Exosomes derived from colorectal cancer cells take part in activation of stromal fibroblasts through regulating PHLPP isoforms.

Given that tumor cells primarily instigate systemic changes through exosome secretion, our study delved into the role of colorectal cancer (CRC)-secreted exosomal miR-224 in stromal reprogramming and its impact on endothelial cell angiogenesis. Furthermore, we assessed the potential clinical significance of a specific signature of circulating serum-derived miRNAs, serving as a non-invasive biomarker for CRC diagnosis. Circulating serum-derived miR-103a-3p, miR-135b-5p, miR-182-5p, and miR-224-5p were significantly up-regulated, while miR-215-5p, and miR-455-5p showed a significant down-regulation in CRC patients than in healthy individuals. Our findings indicated that the expressions of CAF-specific markers (α-SMA and FAP) and CAF-derived cytokines (IL-6, and SDF-1) were induced in fibroblasts stimulated with SW480 CRC exosomes, partly due to Akt activation. As a plausible mechanism, exosomal transfer of miR-224 from SW40 CRC cells may activate stromal fibroblasts, which in turn, may promote endothelial cell sprouting. The study identified PHLPP1 and PHLPP2 as direct targets of miR-224 and demonstrated that CRC-secreted exosomal miR-224 activates Akt signaling by regulating PHLPP1/2 in activated fibroblasts, thereby affecting the stromal cell proliferation and migration. This study established a panel of six-circulating serum-derived miRNAs as a non-invasive biomarker for CRC diagnosis. Also, we proposed a supporting model in which CRC-secreted exosomal miR-224 takes part in the stromal reprogramming to CAFs partly through regulating Akt signaling. This may affect the malignant biological behavior of activated stromal cells and thereby elicit a vascular response within the microenvironment of CRC cells. See also the graphical abstract(Fig. 1).

Optimal Adaptive Testing for Epidemic Control: Combining Molecular and Serology Tests.

Epidemic interventions based on surveillance testing programs are a fundamental tool to control the first stages of new epidemics, yet they are costly, invasive and rely on scarce resources, limiting their applicability. To overcome these challenges, we investigate two optimal control problems: (i) how testing needs can be minimized while maintaining the number of infected individuals below a desired threshold, and (ii) how peak infections can be minimized given a typically scarce testing budget. We find that in both cases the optimal testing policy for the well-known Susceptible-Infected-Recovered (SIR) model is adaptive, with testing rates that depend on the epidemic state, and leads to significant cost savings compared to non-adaptive policies. By using the concept of observability, we then show that a central planner can estimate the required unknown epidemic state by complementing molecular tests, which are highly sensitive but have a short detectability window, with serology tests, which are less sensitive but can detect past infections.

Comparison of gingival depigmentation with Er,Cr:YSGG laser and surgical stripping, a 12-month follow-up.

Gingival melanin hyperpigmentation is an esthetic concern for many individuals. In this study, we compared the standard surgical removal method with two different Er,Cr:YSGG laser settings in order to find the best treatment method. In 33 dental arches, the following three treatment groups were comparatively evaluated: (1) surgical stripping, (2) removal with laser setting 1 (4.5 W, 50 Hz, 100% water, 80% air, 60 µs, 800 µm Tip; MZ8), and (3) laser setting 2 (2.5 W, 50 Hz, 20% water, 40% air, 700 µs, 800 µm Tip; MZ8). We comparatively evaluated pain, patient satisfaction and wound healing, treatment time, and the amount of bleeding. Re-pigmentation was evaluated after 1 and 12 months by Hedin and Dummet pigmentation scores. Laser setting 1 had the best results regarding pain and patient satisfaction, although not statistically significant (P > 0.05). Wound healing results were better using lasers compared to surgical stripping (P < 0.05). Laser setting 1 was a faster procedure with mild amounts of bleeding. The least amount of bleeding was seen with laser setting 2. After 1 month, only two cases of the laser setting 2-treated areas showed an isolated pigmented area in the papilla; at 12 months, the mean Hedin indexes were still less than 2 and mean Dummett index less than 1 in all treatment techniques, with the lowest scores seen in the laser setting 1 sites. Based on our results, Er,Cr:YSGG laser can be more convenient for gingival depigmentation compared to surgical blade. Although not statistically significant, laser setting 1 with shorter pulse duration and higher water spray showed better overall results. However, laser setting 2, with longer pulse duration and less water spray, resulted in better coagulative effects and can be used to control bleeding wherever necessary in clinical practice.

Clinical effectiveness of low-level laser treatment on peripheral somatosensory neuropathy.

