic capacity, in KFs. ROS levels were increased in KFs compared to those in NFs. GLUT-1 inhibition suppressed not only the ROS levels but also the cell proliferation in KFs. In summary, the GLUT-1-dependent glycolysis and ROS production mediated fibroblast proliferation in keloids. GLUT1 might be a potential target for metabolic reprogramming to treat keloids.

Risk of cancer development in patients with keloids.

Keloid is a skin disease characterized by exaggerated scar formation, excessive fibroblast proliferation, and excessive collagen deposition. Cancers commonly arise from a fibrotic microenvironment; e.g., hepatoma arises from liver cirrhosis, and oral cancers arise from submucosal fibrosis. As keloids are a prototypic fibroproliferative disease, this study investigated whether patients with keloids have an increased cancer risk. In a matched, population-based study, first 17,401 patients treated for keloids during 1998-2010 with 69,604 controls without keloids at a ratio of 1:4 were evaluated. The association between keloids and risk of cancer was estimated by logistic regression or Cox proportional hazard regression models after adjustment of covariates. In total, 893 first-time cases of cancer were identified in the 17,401 patients with keloids. The overall cancer risk was 1.49-fold higher in the keloids group compared to controls. Regarding specific cancers, the keloids group, had a significantly higher risk of skin cancer compared to controls (Relative risk = 1.73). The relative risk for skin cancer was even higher for males with keloids (Relative risk = 2.16). Further stratified analyses also revealed a significantly higher risk of developing pancreatic cancer in female patients with keloids compared to controls (Relative risk = 2.19) after adjustment for known pancreatic cancer risk factors. This study indicates that patients with keloids have a higher than normal risk for several cancer types, especially skin cancers (both genders) and pancreatic cancer (females). Therefore, patients with keloids should undergo regular skin examinations, and females with keloids should regularly undergo abdominal ultrasonography.

Correlation between the Nonperfusion Area on Ultra-Widefield Fluorescein Angiography and Nonflow Area on Optical Coherence Tomographic Angiography in Retinal Vein Occlusion.

AIMS: To compare the relationship between the nonperfusion area (NPA) on ultra-widefield fluorescein angiography (UWFFA) and the nonflow area (NFA) on optical coherence tomographic angiography (OCTA) in retinal vein occlusion (RVO). METHODS: Cross-sectional study. 46 eyes of 46 RVO patients who underwent UWFFA and OCTA. NPA and ischemic index (ISI) were quantified on UWWFA. NFA, vessel density (VD) of the superficial capillary plexus (SCP), the deep capillary plexus (DCP), and the size foveal avascular zone (FAZ) on 3 ∗ 3 mm OCTA were measured. The association of the NPA and ISI on UWWFA and the parameters on OCTA were analyzed. Spearman correlation was used for statistical testing. RESULTS: The NPA and ISI on UWFFA were significantly correlated with the NFA on OCTA in RVO, and r values were 0.688 (p < 0.01) and 0.680 (p < 0.01), respectively. VD in the SCP of the temporal quadrant was negatively correlated with NPA and ISI, and r values were -0.346 (p < 0.05) and -0.337 (p < 0.05), respectively. VD in the DCP of the temporal quadrant was negatively correlated with the NPA, and the r value was -0.246 (p < 0.05). No significant correlation was found between the NPA and ISI on UWFFA and VD of other quadrants in the SCP or DCP and the FAZ area on OCTA. CONCLUSION: NPA in the peripheral retina was correlated with NFA in macula. NFA detected by OCTA could be an indicator of the ischemic status in RVO.

Impact of Hepatoma-Derived Growth Factor Blockade on Resiniferatoxin-Induced Neuropathy.

