Analgesic Effects of Two Types of Spinal Manipulation in Acute Lumbar Radiculopathy Model Rats.

OBJECTIVE: To compare the analgesic effects of two types of spinal manipulation (SM) in acute lumbar radiculopathy (ALR) model rats induced by self-transplantation of autologous nucleus pulposus (ANP), and clarify the therapeutic mechanism. METHODS: Totally 108 male Sprague-Dawley rats were randomly divided into 6 groups by a random number table (18 rats in each group), including a blank group with no interference, a sham operation group with a surgery by making a local soft tissue incision on the left side of L5-6 vertebral segment, a model group with ALR of L5 extraforaminal nerve by ANP self-transplantation without other interference, a sham manipulation (SMA) group with simulating physical rotation, as well as a mobilization (MOB) group with simulating low-velocity and variable-amplitude rotation and a manipulation (MAN) group with simulating high-velocity and low-amplitude rotation. The interventions in SMA, MOB, and MAN groups started 1 day after modeling followed by another 5 treatments at days 3, 5, 8, 10 and 12. Rats in the other 3 groups did not receive any special intervention. Behavioral pain tests of 50% mechanical pain withdrawal threshold (50% PWT) and paw withdrawal latency (PWL) were conducted 1 day before operation followed by another 10 tests on days 1-7, 10, 12 and 14. Immunohistochemical expression of nitric oxide synthase (NOS) was investigated on days 5 and 12 after operation. RESULTS: After 3 experimental SM interventions, 50% PWT and PWL were higher in the MAN group than the SMA group on days 6 and 7, and higher on days 10, 12 and 14 postoperatively (P<0.05 or P<0.01), while the same indices were significantly higher in the MOB group than MAN group on days 1-4 (P<0.05 or P<0.01). The expression of NOS was lower in the MAN and MOB groups than SMA group on day 12 postoperatively (P<0.01). CONCLUSIONS: Both manipulation and mobilization produced better results than sham interference in relieving pain by reducing neuroinflammation possibly. At the early period, compared with manipulation, mobilization presented less sensitive response to pain until later visit. SM may inhibit the overexpression of NOS, thereby alleviating severe radiculopathy.

Antifibrotic effects of Hypocrellin A combined with LED red light irradiation on keloid fibroblasts by counteracting the TGF-ß/Smad/autophagy/apoptosis signalling pathway.

Keloids are characterized by abnormal proliferation of fibroblasts and continuous deposition of extracellular matrix (ECM) components. In the field of dermopathy, photodynamic therapy (PDT) with visible light has been increasingly investigated. The natural photosensitizer Hypocrellin A (HA) was shown to have excellent light induced anticancer, antimicrobial and antiviral activities. In this experiment, we investigated the impacts of HA united light-emitting diode (LED) red light irradiation on human keloid fibroblast cells (KFs). Our results showed that HA combined with red light irradiation treatment (HA-R-PDT) decreased KF viability, reduced KF collagen production and ECM accumulation, inhibited cell proliferation, suppressed cell invasion and induced cell apoptosis. Moreover, our observations demonstrated that the TGF-ß/Smad signalling pathway and autophagy were restrained by HA-R-PDT. TGF-ß1 could promote autophagy in KFs through both the Smad and ERK pathways, while inhibition of autophagy altered the TGF-ß1 levels through negative feedback. Therefore, HA-R-PDT suppressed cell hyperproliferation, collagen synthesis and ECM accumulation of KFs by regulating the TGF-ß1-ERK-autophagy-apoptosis signalling pathway. HA-R-PDT deserves systematic investigation as a potential therapeutic strategy for keloids, and autophagy might be a promising candidate in the treatment of KFs.

Inhibition of ROS-NF-κB-dependent autophagy enhances Hypocrellin A united LED red light-induced apoptosis in squamous carcinoma A431 cells.

Cutaneous squamous cell carcinoma (cSCC) is a type of malignant skin tumor derived from epidermal Malpighian cells. Photodynamic therapy is regarded as a crucial method in oncology. Hypocrellin A (HA), an efficient natural photosensitizer, has been reported to exert excellent light induced antiviral, antimicrobial and anticancer activity through mediating multiple signaling pathways. The purpose of the present study is to examine the effects of HA united red light irradiation on human squamous carcinoma A431 cells and further reveal the underlying regulatory mechanisms. The results showed that synergistic treatment of HA and red light irradiation inhibited cell proliferation and induced cell apoptosis and autophagy. Moreover, HA united red light irradiation caused a significant accumulation of reactive oxygen species (ROS), and induced the activation of c-Jun NH 2 terminal kinases (JNKs) which was inhibited by the antioxidant N-Acetyl-cysteine (NAC). Furthermore, HA united red light irradiation activated the nuclear factor-kappa B (NF-κB) pathway, and inhibition of NF-κB activity exacerbated HA united red light irradiation-induced apoptosis but suppressed cell autophagy. In addition, the inhibition of autophagy promoted HA united red light irradiation-induced apoptosis and facilitated the NF-κB activity. Over all, our results revealed that HA united red light irradiation could inhibit A431 cell proliferation by inducing apoptosis and autophagy via the activation of the ROS mediated JNK and NF-κB pathways, providing prospective for HA as a potential therapeutic for the treatment of cSCC.

