Effects of Tibetan medicine Longdan zhike tablet on chronic obstructive pulmonary disease through MAPK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Longdan zhike tablet (LDZK) is a Tibetan medicine formula commonly used in the highland region of Tibet, China, to ameliorate respiratory diseases, such as acute bronchitis and asthma. In Chinese traditional medicine, some herbal formulas with anti-inflammatory properties targeting the respiratory system are clinically adopted as supplementary therapies for chronic obstructive pulmonary disease (COPD). However, the specific anti-COPD effects of LDZK remain to be evaluated. AIM OF THE STUDY: The aim of this study is to identify the principal bioactive compounds in LDZK, and elucidate the effects and mechanisms of the LDZK on COPD. METHODS: High-resolution mass spectrometry was utilized for a comprehensive characterization of the chemical composition of LDZK. The therapeutic effects of LDZK were assessed on the LPS-papain-induced COPD mouse model, and LPS-induced activation model of A549 cells. The safety of LDZK was evaluated by orally administering a single dose of 30 g/kg to rats and monitoring physiological and biochemical indicators after a 14-day period. Network pharmacology and Western blot analysis were employed for mechanism prediction of LDZK. RESULTS: A comprehensive analysis identified a total of 45 compounds as the major constituents of LDZK. Oral administration of LDZK resulted in notable ameliorative effects in respiratory function, accompanied by reduced inflammatory cell counts and cytokine levels in the lungs of COPD mice. Acute toxicity tests demonstrated a favorable safety profile at a dose equivalent to 292 times the clinically prescribed dose. In vitro studies revealed that LDZK exhibited protective effects on A549 cells by mitigating LPS-induced cellular damage, reducing the release of NO, and downregulating the expression of iNOS, COX2, IL-1ß, IL-6, and TNF-α. Network pharmacology and Western blot analysis indicated that LDZK primarily modulated the MAPK signaling pathway and inhibited the phosphorylation of p38/ERK/JNK. CONCLUSIONS: LDZK exerts significant therapeutic effects on COPD through the regulation of the MAPK pathway, suggesting its potential as a promising adjunctive therapy for the treatment of chronic inflammation in COPD.

Attenuated regenerative properties in human periodontal ligament-derived stem cells of older donor ages with shorter telomere length and lower SSEA4 expression.

Periodontal ligament (PDL) stem cell properties are critical in the periodontal tissue regeneration for periodontitis. Previously, we have demonstrated that cigarette smoking attenuates PDL-derived stem cell (PDLSC) regenerative properties. Here, we report the findings on the regenerative properties of human PDLSCs with different donor ages and the underlying mechanisms. Human PDLSCs from 18 independent donors were divided into different age groups (≤ 20, 20-40, and > 40 years old). The proliferation of PDLSCs with donor age of ≤ 20 years old was significantly higher than that of the 20-40- and > 40-years-old groups, whereas the migration of PDLSCs with donor age of ≤ 20 and 20-40 years old was significantly higher than that of the > 40-years-old group. Moreover, the mesodermal lineage differentiation capabilities of PDLSCs were also higher in the donor age group of ≤ 20 years old than the donor age of > 40 years old. In addition, shorter telomere length and lower expression of SSEA4 were found in PDLSCs with donor age of > 40 years old, compared with those with donor age of ≤ 20-years-old group. Besides, PDLSCs with donor age of 20-40 and > 40 years old had higher IL6 and CXCL8 gene expressions. In summary, results from this study revealed the attenuated proliferation, migration, and mesodermal lineage differentiation properties in human PDLSCs with older donor ages. Donor age of PDLSCs should be considered as the selection criteria for the periodontal tissue regeneration treatment.

Expression of NF-κB in oral squamous cell carcinoma and paracancerous tissues and its significance / 口腔疾病防治

Objective@#To investigate the expression and significance of NF-κB in oral squamous cell carcinoma and paracancerous tissues.@*Methods@# Cancerous and paracancerous tissues about 5 mm outside the tumor boundary were cut from 47 patients with OSCC. NF-κB expression in these tissues were detected by the immunohistochemical SP method and compared with that in 32 normal oral mucosa tissues. @*Results @# The average optical density (OD value) of immunohistochemical-positive cells in cancer tissues and paracancerous tissues was higher than that in normal tissues, and the difference was statistically significant (P < 0.001). There was no significant difference in the OD values between cancer tissues and paracancerous tissues (P=0.356). The rate of NF-κB positive expression in cancer tissue and paracancerous tissue was significantly higher than that in normal mucosa tissue, and the difference was statistically significant (P < 0.001). There was no significant difference in the rate of NF-κB positive expression between cancer tissues and paracancerous tissues (P=0.117), but the rate of moderate-to-strong positive expression in cancer tissues was significantly higher than that in paracancerous tissues (P < 0.001).@*Conclusion@# NF-κB may be involved in the development of OSCC.

Human Periodontal Ligament-Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration After Optic Nerve Injury.

Optic neuropathies are the leading cause of irreversible blindness and visual impairment in the developed countries, affecting more than 80 million people worldwide. While most optic neuropathies have no effective treatment, there is intensive research on retinal ganglion cell (RGC) protection and axon regeneration. We previously demonstrated potential of human periodontal ligament-derived stem cells (PDLSCs) for retinal cell replacement. Here, we report the neuroprotective effect of human PDLSCs to ameliorate RGC degeneration and promote axonal regeneration after optic nerve crush (ONC) injury. Human PDLSCs were intravitreally injected into the vitreous chamber of adult Fischer rats after ONC in vivo as well as cocultured with retinal explants in vitro. Human PDLSCs survived in the vitreous chamber and were maintained on the RGC layer even at 3 weeks after ONC. Immunofluorescence analysis of ßIII-tubulin and Gap43 showed that the numbers of surviving RGCs and regenerating axons were significantly increased in the rats with human PDLSC transplantation. In vitro coculture experiments confirmed that PDLSCs enhanced RGC survival and neurite regeneration in retinal explants without inducing inflammatory responses. Direct cell-cell interaction and elevated brain-derived neurotrophic factor secretion, but not promoting endogenous progenitor cell regeneration, were the RGC protective mechanisms of human PDLSCs. In summary, our results revealed the neuroprotective role of human PDLSCs by strongly promoting RGC survival and axonal regeneration both in vivo and in vitro, indicating a therapeutic potential for RGC protection against optic neuropathies. Stem Cells 2018;36:844-855.