Resiniferatoxin is an ultrapotent capsaicin analog that mediates nociceptive processing; treatment with resiniferatoxin can cause an inflammatory response and, ultimately, neuropathic pain. Hepatoma-derived growth factor, a growth factor related to normal development, is associated with neurotransmitters surrounding neurons and glial cells. Therefore, the study aims to investigate how blocking hepatoma-derived growth factor affects the inflammatory response in neuropathic pain. Serum hepatoma-derived growth factor protein expression was measured via ELISA. Resiniferatoxin was administrated intraperitoneally to induce neuropathic pain in 36 male Sprague-Dawley rats which were divided into three groups (resiniferatoxin+recombinant hepatoma-derived growth factor antibody group, resiniferatoxin group, and control group) (n = 12/group). The mechanical threshold response was tested with calibration forceps. Cell apoptosis was measured by TUNEL assay. Immunofluorescence staining was performed to detect apoptosis of neuron cells and proliferation of astrocytes in the spinal cord dorsal horn. RT-PCR technique and western blot were used to measure detect inflammatory factors and protein expressions. Serum hepatoma-derived growth factor protein expression was higher in the patients with sciatica compared to controls. In resiniferatoxin-group rats, protein expression of hepatoma-derived growth factor was higher than controls. Blocking hepatoma-derived growth factor improved the mechanical threshold response in rats. In dorsal root ganglion, blocking hepatoma-derived growth factor inhibited inflammatory cytokines. In the spinal cord dorsal horn, blocking hepatoma-derived growth factor inhibited proliferation of astrocyte, apoptosis of neuron cells, and attenuated expressions of pain-associated proteins. The experiment showed that blocking hepatoma-derived growth factor can prevent neuropathic pain and may be a useful alternative to conventional analgesics.

The association between keloid and osteoporosis: real-world evidence.

BACKGROUND: Keloids are characterized by disturbance of fibroblast proliferation and apoptosis, deposition of collagen, and upregulation of dermal inflammation cells. This benign dermal fibro-proliferative scarring condition is a recognized skin inflammation disorder. Chronic inflammation is a well-known contributor to bone loss and its sequelae, osteoporosis. They both shared a similar pathogenesis through chronic inflammation. We assessed whether keloids increase osteoporosis risk through using National Health Insurance Research Database. METHODS: The 42,985 enrolled patients included 8597 patients with keloids but no history of osteoporosis; 34,388 controls without keloids were identified from the general population and matched at a one-to-four ratio by age, gender. Kaplan-Meier method was applied to determine cumulative incidence of osteoporosis. Cox proportional hazard regression analysis was performed after adjustment of covariates to estimate the effect of keloids on osteoporosis risk. RESULTS: Of the 8597 patients with keloids, 178 (2.07%) patients were diagnosed with osteoporosis while in the 34,388 controls, 587 (1.71%) were diagnosed with osteoporosis. That is, the keloids patients had 2.64-fold higher risk of osteoporosis compared to controls after adjustment for age, gender, Charlson Comorbidity Index and related comorbidities. The association between keloids and osteoporosis was strongest in patients younger than 50 years (hazard ratio = 7.06%) and in patients without comorbidities (hazard ratio = 4.98%). In the keloids patients, a high incidence of osteoporosis was also associated with advanced age, high Charlson Comorbidity Index score, hyperlipidemia, chronic liver disease, stroke, and depression. CONCLUSIONS: Osteoporosis risk was higher in patients with keloids compared to controls, especially in young subjects and subjects without comorbidities.

Stroke and osteoporosis: a Taiwan cohort study.

