Sigma-1 Receptor and Binding Immunoglobulin Protein Interact with Ulinastatin Contributing to a Protective Effect in Rat Cerebral Ischemia/Reperfusion.

OBJECTIVE: To investigate impact of ulinastatin (UTI) on sigma-1 receptor (σ1R) and binding immunoglobulin protein (BiP) after cerebral ischemia/reperfusion injury. METHODS: The middle cerebral artery occlusion (MCAO) model was used to induce cerebral ischemia/reperfusion injury. Eighty male Sprague Dawley rats were randomly divided into 6 groups: control, MCAO, MCAO+50,000 U/kg UTI, MCAO+100,000 U/kg UTI, MCAO+200,000 U/kg UTI, MCAO+300,000 U/kg UTI. At 24 and 48 hours after MCAO, infarct volume, neurological dysfunction, and grip strength test were measured, and level of σ1R and BiP proteins was further detected using Western blot. Molecular docking assays were carried out to verify interaction between σ1R, BiP, and UTI. The serum concentration of BiP and the binding assay between σ1R, BiP, and UTI were determined using enzyme-linked immunosorbent assay. RESULTS: UTI increased the modified neurological severity score and upregulated σ1R and BiP expression in the cerebral cortex after MCAO. The grip strength of forelimbs increased significantly in the MCAO+200,000 U/kg UTI and MCAO+300,000 U/kg UTI groups compared with the MCAO group, while BiP serum levels remained unchanged. The molecular docking assay indicated putative binding between σ1R, BiP, and UTI. The binding assay also revealed that both σ1R and BiP could be combined with UTI. CONCLUSIONS: UTI displays a neuroprotective effect via upregulation of σ1R and BiP during ischemia/reperfusion injury, suggesting that UTI modulates σ1R and BiP and their interaction may provide a novel insight into potential therapeutic mechanisms for stroke.

Insight Into the Molecular Mechanism of Podophyllotoxin Derivatives as Anticancer Drugs.

Podophyllotoxin (PTOX) is a biologically active compound derived from the podophyllum plant, and both it and its derivatives possess excellent antitumor activity. The PTOX derivatives etoposide (VP-16) and teniposide (VM-26) have been approved by the U.S. Food and Drug Administration (FDA) for cancer treatment, but are far from perfect. Hence, numerous PTOX derivatives have been developed to address the major limitations of PTOX, such as systemic toxicity, drug resistance, and low bioavailability. Regarding their anticancer mechanism, extensive studies have revealed that PTOX derivatives can induce cell cycle G2/M arrest and DNA/RNA breaks by targeting tubulin and topoisomerase II, respectively. However, few studies are dedicated to exploring the interactions between PTOX derivatives and downstream cancer-related signaling pathways, which is reasonably important for gaining insight into the role of PTOX. This review provides a comprehensive analysis of the role of PTOX derivatives in the biological behavior of tumors and potential molecular signaling pathways, aiming to help researchers design and develop better PTOX derivatives.

[Uprighting a mesially tilted mandibular second molar by using a dental implant as anchorage: a case report].

After tooth has been removed for a long time, adjacent teeth may tilt to occupy the edentulous space, leading to a break in the occlusal 3D equilibrium and a lack of restorative space. This case report presents a mandibular second molar uprighting with anchorage from a dental implant.

[Suggestions for selection and use of masks for dental medical staff during outbreaks of novel coronavirus pneumonia].

During the outbreak of novel coronavirus pneumonia (NCP), dentists are at risk for more severe infection due to their professionalism. This article analyzed the route of infection during diagnosis and treatment of oral diseases. Following the related standards and guidelines of National Health Commission, the types, evaluation index and standards of medical and protective masks were summarized. It is expected to provide certain reference for the selection and use of masks of dental medical staff.

Comparison of clinical efficacy between robotic-laparoscopic excision and traditional laparoscopy for rectal cancer: A protocol for systematic review and meta-analysis.