Clinical report and literature review on the amyloidosis of salivary glands / 口腔疾病防治

@#Amyloidosis of salivary glands is a rare disease. The case of a 62-year-old male patient with 20 years of progressive swelling of the floor of the mouth and raising of the tongue that impacted the swallowing, phonation, and tongue movement of the patient is reported in this paper. Clinical examination revealed a large mass in the floor of the mouth. The lip and cheek mucosae had a considerable number of hard, soybean-sized, light-yellow nodules. The surgical removal of the mass under and in front of the tongue was performed. A pathology examination and Congo red staining confirmed the diagnosis of amyloidosis of the submandibular glands and sublingual glands. No recurrence was observed after 5 years of follow-up. The literature on the relevant problems was reviewed.

Analysis of Helicobacter pylori infection in patients with oral lichen planus / 口腔疾病防治

Objective @#To explore the correlation between oral mucosal lichen planus and Helicobacter pylori infection by analyzing the infection status of Helicobacter pylori in patients with oral mucosal lichen planus.@*Methods@#14C- urea breath test was done in 69 patients with oral lichen planus and 28 patients with chronic inflammation of oral mucosa. Detection of serum anti Helicobacter pylori antibody was done in 32 patients (23 with oral lichen planus and 9 with chronic inflammation of oral mucosa) at the same time. @*Results @#The positive rate of 14C-urea breath test was 68.12% in patients with oral lichen planus and 46.43% in chronic inflammation of oral mucosa. There was significant difference between the 2 groups (χ2=3.970, P=0.046). The positive rate of anti Helicobacter pylori antibody was 52.17% in patients with oral lichen planus and 22.22% in chronic inflammation of oral mucosa, and there was no significant difference between the 2 groups (χ2=2.358, P=0.125). @*Conclusion @#The prevalence of Helicobacter pylori infection in patients with oral lichen planus is higher, and there is a relevance between oral lichen planus and Helicobacter pylori infection.

Extracapsular dissection of the upper part of parotid gland benign tumor using a tragus edge combined retroauticular hairline incision approach / 口腔疾病防治

Objective@#To investigate the clinical effect of dissection in the upper part of parotid gland benign tumor using a tragus edge combined retroauticular hairline incision approach.@*Methods@#20 cases of upper part of parotid gland benign tumor were resected using the tragus edge combined retroauticular hairline incision approach, the surgery and cosmetic effect were analyzed. @*Results@#Parotid gland tumors were checked by CT before the operation and diagnosed by frozen section analysis during the operation. The tumors were successfully complete resected in all cases. There were no complications of Frey’s syndrome, postoperative bleeding, and flap necrosis, 2 cases showed a temporary earlobe numbness, 1 case of temporary facial nerve paralysis and 1 case of salivary fistula. There were no tumor recurrence after 24 ~ 48 months followed up. Surgical incision cosmetic effect is satisfactory. @*Conclusion@#The tragus edge combined retroauticular hairline incision is safe and feasible, with less complications for the upper part of parotid gland benign tumor resecetion.

Directing adult human periodontal ligament-derived stem cells to retinal fate.

PURPOSE: To investigate the retinal fate competence of human postnatal periodontal ligament (PDL)-derived stem cells (PDLSC) through a directed differentiation mimicking mammalian retinogenesis. METHODS: Human teeth were collected from healthy subjects younger than 35 years old. Primary PDLSC were isolated by collagenase digestion and cultivated. PDLSC at passage 3 were cultured in the induction media containing Noggin (antagonist of bone morphogenic protein) and Dkk-1 (antagonist of Wnt/ß-catenin signaling). Gene expression of neural crest cells, retinal progenitors, and retinal neurons, including photoreceptors, was revealed by RNA analyses, immunofluorescence, and flow cytometry. The neuronal-like property of differentiated cells in response to excitatory glutamate was examined by fluo-4-acetoxymethyl calcium imaging assay. RESULTS: Primary human PDLSC stably expressed marker genes for neural crest (Notch1, BMP2, Slug, Snail, nestin, and Tuj1), mesenchymal stem cell (CD44, CD90, and vimentin), and embryonic stem cell (c-Myc, Klf4, Nanog, and SSEA4). Under low attachment culture, PDLSC generated neurospheres expressing nestin, p75/NGFR, Pax6, and Tuj1 (markers of neural progenitors). When neurospheres were plated on Matrigel-coated surface, they exhibited rosette-like outgrowth. They expressed eye field transcription factors (Pax6, Rx, Lhx, Otx2). By flow cytometry, 94% of cells were Pax6(nuclear)Rx(+), indicative of retinal progenitors. At prolonged induction, they expressed photoreceptor markers (Nrl, rhodopsin and its kinase) and showed significant responsiveness to excitatory glutamate. CONCLUSIONS: Primary human PDLSC could be directed to retinal progenitors with competence for photoreceptor differentiation. Human neural crest-derived PDL is readily accessible and can be an ample autologous source of undifferentiated cells for retinal cell regeneration.