[Regulation of electroacupuncture on non-canonical pathway of hepatocellular pyroptosis in rats with nonalcoholic fatty liver disease].

OBJECTIVE: To observe the effect and mechanism of electroacupuncture (EA) on non-canonical pathway of hepatocellular pyroptosis in nonalcoholic fatty liver disease (NAFLD). METHODS: Sixty male SD rats were randomly divided into a normal diet group (n=15) and a high fat modeling group (n=45). The rats in the high fat modeling group were fed with customized high fat diet for 8 weeks to establish NAFLD model. Thirty successfully modeled rats were selected and randomly divided into a model group (n=10), an EA group (n=10) and a non-acupoint with shallow needling group (n=10), and 10 rats were randomly selected from the normal diet group as the control group additionally. In the EA group, EA was applied at bilateral "Fenglong" (ST 40) and "Ganshu" (BL 18), with disperse-dense wave, in frequency of 4 Hz/20 Hz and in intensity of 3 mA. In the non-acupoint with shallow needling group, shallow needling was delivered at points 5 mm from bilateral "Fenglong" (ST 40) and "Ganshu" (BL 18), the EA stimulation parameters were same as the EA group. The intervention was given once a day, 20 min a time, 5 days a week for 4 weeks in the two groups. After intervention, the liver morphology was observed by oil red "O" staining, the serum levels of lipopolysaccharide (LPS), interleukin (IL)-1ß, IL-18 and tumor necrosis factor-α (TNF-α) were detected by ELISA, the protein expression of gasdermin D (GSDMD), GSDMD-N, cysteine aspartic acid specific protease-11 (Caspase-11), IL-1ß, IL-18 and TNF-α in liver tissue were detected by Western blot, the mRNA expression of GSDMD, Caspase-11, IL-1ß, IL-18 and TNF-α in liver tissue was detected by real-time PCR in rats of each group. RESULTS: In the model group, vacuoles in different size were found in the hepatocellular cytoplasm, and the fat droplets were in schistose accumulation. Compared with the model group, the hepatocellular fat droplets and the degree of hepatic steatosis were reduced in the EA group and the non-acupoint with shallow needling group. Compared with the control group, the serum levels of LPS, IL-1ß, IL-18 and TNF-α were increased (P<0.01), the protein and mRNA expression of GSDMD, Caspase-11, IL-1ß, IL-18, TNF-α as well as the protein expression of GSDMD-N in the liver tissue were increased (P<0.01) in the model group. Compared with the model group, the serum levels of LPS, IL-1ß, IL-18 and TNF-α were decreased (P<0.01), the protein and mRNA expression of GSDMD, IL-1ß, IL-18 and TNF-α in the liver tissue were decreased (P<0.01), the protein expression of GSDMD-N and the mRNA expression of Caspase-11 in the liver tissue were decreased (P<0.01) in the EA group and the non-acupoint with shallow needling group. Compared with the model group, the protein expression of Caspase-11 in the liver tissue was decreased (P<0.01) in the EA group. Compared with the non-acupoint with shallow needling group, the serum levels of LPS, IL-1ß, IL-18 and TNF-α were decreased (P<0.01), the protein and mRNA expression of GSDMD, Caspase-11, IL-1ß and IL-18 in the liver tissue were decreased (P<0.01), the protein expression of GSDMD-N and the mRNA expression of TNF-α in the liver tissue were decreased (P<0.01) in the EA group. CONCLUSION: EA can inhibit hepatocellular pyroptosis in NAFLD rats, and its mechanism may be related to reducing the serum level of LPS, and down-regulating the expression of the non-canonical pathway related factors i.e. GSDMD, GSDMD-N, Caspase-11, IL-1ß, IL-18 and TNF-α.

Dendrobium officinale Polysaccharide (DOP) inhibits cell hyperproliferation, inflammation and oxidative stress to improve keratinocyte psoriasis-like state.