Inhibition of Autophagy Enhances Curcumin United light irradiation-induced Oxidative Stress and Tumor Growth Suppression in Human Melanoma Cells.

Malignant melanoma is the most aggressive form of skin carcinoma, which possesses fast propagating and highly invasive characteristics. Curcumin is a natural phenol compound that has various biological activities, such as anti-proliferative and apoptosis-accelerating impacts on tumor cells. Unfortunately, the therapeutical activities of Cur are severely hindered due to its extremely low bioavailability. In this study, a cooperative therapy of low concentration Cur combined with red united blue light irradiation was performed to inspect the synergistic effects on the apoptosis, proliferation and autophagy in human melanoma A375 cell. The results showed that red united blue light irradiation efficaciously synergized with Cur to trigger oxidative stress-mediated cell death, induce apoptosis and inhibit cell proliferation. Meanwhile, Western blotting revealed that combined disposure induced the formation of autophagosomes. Conversely, inhibition of the autophagy enhanced apoptosis, obstructed cell cycle arrest and induced reversible proliferation arrest to senescence. These findings suggest that Cur combined with red united blue light irradiation could generate photochemo-preventive effects via enhancing apoptosis and triggering autophagy, and pharmacological inhibition of autophagy convert reversible arrested cells to senescence, therefore reducing the possibility that damaged cells might escape programmed death.

Expression of glucocorticoid receptor-α in the epidermis of patients with psoriasis vulgaris.

Expression of glucocorticoid receptor (GR)-α is observed in almost all tissues and cells of the body; thus, investigating the expression of the receptor in the epidermis of patients with psoriasis vulgaris. The aim of the present study was to investigate GR-α expression in the epidermis of psoriasis vulgaris patients The study population consisted of 26 patients with psoriasis vulgaris and 10 normal control cases. None of the patients had received any prior treatment with glucocorticoids. Epithelial tissue samples were detected using a streptavidin peroxidation-enzymatic method for biopsy. Non-lesional tissue samples from within a range of 3 cm of lesions formed the non-lesional group, and lesional tissue samples formed the lesional group. Pathological image analysis system (named CMIAS) was used to convert image signals into numeric values, according to the optical density per unit area. GR-α expression was observed within the nucleus in the normal control group; however, cytoplasmic expression was observed in the lesions of the psoriatic group. The optical density values were significantly lower in the psoriatic group when compared with the normal control group, indicating a statistically significant difference in GR-α expression between the two groups (P<0.001), and this decreasing correlation was unaffected by the administration of steroids for 6 months. Therefore, decreased expression of GR-α may play an important role in the degeneration of keratinocytes in patients with psoriasis vulgaris.

The Protective Effect of Interleukin-37 on Vascular Calcification and Atherosclerosis in Apolipoprotein E-Deficient Mice with Diabetes.

Interleukin (IL)-37 is a newly discovered member of the cytokine IL-1 family. Recent evidence suggests that IL-37, an anti-inflammatory factor, may have a role in atherosclerosis. In this study we used apoE-deficient diabetic mice, an established animal model, to examine the effects of IL-37 on the progression of vascular calcification and atherosclerosis. Compared with the control groups, IL-37-treated (with injection of recombinant protein for 16 weeks) animals had significantly less calcification areas detected by both von Kossa and Alizarin Red staining, and much smaller plaque size of the atherosclerotic lesions and lower plaque vulnerability scores detected by hematoxylin-eosin staining in the aorta root. Our data also showed that IL-37 treatment caused elevated concentrations of osteoprotegerin (OPG) in serum. We detected that the group that received additional anti-OPG antibody reduced the effect of IL-37 treatment. The group that received both IL-37 and anti-OPG had significant larger percentage area of calcified lesion and atherosclerotic plaque size than the IL-37-treated group. Significant changes in disease-relevant cytokines (eg, ALP, BMP-2, TNF-α, IL-18, and IL-10) were also elicited. This is the first report that IL-37 could attenuate not only atherosclerosis, but also vascular calcification. This study may offer a therapeutic potential for the prevention and treatment of calcification and atherosclerotic disease.

[Effect of ileocecum interposition graft as pylorus replacement on glycometabolism].

OBJECTIVE: To evaluate the application of ileocecum interposition (ii) graft as pylorus replacement in alimentary reconstruction. METHODS: Twenty- one minipigs were randomly divided into three groups: sham operation group (control group), B - i group and ii group. The levels of blood glucose were measured by quick blood glucose testing of paper at 0, 30, 60, 90, and 120 minutes of oral glucose after 60 and 120 post- operative days to compare gastric emptying of liquid feeds. RESULTS: Two months after operation,the peak of blood glucose was (7.8+/- 1.0)mmol/ L, (7.1+/- 0.8)mmol/ L, (4.1+/- 0.4)mmol/ L in B - i, ii group and control group respectively, there were significant differences between the two operation groups and control group (P< 0.01). Four months after operation, the peak of blood glucose was (6.9+/- 1.0) mmol/ L, (5.2+/- 0.8)mmol/ L, (4.2+/- 0.5)mmol/ L, respectively, there was no significant difference between ii group and control group (P > 0.05),but there were significant differences between both of the above two groups and B - i group (P< 0.01). CONCLUSION: The ileocecum interposition graft can offer specific advantages over current reconstruction procedures.