Microglial functions are linked to Ca²⁺ signaling, with endoplasmic reticulum (ER) calcium stores playing a crucial role. Microglial abnormality is a hallmark of Alzheimer's disease (AD), but how ER Ca²⁺ receptors regulate microglial functions under physiological and AD conditions remains unclear. We found reduced ryanodine receptor 2 (Ryr2) expression in microglia from an AD mouse model. Modulation of RyR2 using S107, a RyR-Calstabin stabilizer, blunted spontaneous Ca²⁺ transients in controls and normalized Ca²⁺ transients in AD mice. S107 enhanced ATP-induced migration and phagocytosis while reducing ramification in control microglia; however, these effects were absent in AD microglia. Our findings indicate that RyR2 stabilization promotes an activation state shift in control microglia, a mechanism impaired in AD. These results highlight the role of ER Ca²⁺ receptors in both homeostatic and AD microglia, providing insights into microglial Ca²⁺ malfunctions in AD.
Animals ; Microglia/pathology* ; Alzheimer Disease/pathology* ; Phagocytosis/drug effects* ; Ryanodine Receptor Calcium Release Channel/metabolism* ; Disease Models, Animal ; Mice ; Cell Movement/drug effects* ; Mice, Transgenic ; Calcium Signaling/physiology* ; Calcium/metabolism* ; Mice, Inbred C57BL ; Male ; Endoplasmic Reticulum/metabolism*

Objective To evaluate the efficacy and toxicity of induction chemotherapy with nedaplatin and docetaxel plus concurrent intensity?modulated radiotherapy ( IMRT) with nedaplatin or cisplatin in the treatment of locally advanced nasopharyngeal carcinoma (NPC). Methods A total of 223 patients with pathologically diagnosed locally advanced NPC in five treatment centers from 2011 to 2012 were randomly divided into two groups. In the test group, one hundred and thirteen patients received two cycles of induction chemotherapy with docetaxel (65 mg/ m2 on day 1) and nedaplatin (80 mg/ m2 on day 1) plus concurrent IMRT with nedaplatin (40 mg/ m2 on day 1). In the control group, 110 patients received two cycles of induction chemotherapy with the same regimens plus concurrent IMRT with cisplatin (40 mg/ m2 on day 1). The survival rates were calculated with the Kaplan?Meier method and the differences in the survival rates between the two groups were analyzed using the log?rank test. Comparison of the incidence rates of adverse reactions between the two groups was made by the chi?square test. Results The follow?up rate was 99?? 1%.The response rates at 3 months after treatment in the two groups were both 100%. The 2?year local recurrence?free, regional recurrence?free, distant metastasis?free, and overall survival rates were 94?? 0%, 94?? 2%, 88?? 2%, and 90?? 3%, respectively, in the test group, versus 93?? 4%, 94?? 1%, 86?? 7%, and 87?? 3% in the control group ( P= 0?? 757、 0?? 478、 0?? 509、 0?? 413). The incidence rates and severity of leucopenia, neutropenia, and thrombocytopenia were significantly higher in the test group than in the control group ( P= 0?? 027 , 0?? 028 , 0?? 035 ) . The incidence rates and severity of hemoglobin reduction and nausea /vomiting were significantly lower in the test group than in the control group (P= 0?? 000,0?? 023). There were no significant differences in the incidence rates of mucositis and xerostomia between the two groups ( P=0?? 483,0?? 781). Conclusions The short?term efficacy of induction chemotherapy with nedaplatin and docetaxel plus concurrent IMRT with nedaplatin is similar to that with cisplatin in the treatment of locally advanced NPC. The mild gastrointestinal reactions can be tolerated by patients. However, the severe myelosuppression should be closely monitored during the treatment.

Objective: To observe the effects of needles with different diameters on the gastrointestinal function in mice. Methods: Eighteen Kunming mice were randomly divided into group of 0.25 mm needle, group of 0.35 mm needle, and control group. The acupoint of Zusanli (ST 36) was needled once a day for 5 days. The effects of needles with different diameters were observed by measuring the distance of the carbon moved in the intestine. Results: The distance of the carbon moved in the intestine was longer in the acupuncture group than in the control group (P<0.05), and it was longer in the group of 0.35 mm needle than in the group of 0.30 mm needle, there was no significant difference (P>0.05). Conclusion: Acupuncture treatment can enhance the peristalsis function of stomach and intestine in mice. The diameter of needle has no effect on the gastrointestinal function.

Objective To investigate the role of substance P (SP) and its neurokinin-1 receptor (NK-1R) in the pathophysiologic process of Crohn′s disease. Methods In 23 surgical patients of Crohn′s disease and 24 healthy controls, reverse transcription polymerase chain reaction (RT-PCR) was used to determine the mRNA expression of NK-1R, Western blot analysis was used to determine NK-1R protein expression levels, and immunohistochemistry was used to localize expression of NK-1R. Results Compared with normal gut NK-1R mRNA and NK-1R protein in Crohn′s disease were overexpressed. In Crohn′s disease moderate to strong intestinal NK-1R immunoreactivity was found in the lamina propria mononuclear cells, lymphoid follicles, and the surface and crypt epithelium, lymphoid follicles, submucosal vessels, smooth muscle and myoenteric plexus neurones. Conclusions In cases of Crohn′s disease, overexpression of NK-1R may disturb neuropeptides loop balance, and may be involved in the pathophysiological change in this disease.