PURPOSE: Psoriasis is a skin disease characterized by excessive proliferation, inflammation and oxidative stress in keratinocytes. The present study aimed to investigate the therapeutic effects of Dendrobium officinale polysaccharide (DOP) on keratinocyte psoriasis-like models. METHODS: The HaCaT keratinocyte inflammation models were induced by interleukin (IL)-22 or lipopolysaccharide (LPS), respectively, and oxidative stress damage within cells was elicited by H2O2 and treated using DOP. CCK-8 and EdU were carried out to detect cell proliferation. ELISA, qRT-PCR, and Western blot were conducted to measure the expression of pro-inflammatory cytokines IL17A, IL-23, IL1ß, tumor necrosis factor alpha (TNF-α), and IL-6. Reactive oxygen species (ROS) level in keratinocytes was detected by flow cytometry. Cell proliferation-associated proteins (PCNA, Ki67, Cyclin D1) and pathway proteins (p-AKT and AKT), and oxidative stress marker proteins (Nrf-2, CAT, SOD1) were detected by Western blot. RESULT: DOP did not affect the proliferation of normal keratinocytes, but DOP was able to inhibit the proliferative activity of IL-22-induced overproliferating keratinocytes and suppress the expression of proliferation-related factors PCNA, Ki67, and Cyclin D1 as well as the proliferation pathway p-AKT. In addition, DOP treatment was able to inhibit IL-22 and LPS-induced inflammation and H2O2-induced oxidative stress, including the expression of IL17A, IL-23, IL1ß, TNF-α, IL-6, and IL1ß, as well as the expression levels of intracellular ROS levels and cellular oxidative stress-related indicators SOD, MDA, CAT, Nrf-2 and SOD1. CONCLUSION: DOP inhibits keratinocyte hyperproliferation, inflammation and oxidative stress to improve the keratinocyte psoriasis-like state.

Surgical performance of dental students using computer-assisted dynamic navigation and freehand approaches.

INTRODUCTION: Nowadays, the training of implant placement has shifted from once entirely instructor-student teaching to the increasing use of computer-assisted simulation. Based on computerized virtual planning, dynamic navigation has been used for implant placement with higher accuracy than the traditional freehand protocol. However, whether dynamic navigation benefits to the training of dental students in implant placement remains controversial. This study aimed to compare the surgical performance of dental students in implant placement using computer-assisted dynamic navigation and freehand approaches. MATERIALS AND METHODS: A total of 20 dental students (6 males, 14 females, age: 25.6 ± 0.5 years) were enrolled in this study. With the traditional freehand approach (training 1) as the control protocol, computer-assisted dynamic navigation (training 2) was used in the training of dental students in implant placement. For each training, both the operating time (OT) of students and placement accuracy represented by the linear (at the implant platform, Dpl, and apex, Dap) and angular (Dan) deviations between the virtually planned and placed implants were recorded. Statistical comparisons were made between the two training protocols as well as male and female surgeons. RESULTS: OT2 was around twice of OT1 (p < .0001), whereas Dan1 was almost three times of Dan2 (p < .0001). Dap1 and Dpl1 were significantly higher than Dap2 (p = .014) and Dpl2 (p = .033) respectively. Besides, male students showed statistically higher Dpl1 (p = .033) and Dan1 (p = .002) than females. No significant difference was found between male and female students in OT1, OT2, Dpl2, Dap1, Dap2 and Dan2. CONCLUSIONS: Within the limitations of this study, the use of computer-assisted dynamic navigation in the preclinical training could improve the surgical performance of the dental students in implant placement. The combination of dynamic navigation with the traditional preclinical surgical training may benefit to dental students and could be applied in dental education.

Cracking the code: Deciphering the role of the tumor microenvironment in osteosarcoma metastasis.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. It is characterized by a rapid progression, poor prognosis, and early pulmonary metastasis. Over the past 30 years, approximately 85% of patients with osteosarcoma have experienced metastasis. The five-year survival of patients with lung metastasis during the early stages of treatment is less than 20%. The tumor microenvironment (TME) not only provides conditions for tumor cell growth but also releases a variety of substances that can promote the metastasis of tumor cells to other tissues and organs. Currently, there is limited research on the role of the TME in osteosarcoma metastasis. Therefore, to explore methods for regulating osteosarcoma metastasis, further investigations must be conducted from the perspective of the TME. This will help to identify new potential biomarkers for predicting osteosarcoma metastasis and assist in the discovery of new drugs that target regulatory mechanisms for clinical diagnosis and treatment. This paper reviews the research progress on the mechanism of osteosarcoma metastasis based on TME theory, which will provide guidance for the clinical treatment of osteosarcoma.