BACKGROUNDS: Laparoscopic surgery, robot-assisted surgery and open surgery are the most commonly consumed surgical techniques in daily living. Considering that in recent years, the situation of choosing laparoscopic surgery and robot-assisted surgery to treat rectal cancer in China is prosperous. Meanwhile, researches lacked in the comparison part between the 2, so we will systematically compare the clinical efficacy of robot-assisted resection and traditional laparoscopic resection for rectal cancer. METHODS AND ANALYSIS: We will search Clinical research literature published before January 2020 in PubMed, Embase, the Cochrane library, Science Network, Wan Fang database, Chinese national knowledge infrastructure, and Chinese biomedicine that evaluate the correlation of rectal cancer with Leonardo's robot and traditional laparoscopy, from inception to July 2019. Weighted mean difference and odds ratio were used to compare the efficacy of robot-assisted resection versus conventional laparoscopic resection for rectal cancer, and the main indicators are operation time, complication rate, conversion rate, blood loss, and length of stay. RESULTS AND CONCLUSION: This study will systematically evaluate the clinical efficacy of robot-assisted resection and traditional laparoscopic resection for rectal cancer, thus providing evidence to the clinical application. The results will be published in a peer-reviewed journal. ETHICS AND DISSEMINATION: No ethical approval and participant consent are required, since this study data is based on published literature. The results of the study will be submitted to a peer-reviewed journal.PROSPERO registration number: CRD42020172161.

Light stimulus responsive nanomedicine in the treatment of oral squamous cell carcinoma.

Light stimulus responsive therapies are based on a variety of low-toxic therapeutic agents and produce anti-tumor effects only under external light stimulation, thus greatly reducing system toxicity and improving the specificity of treatment. Moreover, light stimulus responsive drug delivery system (DDS) can combine various theranostics molecules to exert synergistic therapeutic effects of various treatments, which has played an important role in cancer treatment. In this review, we introduced the light stimulus responsive cancer therapies including photodynamic therapy (PDT), photothermal therapy (PTT) and light-triggered DDS applied in the treatment of OSCC, described considerable photosensitizers (PSs) and nanomaterials used for oral cancers, which will hope to better the clinic outcome of OSCC patients.

Susceptibility of Multiple Primary Cancers in Patients With Head and Neck Cancer: Nature or Nurture?

Multiple primary cancers (MPCs) are major obstacles to long-term survival in head and neck cancer (HNSCC), however, the molecular mechanism underlying multiple carcinogenesis remains unclear. "Field cancerization" is a classical theory to elaborate the malignant progression of MPCs. Apart from environmental and immune factors, genetic factors may have great potential as molecular markers for MPCs risk prediction. This review focuses on inherited and acquired gene mutations in MPCs, including germ-line mutation, single-nucleotide polymorphism, chromosomal instability, microsatellite instability and DNA methylation. And definition and prognosis of MPCs have also been discussed. These may pave the way for the early detection, prevention and effective treatment of MPCs in HNSCC.

[Minimal invasive microscopic tooth preparation based on endodontic, periodontal and functional health].

Tooth preparation is the primary and core operation technique for dental esthetic restoration treatment, due to its effect of providing restoration space, bonding interfaces and marginal lines for dental rehabilitation after tooth tissue reduction. The concept of microscopic minimal invasive dentistry put forward the issue of conducting high-quality tooth preparation, conserve tooth-structure, protect vital pulp and periodontal tissue simultaneously. This study reviewed the concepts, physiology background, design and minimal invasive microscopic tooth preparation, and in the meantime, individualized strategies and the two core elements of tooth preparation (quantity and shape) are listed.

Functions of chemokines in the perineural invasion of tumors (Review).

The perineural invasion (PNI) of malignant tumors is a form of tumor progression in which cancer cells encroach along nerves. PNI hinders curative resection. Residual tumor cells in or around nerves can bring about local recurrence, infiltration and metastasis. This behavior is usually associated with a poor clinical prognosis. Therefore, it is necessary to investigate novel ligand-receptor crosstalk between nerves and tumor cells that promote the process of PNI. Chemokines are regarded as one of pivotal factors involved in the process of PNI. The present review collates information provided by previous studies with regard to the role of chemokines in PNI. The study presents a definition of PNI in cancer, generalizes the biological characteristics and the expression of chemokines and their receptors in cancer types associated with PNI, and discusses the underlying molecular mechanisms of chemokines, the reciprocal interactions between chemokines and other factors in PNI, and the interconnectivity of the microenvironment and chemokines. The aim of the review is to thoroughly illustrate the molecular cues of chemokines in cancer with PNI and to identify novel antitumor targets.

