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Background: Treating postherpetic neuralgia (PHN), which is characterized with a long‐lasting lancinating mechanical allodynia or hyperalgesia, is a big challenge as it is hard to achieve complete resolution. A synthetic triterpenoid, CDDO (2‐cyano‐3,12‐dioxoolean‐1,9‐dien‐28‐oic acid) can exert pleiotropic effects including anti‐inflammation and neuroprotective activities. Nevertheless, the antinociceptive effect of CDDO and its derivatives remains unknown. Resiniferatoxin (RTX) is easily feasible, and an RTX‐treated rodent model can mimic the PHN‐like symptoms. Therefore, RTX‐treated rats were used to serve as a PHN rats' model in the study to elucidate whether a synthetic triterpenoid, CDDO, can improve mechanical allodynia in RTX‐treated rats. Methods: The antinociceptive effects of CDDO were assessed by behavioral tests, western blotting, and immunohistochemistry. Paw withdrawal mechanical threshold was determined using calibrated forceps. Results: Administration of RTX led to mechanical allodynia, neuronal cell death, and glial cell activation in the spinal cord of RTX‐treated rats. A synthetic triterpenoid, CDDO, blocked RTX‐induced mechanical allodynia, rescued neuronal cell death, and inhibited glial cell activation in the spinal cord of RTX‐treated rats. Conclusions: Our study provides a novel result that a synthetic triterpenoid, CDDO, can interfere neuronal cell death and glial cell activation in the spinal cord of RTX‐treated rats. Hence, CDDO is an alternative therapeutic choice for PHN. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate osteoporosis risk in atopic dermatitis (AD) patients. This study included patients in the Taiwan National Health Insurance Research dataset. The population-based study included all patients aged 20–49 years who had been diagnosed with AD during 1996–2010. In total, 35,229 age and gender-matched patients without AD in a 1:1 ratio were randomly selected as the non-AD group. Cox proportional-hazards regression and Kaplan–Meier analyses were used to measure the hazard ratios and the cumulative incidences of osteoporosis, respectively. During the follow-up period, 360(1.02%) AD patients and 127(0.36%) non-AD patients developed osteoporosis. The overall incidence of osteoporosis was4.72-fold greater in the AD patients compared to the non-AD patients (1.82 vs. 0.24 per 1,000 person-years, respectively) after adjusting for potential confounding factors. Osteoporosis risk factors included female gender, age, advanced Charlson Comorbidity Index, depression and use of corticosteroids. The dataset analysis showed that AD was significantly associated with subsequent risk of osteoporosis. [ABSTRACT FROM AUTHOR]

A novel degradable crosslinker, N, N′-bis(acryloyl) cystamine (BACy), was synthesized with cystamine dihydrochloride (Cy) and acryloyl chloride. Then three series of degradable thermosensitive hydrogels with different crosslinker contents were prepared from N-isopropyl acrylamide (NIPAAm), BACy (Bx-series) or N, N′-methylene-bis-acrylamide (NMBA)(Nx-series) or equimolar BACy and NMBA (BNx-series) as crosslinker, and diethoxyacetophenone (DEAP) as photoinitiator under UV-irradiation polymerization. The effect of crosslinker content on the properties of the hydrogels such as swelling behavior and mechanical properties was investigated. At the same time, their degradabilities were investigated by dissolving them into different concentrations of cysteine solution. The results show that the swelling ratios for the Bx-series hydrogels are lower than those for the Nx-series hydrogels. But, after degradation in the cysteine solution, the swelling ratios for the Bx-series hydrogels were greater than those for the Nx-series hydrogels. When the crosslinker content was increased, all values of shear stress (τ), shear modulus (G), and effective crosslinking density (ρX) increased. But, the ρX values for the reduced Bx series and BNx series hydrogels were lower than those for original hydrogels. Results also showed that the ρX values for the Nx series hydrogel were not affected by cysteine. The disulfide bonds of BACy in these novel hydrogels were decomposed (reduced) in the cysteine solution and converted into thiol group. These thiol groups could be used to absorb some metal ions such as silver ion. Hence, the absorption of silver ion for the hydrogel with thiol group was also investigated in this research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Cutaneous cryptococcosis usually develops secondary to hematogenous spread in immunocompromised hosts. Primary cutaneous cryptococcosis (PCC) is a rare condition characterized by localized skin eruptions and positive culture for Cryptococcus neoformans but without dissemination to the internal organs. Herein, we describe a typical case of PCC in an immunocompetent male who presented with a 1-month history of scattered erythematous indurated papules and plaques on his arm and without fever. The histology of his skin, tissue culture, and multiplex polymerase chain reaction (PCR) confirmed cutaneous cryptococcal infection by C neoformans var. neoformans. After extensive work-ups showed no evidence of systemic dissemination or underlying cellular-immunity deficiency, the diagnosis of primary cutaneous cryptococcosis was made. Treatment with fluconazole 400 mg daily for 14 days followed by 200 mg daily for another 14 days led to complete resolution of the skin lesions, and subsequent follow-up showed no signs of relapse. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

