Preparation of capsaicin-loaded ultrafine fiber film and its application in the treatment of oral ulcers in rats.

A drug-loaded diaphragm is an easy-to-use and effective drug delivery system that is often used to treat mouth ulcers. In this study, an ultrafine fiber film loaded with capsaicin was successfully prepared using the electrospinning technology. poly-L-lactic acid and gelatin were selected as the matrix materials to form the composite fiber, and trifluoroethanol was used as a co-solvent for poly-L-lactic acid, gelatin and capsaicin to prepare the spinning solution, which was simple to fabricate. The prepared fiber films were characterized based on their microscopic morphology and tested to derive their mechanical properties. Thereafter, the capsaicin release behavior of the film was investigated. In vitro experiments revealed certain anti-inflammatory and antibacterial abilities while animal experiments revealed that the capsaicin-loaded ultrafine fiber film could promote the healing of oral ulcers in rats. Healing of the tongue tissue in rats administered 10% capsaicin-loaded fiber film was found to be better than that in rats administered the commercial dexamethasone patch. Overall, this development strategy may prove to be promising for the development of oral ulcer patch formulations.

[Effect of ultrasonic curettage combined with sodium hyaluronate gel on chronic periodontitis and its effect on inflammatory factors hs-CRP, MCP-1 and MMP-13 in gingival crevicular fluid].

PURPOSE: To investigate the effect of ultrasonic curettage combined with sodium hyaluronate gel in the treatment of chronic periodontitis (CP) and the effect on inflammatory factor hypersensitive C-reactive protein (hs-CRP), monocyte chemotactic protein 1 (MCP-1) and matrix metalloproteinase 13 (MMP-13) in gingival crevicular fluid. METHODS: A total of 102 patients with CP from October 2021 to October 2022 were selected, divided into experimental group (n=51) and control group (n=51) by random number table method. The control group received ultrasonic subgingival curetage, and the experimental group received sodium hyaluronate gel adjuvant therapy on the basis of the control group. The periodontal rehabilitation indexes, clinical efficacy and the changes of gingival crevicular fluid hs-CRP, MCP-1 and MMP-13 were compared between the two groups. The periodontal pathogens, bone metabolism indexes and the occurrence of adverse events during treatment were compared between the two groups. The data were statistically analyzed using SPSS 22.0 software package. RESULTS: After treatment, the sulcus bleeding index (SBI), gingival index (GI), plaque index (PLI), periodontal pocket depth (PD) and attachment level (AL) of the two groups were significantly lower than before treatment (P＜0.05), and even significantly lower(P＜0.05) in the experimental group. Total effective rate of the experimental group was significantly higher than that of the control group(P＜0.05). hs-CRP, MCP-1 and MMP-13 in both groups after treatment were significantly lower than before treatment(P＜0.05), and hs-CRP, MCP-1 and MMP-13 in the experimental group after treatment were significantly lower than those in the control group(P＜0.05). The detection rates of Porphyromonas gingivalis, Forsetanella and Treponema dentalis were significantly lower in both groups after treatment than before treatment (P＜0.05), and the detection rates of the above indexes in the experimental group after treatment were significantly lower than those in the control group(P＜0.05). After treatment, the C-terminal peptide(CTX) of type Ⅰ collagen was significantly lower than that before treatment, and bone gla protein(BGP) was significantly higher than that before treatment(P＜0.05). The CTX and BGP of the experimental group were significantly lower than that of the control group and significantly higher than that of the control group(P＜0.05). There was no significant difference in the incidence of total adverse reactions between the two groups(P＞0.05). CONCLUSIONS：Ultrasonic curettage combined with sodium hyaluronate gel in the treatment of CP can promote periodontal tissue rehabilitation, enhance short-term efficacy, inhibit synthesis of inflammatory factors in gingival crevicular fluid, kill periodontal pathogens, regulate bone metabolism, and is safe and reliable.

Overexpression of DEL-1 Downregulates SH3BP2 Expression and Inhibits Porphyromonas gingivalis-induced Gingival Inflammation In Vivo and In Vitro.

PURPOSE: The role of developmental endothelial locus-1 (DEL-1) in Porphyromonas gingivalis (P. gingivalis)-induced periodontitis and the related molecular mechanisms are unclear. This study aimed to investigate the effect of DEL-1 on SH3 Domain Binding Protein 2 (SH3BP2) expression, and to explore the regulatory role of DEL-1 in periodontal inflammation. MATERIALS AND METHODS: We constructed a P. gingivalis-induced rat experimental periodontitis model, and cultured P. gingivalis-stimulated THP-1 cells in vitro. THP-1 cell viability and cell cycle were examined by CCK-8 and flow cytometry. Rat gingival tissues were collected for hematoxylin-eosin staining. The expression of SH3BP2 and nicotinamide phosphoribosyltransferase (NAMPT) was examined using Western blot. RESULTS: We found that the proliferation of P. gingivalis-infected THP-1 cells was increased by DEL-1. DEL-1 inhibited the expression of NAMPT and SH3BP2 in gingiva tissues of rats with periodontitis as well as in P. gingivalis-infected THP-1 cells. CONCLUSIONS: Overexpression of DEL-1 downregulated SH3BP2 expression and reduced gingival inflammation induced by P. gingivalis. DEL-1 presents some regulatory effects on gingival inflammation in a P. gingivalis-induced rat experimental periodontitis model, suggesting the therapeutic potential of DEL-1 in regulating periodontal inflammation.