Micromotions and combined damages at the dental implant/bone interface.

Micromotion and fretting damages at the dental implant/bone interface are neglected for the limitation of check methods, but it is particularly important for the initial success of osseointegration and the life time of dental implant. This review article describes the scientific documentation of micromotion and fretting damages on the dental implant/bone interface. The fretting amplitude is less than 30 µm in vitro and the damage in the interface is acceptable. While in vivo, the micromotion's effect is the combination of damage in tissue level and the real biological reaction.

Involvement of Wnt activation in the micromechanical vibration-enhanced osteogenic response of osteoblasts.

BACKGROUND: Low-magnitude vibration has been widely used as a tool for rehabilitation, enhancing physical performance, and stimulating bone development. Although mechanical stimulation generated by vibrations is regarded as important factor in bone remodeling, the underlying cellular and molecular regulatory mechanisms of this response, which may be important in the development of new mechanobiological strategies, currently remain unclear. METHODS: In this study, to investigate the mechanobiological mechanisms of vibration-enhanced osteogenic responses in osteoblasts, MC3T3-E1 cells were subjected to vibrations of different amplitude (0.06, 0.14, 0.32, 0.49, 0.66, and 0.8 × g) at 40 Hz for 30 min/day over 3 days. The osteogenesis-related transcription factors Wnt10B, Sclerostin, OPG, and RANKL were analyzed for mRNA and protein expression. RESULTS: The results revealed that protein expression of Wnt10B and OPG was increased in a magnitude-dependent manner by mechanical vibrations at amplitudes of 0.06, 0.14, 0.32, and 0.49 × g; the maximum increases were 2.4-fold (p < 0.001) and 7.9-fold (p < 0.001), respectively, at 0.49 × g. Sclerostin and RANKL levels were reduced at all amplitudes. On the basis of mRNA levels, the reduced expression of RANKL was further downregulated (p < 0.05) whereas OPG expression was further increased (p < 0.01) when the MC3T3-E1 cells were treated with LiCl compared with the effects of vibration alone. CONCLUSIONS: The findings may indicate that Wnt signaling is involved in mechanotransduction at low-magnitude vibration; this may provide a cellular basis, and impetus for further development of, biomechanically based intervention for enhancing bone strength and accelerating implant osseointegration.

Reciprocal roles between caffeine and estrogen on bone via differently regulating cAMP/PKA pathway: the possible mechanism for caffeine-induced osteoporosis in women and estrogen's antagonistic effects.

Caffeine is consumed by most people in Europe and North America. As a risk factor for osteoporosis, caffeine has been reported to decrease bone mineral density, negatively influence calcium absorption and increase the risk of bone fracture in women. Except for the epidemiological observations and several studies which proved caffeine's unfavorable effects on osteoblast proliferation and impaired ability to form bone, little mechanism is known for the caffeine-induced osteoporosis. Since our unpublished studies showed that the precursor cells of osteoblasts, bone marrow-derived mesenchymal stem cells (BMSCs), were more sensitive than osteoblasts when exposed to the same dose of caffeine. We herein hypothesize that MSCs may be the primary target cells for caffeine-induced osteoporosis. It is well established that increasing cyclic 3',5'-adenosine monophosphate (cAMP) can regulate the expression of key genes involved in bone metabolism, including Cbfa1, PPARgamma, RANKL and OPG. We thereby propose the hypothesis that caffeine, a known inhibitor of cAMP phosphodiesterase, may affect bone metabolism by activating cAMP-dependent protein kinase A (PKA) pathway. In addition, considering the fact observed in epidemiology that caffeine's negative effects on bone only occurred in postmenopausal women and the inverse roles of caffeine and estrogen on bone metabolism, we postulate that caffeine may exert its undesirable influences on bone only in absence or low level of estrogen in vivo and estrogen may antagonize the adverse effect of caffeine on bone. Since several studies have demonstrated that estrogen may have ability to temper the biological effects of cAMP stimulators' roles on bone through cAMP to regulate some important genes' expression in bone metabolism. We assume that estrogen may block cAMP-dependent PKA pathway which is shared by caffeine, to exhibit its antagonistic roles.