The article describes the case of a 78-year-old man who had an acquired digital fibrokeratoma (ADFK) of the finger. The patient presented with a nodule protruding from the medial side of the left second finger, which was successfully removed by liquid nitrogen cryotherapy. The types of ADFK as an uncommon tumor are also discussed.

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. [ABSTRACT FROM AUTHOR]

Objective: To study the expression and clinical significance of Bcl -2, BAG -1, Ki -67, ER and PR on premenopausal and postmenopausal endometrial polyps. Methods: The expression of Bcl-2, BAG-1, Ki-67, ER and PR in 30 cases premenopausal endometrial polyps and 30 cases postmenopausal endometrial polyps tissues were detected by immunohistochemistry. Results: Bcl-2, BAG-1 and Ki-67 were higher expression in endometrial polyps than control group (P< 0.05), but no signification difference among ER and PR expression(P>0.05). Ki-67 expression in postmenopausal endometrial polyps was significantly lower than premenopausal endometrial polyps tissues (P<0.05). There were no signification difference among Bcl-2, BAG-1, ER and PR expression between premenopausal and postmenopausal endometrial polyps (P>0.05). Correlation analysis showed that Ki-67 was positively correlated with PR on postmenopausal endometrial polyps (P<0.05), and there was no correlation among other groups (P>0.05). Conclusions: Bcl-2, BAG-1, Ki-67, ER and PR may play an important role at different period of endometrial polyps pathological changes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Stroke is a leading cause of death, morbidity and disability worldwide. Infection is a common complication in the acute phase after stroke. Herpes zoster is a common viral disease, in which the most debilitating complication is post-herpetic neuralgia, which can have a very large negative impact on quality of life. The aim of this study was to investigate whether stroke increases the risk of herpes zoster. Methods: This cohort study compared patients who had herpes zoster with and without a first incident of stroke. The Taiwan National Health Insurance Research Database was utilized to identify 20,551 stroke patients and 20,551 controls matched for age, gender, age categories and Charlson Comorbidity Index (CCI) score categories at a one-to-one ratio. Cox proportional-hazards regression models were employed to estimate herpes zoster risk in the stroke group relative to general population. Results: Compared to the control group, the stroke group had a greater risk for herpes zoster, especially within 1 year after stroke (adjust HR = 25.27). Both hemorrhagic stroke and ischemic stroke were significantly associated with herpes zoster (hemorrhagic type (IRR = 2.31, 95% CI, 1.67–3.20); ischemic type (IRR = 2.51, 95% CI 2.09–3.02)). However, the hemorrhagic stroke patients had a higher risk of herpes zoster ophthalmicus (IRR = 12.46, 95% CI 4.00–38.76) whereas the ischemic stroke patients had a higher risk of post-herpetic neuralgia (IRR = 2.24, 95% CI 1.56–3.20). Conclusion: Physicians should know about that adults with stroke have a higher than normal risk of herpes zoster. Thus, physicians must be acquainted with proper antiviral therapy and pain control to bring down the morbidity that ensues from herpes zoster. Use of herpes zoster vaccine may be considered in stroke patients. [ABSTRACT FROM AUTHOR]