BACKGROUND: Osteoporosis and stroke are major health problems that have potentially overlapping pathophysiological mechanisms. The aim of this study was to estimate osteoporosis risk in Taiwan patientswho had a stroke. METHOD: This study retrieved data contained in the Taiwan National Health Insurance Research Database for a population-based sample of consecutive patients either hospitalised for stroke or treated for stroke on an outpatient basis. A total of 7550 newly diagnosed patientswho had a stroke were enrolled during 1996-2010. Osteoporosis risk in these patients was then compared with a matched group of patients who had not had a stroke randomly selected from the database at a ratio of 1:4 (n=30 200). The relationship between stroke history and osteoporosis risk was estimated with Cox proportional hazard regression models. RESULTS: During the follow-up period, osteoporosis developed in 1537 patients who had a stroke and in 5830 patients who had not had a stroke. The incidence of osteoporosis for cohorts with and without stroke was 32.97 and 14.28 per 1000 person-years, respectively. After controlling for covariates, the overall risk of osteoporosis was 1.82-fold higher in the stroke group than in the non-stroke group. The relative osteoporosis risk contributed by stroke had apparently greater impact among male gender and younger age groups. CONCLUSION: History of stroke is a risk factor for osteoporosis in Taiwan. Much attention to stroke-targeted treatment modalities might minimise adverse outcomes of osteoporosis.

Nonmuscle Myosin II Activation Regulates Cell Proliferation, Cell Contraction, and Myofibroblast Differentiation in Keloid-Derived Fibroblasts.

Objective: Keloid is an abnormal scar that often develops in high-tension skin. It is caused by excessive fibroblast proliferation and collagen deposition. Nonmuscle myosin IIA (NM-IIA) is an important motor protein that regulates the mechanical transduction of cells. However, the role of NM-IIA in keloid pathogenesis remains unclear. Approach: NM-IIA expression was examined and compared in keloid skin and normal skin by immunofluorescence. The organization of smooth muscle actin (SMA)-mediated stress fibers in normal and keloid fibroblasts (NFs and KFs, respectively) were determined. Cell proliferation and cell contractility were measured in fibroblasts derived from normal and keloids. The NM-II pharmacological inhibitor (blebbistatin) and RNA interference were applied to block NM-IIA and investigate its regulatory role in SMA-mediated stress fibers, cell contractility, and cell proliferation after NM-IIA inhibition. Results: NM-IIA expression is increased in keloid tissue. Inhibition of NM-II by blebbistatin or targeting NM-IIA by RNA interference reduced transforming growth factor beta (TGF-ß)-mediated SMA-mediated stress fiber formation, cell proliferation, and cell contractility of NFs and KFs. Although TGF-ß failed to mediate phosphorylation of myosin light chain (pMLC, the activator of NM-II), pMLC can interact with SMA-mediated stress fiber. Finally, inhibition of NM-II by blebbistatin also reduced NF and KF proliferation after TGF-ß stimulation. Innovation: NM-IIA synergizes with TGF-ß to regulate fibroblast proliferation, contraction activity, and myofibroblasts differentiation. Conclusion: NM-IIA might be one of the therapeutic targets in keloids.

Quantification of Microvascular Density of the Optic Nerve Head in Diabetic Retinopathy Using Optical Coherence Tomographic Angiography.

AIMS: To quantify the capillary density of the optic nerve head in healthy control eyes and different stages of diabetic retinopathy (DR) eyes and identify the parameters to detect eyes with or without DR using optical coherence tomographic angiography (OCTA). METHODS: In this cross-sectional study, 211 eyes of 121 participants with type 2 diabetes with different stages of DR or without DR and 73 eyes of 38 healthy age-matched controls were imaged by OCTA. Radial peripapillary capillary (RPC) plexus density and retinal nerve fiber layer (RNFL) thickness were examined. The mixed model binary logistic regression model was used to identify the parameters to detect eyes with or without DR. The area under the receiver operating characteristic (ROC) curve was calculated. RESULTS: RPC density decreased significantly in diabetic patients without DR compared with the healthy controls, and it was negatively correlated with the severity of DR (P < 0.01). RPC density was a significant parameter to distinguish diabetic eyes with or without DR (P < 0.01). The area under the ROC curve was 0.743. CONCLUSIONS: Quantification of RPC density by OCTA provides evidence of microvascular changes in the optic nerve in diabetic patients. RPC density can serve as a possible biomarker in detecting eyes with DR. Larger cohort studies need to support this statement.