Peripheral sensory neuropathy treatment is one of the common treatment problems and causes morbidity and mortality in people suffering from that. Although treatment depends on the underlying cause of the condition, nevertheless, in some cases, there is no cure for it, and it requires palliative and symptomatic treatment. In laboratory studies, low-level laser has been effective in the nerves protection and restoration. The aim of this article is to investigate the clinical efficacy of low-level laser on improvement of the peripheral somatosensory neuropathy. Search in the articles published up to 30 October 2015 (full text and abstracts) in databases PubMed (Medline), Cochrane library, Physiotherapy Evidence Database was performed. The studies of low-level laser trials on patients with peripheral neuropathy were carried out and evaluated in terms of the exclusion criteria. There are 35 articles among which 10 articles had the intended and required criteria. 1, 3, and 6 articles study the patients with diabetes, neuropathy caused by trauma, and carpal tunnel syndrome, respectively. In six studies, laser led to a reduction in sensory impairment and improvement of the physiological function of the sensory nerves. In these articles, lasers (Diode, GaAlAs, He-Ne) had wavelength range 660-860 nm, radiation power 20-250 mW, energy density 0.45-70 J/cm2. The intervention sessions range was 6-21 times and patient follow-up was 0-6 months. According to the results of these studies, low-level laser therapy can improve sensory function in patients with peripheral somatosensory neuropathy, although little research have not been done, laser treatment regimens are varied and do not recommend a specific treatment protocol. It seems it requires more research to sum up better, particularly in relation to diabetes.

Posterolateral hip muscle strengthening versus quadriceps strengthening for patellofemoral pain: a comparative control trial.

OBJECTIVE: To compare the efficacy of posterolateral hip muscle strengthening versus quadriceps strengthening in reducing pain and improving health status in persons with patellofemoral pain (PFP). DESIGN: Comparative control trial. SETTING: Rehabilitation facility. PARTICIPANTS: Persons with a diagnosis of PFP (N=36; 18 men, 18 women). INTERVENTIONS: Patients were alternately assigned to a posterolateral hip muscle strengthening group (9 men and 9 women) or a quadriceps strengthening group (9 men and 9 women). The posterolateral hip muscle strengthening group performed hip abductor and external rotator strengthening exercises, whereas the quadriceps strengthening group performed quadriceps strengthening exercises (3 times a week for 8wk). MAIN OUTCOME MEASURES: Pain (visual analog scale [VAS]) and health status (Western Ontario McMaster Universities Osteoarthritis Index [WOMAC]) were assessed at baseline, postintervention, and 6-month follow-up. RESULTS: Significant improvements in VAS and WOMAC scores were observed in both groups from baseline to postintervention and baseline to 6-month follow-up (P<.001). Improvements in VAS and WOMAC scores in the posterolateral hip exercise group were superior to those in the quadriceps exercise group postintervention and at 6-month follow-up (P<.05). CONCLUSIONS: Although both intervention programs resulted in decreased pain and improved function in persons with PFP, outcomes in the posterolateral hip exercise group were superior to the quadriceps exercise group. The superior outcomes obtained in the posterolateral hip exercise group were maintained 6 months postintervention.

Life-threatening rhabdomyolysis following the interaction of two commonly prescribed medications.

We report an interaction between erythromycin and simvastatin resulting in life-threatening rhabdomyolysis in an elderly patient. Drugs that inhibit CYP3A4 enzyme can cause elevated serum levels of statins which amplifies the risk of statin-induced rhabdomyolysis. Physicians should be aware of potential drug interactions of statins, which are widely used in the community.

Effects of low-level He-Ne laser irradiation on the gene expression of IL-1beta, TNF-alpha, IFN-gamma, TGF-beta, bFGF, and PDGF in rat's gingiva.

Biostimulatory effects of laser irradiation on cell proliferation and wound healing has been reported. However, little is known about the molecular basis of the mechanism. Interleukin 1beta (IL-1beta), tumor necrotic factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) play an important role in inflammation, while platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta) and blood-derived fibroblast growth factor (bFGF) are the most important growth factors of periodontal tissues. The aim of this study was to investigate the effect of low-level He-Ne laser on the gene expression of these mediators in rats' gingiva and mucosal tissues. Twenty male Wistar rats were randomly assigned into four groups (A(24), A(48), B(24), B(48)) in which A(24) and A(48) were cases and B(24), B(48) were controls. An incision was made on gingiva and mucosa of the labial surface of the rats' mandibular incisors. Group A(24) was irradiated twice with 24 hours interval, while the inflamed tissues of group A(48) was irradiated three times with continuous He-Ne laser (632.8 nm) at a dose of 7.5 J/cm2 for 300 s. An energy of 5.1 J was given to the 68 mm(2) irradiation zone. Rats were killed 30 min after the last irradiation of case and control groups, then excisional biopsy was performed. Gene expression of the cytokines was measured using reverse transcriptase-polymerase chain reaction (RT-PCR) technique. Results were analyzed with Kruskal-Wallis and Mann-Whitney U tests. The gene expression of IL-1beta and IFN-gamma was significantly inhibited in the test groups (P < 0.05), while the gene expression of PDGF and TGF-beta were significantly increased (P < 0.05). The case and control groups did not have a significant difference in the gene expression of TNF-alpha and bFGF (P > 0.05). These findings suggest that low-level He-Ne laser irradiation decreases the amount of inflammation and accelerates the wound healing process by changing the expression of genes responsible for the production of inflammatory cytokines.