Whether traumatic brain injury (TBI) is causally related to substance related disorder (SRD) is still debatable, especially in persons with no history of mental disorders at the time of injury. This study analyzed data in the Taiwan National Health Insurance Research Database for 19,109 patients aged ≥18 years who had been diagnosed with TBI during 2000–2010. An additional 19,109 randomly selected age and gender matched patients without TBI (1 : 1 ratio) were enrolled in the control group. The relationship between TBI and SRD was estimated with Cox proportional hazard regression models. During the follow-up period, SRD developed in 340 patients in the TBI group and in 118 patients in the control group. After controlling for covariates, the overall incidence of SRD was 3.62-fold higher in the TBI group compared to the control group. Additionally, patients in the severe TBI subgroup were 9.01 times more likely to have SRD compared to controls. Notably, patients in the TBI group were prone to alcohol related disorders. The data in this study indicate that TBI is significantly associated with the subsequent risk of SRD. Physicians treating patients with TBI should be alert to this association to prevent the occurrence of adverse events. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis and migraine are both important public health problems and may have overlapping pathophysiological mechanisms. The aim of this study was to use a Taiwanese population-based dataset to assess migraine risk in osteoporosis patients. Methods: The Taiwan National Health Insurance Research Database was used to analyse data for 40,672 patients aged ≥20 years who had been diagnosed with osteoporosis during 1996-2010. An additional 40,672 age-matched patients without osteoporosis were randomly selected as the non-osteoporosis group. The relationship between osteoporosis and migraine risk was estimated using Cox proportional hazard regression models. Results: During the follow-up period, 1110 patients with osteoporosis and 750 patients without osteoporosis developed migraine. After controlling for covariates, the overall incidence of migraine was 1.37-fold higher in the osteoporosis group than in the non-osteoporosis group (3.72 vs. 1.24 per 1000 person-years, respectively). Migraine risk factors included high Charlson Comorbidity Index score, female gender, hypertension, depression, asthma, allergic rhinitis, obesity, and tobacco use disorder. Conclusions: Our results indicate that patients with a history of osteoporosis had a higher risk of migraine. [ABSTRACT FROM AUTHOR]

The aims of this study were to investigate the risk of hip fracture and contributing factors in patients with erectile dysfunction(ED). This population-based study was performed using the Taiwan National Health Insurance Research Database. The analysis included4636 patients aged ≥ 40 years who had been diagnosed with ED (International Classification of Diseases, Ninth Revision, Clinical Modification codes 302.72, 607.84) during 1996–2010. The control group included 18,544 randomly selected age-matched patients without ED (1:4 ratio). The association between ED and hip fracture risk was estimated using a Cox proportional hazard regression model. During the follow-up period, 59 (1.27%) patients in the ED group and 140 (0.75%) patients in the non-ED group developed hip fracture. After adjusting for covariates, the overall incidence of hip fracture was 3.74-times higher in the ED group than in the non-ED group (2.03 vs. 0.50 per 1000 person-years, respectively). The difference in the overall incidence of hip fracture was largest during the 3-year follow-up period (hazard ratio = 7.85; 95% confidence interval = 2.94–20.96; P <0.0001). To the best of our knowledge, this nationwide population-based study is the first to investigate the relationship between ED and subsequent hip fracture in an Asian population. The results showed that ED patients had a higher risk of developing hip fracture. Patients with ED, particularly those aged 40–59 years, should undergo bone mineral density examinations as early as possible and should take measures to reduce the risk of falls. [ABSTRACT FROM AUTHOR]

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-1β 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]