Inhibitory effects of tetramethylpyrazine on pain transmission of trigeminal neuralgia in CCI-ION rats.

Tetramethylpyrazine (TMP) has anti-inflammatory effects and is used to treat cerebral ischemic injury, but the mechanism of TMP on neural protection is not clear. Trigeminal neuralgia (TN) is a facial pain syndrome that is characterized by paroxysmal, shock-like pain attacks located in the somatosensory distribution of the trigeminal nerve. P2X3 receptor plays a crucial role in facilitating pain transmission. The present study investigates the effects of TMP on trigeminal neuralgia transmission mediated by P2X3 receptor of the trigeminal ganglia (TG). Chronic constriction injury of the infraorbital branch of the trigeminal nerve (CCI-ION) was used as a trigeminal neuralgia model. On day 15 after surgery, there was a significant decline in the mechanical hyperalgesia threshold in the territory of the ligated infraorbital nerve in the TN group, and an increase in expression of P2X3 receptor in the TG of the TN group compared with the Sham group. After treatment with TMP or A-317491, the mechanical hyperalgesia threshold of TN rats was significantly higher, and expression of P2X3 receptor in the TG noticeably declined compared with the TN group. Phosphorylation of p38 and ERK1/2 in the TN group was stronger than in the Sham group. However, the phosphorylation of p38 and ERK1/2 in the TN+TMP group and TN+A-317491 group was much lower than in the TN group. TMP significantly inhibited the ATP activated currents in HEK293 cells transfected with a P2X3 plasmid. Thus, TMP might have inhibitory effects on trigeminal neuralgia by suppressing the expression of P2X3 receptor in the TG and the phosphorylation of p38 and ERK1/2 in the TG.

Peripheral glutamate receptors are required for hyperalgesia induced by capsaicin.

Transient receptor potential vanilloid1 (TRPV1) and glutamate receptors (GluRs) are located in small diameter primary afferent neurons (nociceptors), and it was speculated that glutamate released in the peripheral tissue in response to activation of TRPV1 might activate nociceptors retrogradely. But, it was not clear which types of GluRs are functioning in the nociceptive sensory transmission. In the present study, we examined the c-Fos expression in spinal cord dorsal horn following injection of drugs associated with glutamate receptors with/without capsaicin into the hindpaw. The subcutaneous injection of capsaicin or glutamate remarkably evoked c-Fos expression in ipsilateral sides of spinal cord dorsal horn. This capsaicin evoked increase of c-Fos expression was significantly prevented by concomitant administration of MK801, CNQX, and CPCCOEt. On the other hand, there were not any significant changes in coinjection of capsaicin and MCCG or MSOP. These results reveal that the activation of iGluRs and group I mGluR in peripheral afferent nerves play an important role in mechanisms whereby capsaicin evokes/maintains nociceptive responses.

Capsaicin-induced glutamate release is implicated in nociceptive processing through activation of ionotropic glutamate receptors and group I metabotropic glutamate receptor in primary afferent fibers.

Glutamate (Glu) is the major excitatory neurotransmitter in the central nervous system. The role of peripheral Glu and Glu receptors (GluRs) in nociceptive transmission is, however, still unclear. In the present study, we examined Glu levels released in the subcutaneous perfusate of the rat hind instep using a microdialysis catheter and the thermal withdrawal latency using the Plantar Test following injection of drugs associated with GluRs with/without capsaicin into the hindpaw. The injection of capsaicin into the rat hind instep caused an increase of Glu level in the s.c. perfusate. Capsaicin also significantly decreased withdrawal latency to irradiation. These effects of capsaicin were inhibited by pretreatment with capsazepine, a transient receptor potential vanilloid receptor 1 (TRPV1) competitive antagonist. Capsaicin-induced Glu release was also suppressed by combination with each antagonist of ionotropic GluRs (iGluRs: NMDA/AMPA receptors) and group I metabotropic GluR (mGluR), but not group II and group III mGluRs. Furthermore, these GluRs antagonists showed remarkable inhibition against capsaicin-induced thermal hyperalgesia. These results suggest that Glu is released from the peripheral endings of small-diameter afferent fibers by noxious stimulation and then activates peripheral iGluRs and group I mGluR in development and/or maintenance of nociception. Furthermore, the activation of peripheral NMDA/AMPA receptors and group I mGluR may be important in mechanisms whereby capsaicin evokes nociceptive responses.