Optimized osteogenesis of biological hydroxyapatite-based bone grafting materials by ion doping and osteoimmunomodulation.

BACKGROUND: Biological hydroxyapatite (BHA)-based bone grafting materials have been widely used for bone regeneration in implant surgery. Much effort has been made in the improvement of their osteogenic property as it remains unsatisfactory for clinical use. Osteoimmunomodulation plays a significant role in bone regeneration, which is highly related to active inorganic ions. Therefore, attempts have been made to obtain osteoimmunomodulatory BHA-based bone grafting materials with optimized osteogenic property by ion doping. OBJECTIVE: To summarize and discuss the active inorganic ions doped into BHA and their effects on BHA-based bone grafting materials. METHOD: A literature search was performed in databases including Google Scholar, Web of Science and PubMed, with the elementary keywords of "ion doped" and "biological hydroxyapatite", as well as several supplementary keywords. All document types were included in this search. The searching period and language were not limited and kept updated to 2022. RESULTS: A total of 32 articles were finally included, of which 32 discussed the physiochemical properties of BHA-based biomaterials, while 12 investigated their biological features in vitro, and only three examined their biological performance in vivo. Various ions were doped into BHA, including fluoride, zinc, magnesium and lithium. Such ions improved the biological performance of BHA-based biomaterials, which was attributed to their osteoimmunomodulatory effect. CONCLUSION: The doping of active inorganic ions is a reliable strategy to endow BHA-based biomaterials with osteoimmunomodulatory property and promote bone regeneration. Further studies are still in need to explore more ions and their effects in the crosstalk between the skeletal and immune systems.

Brevicidine acts as an effective sensitizer of outer membrane-impermeable conventional antibiotics for Acinetobacter baumannii treatment.

The antibiotic resistance of Acinetobacter baumannii poses a significant threat to global public health, especially those strains that are resistant to carbapenems. Therefore, novel strategies are desperately needed for the treatment of infections caused by antibiotic-resistant A. baumannii. In this study, we report that brevicidine, a bacterial non-ribosomally produced cyclic lipopeptide, shows synergistic effects with multiple outer membrane-impermeable conventional antibiotics against A. baumannii. In particular, brevicidine, at a concentration of 1 µM, lowered the minimum inhibitory concentration of erythromycin, azithromycin, and rifampicin against A. baumannii strains by 32-128-fold. Furthermore, mechanistic studies were performed by employing erythromycin as an example of an outer membrane-impermeable conventional antibiotic, which showed the best synergistic effects with brevicidine against the tested A. baumannii strains in the present study. The results demonstrate that brevicidine disrupted the outer membrane of A. baumannii at a concentration range of 0.125-4 µM in a dose-dependent manner. This capacity of brevicidine could help the tested outer membrane-impermeable antibiotics enter A. baumannii cells and thereafter exert their antimicrobial activity. In addition, the results show that brevicidine-erythromycin combination exerted strong A. baumannii killing capacity by the enhanced inhibition of adenosine triphosphate biosynthesis and accumulation of reactive oxygen species, which are the main mechanisms causing the death of bacteria. Interestingly, brevicidine and erythromycin combination showed good therapeutic effects on A. baumannii-induced mouse peritonitis-sepsis models. These findings demonstrate that brevicidine is a promising sensitizer candidate of outer membrane-impermeable conventional antibiotics for treating A. baumannii infections in the post-antibiotic age.

Chemical peeling with 35% glycolic acid for the treatment of disseminated facial verruca plana: A randomized, split-face, evaluator-blinded trial.

Disseminated facial verruca plana is a chronic disorder that causes significant psychological distress. However, safe and effective treatment is lacking. This study aimed to explore the efficacy and safety of 35% glycolic acid (GA) for the treatment of disseminated facial verruca plana. A split-face clinical trial was conducted to explore the efficacy and safety of using chemical peeling with 35% GA for the treatment of disseminated facial verruca plana. One side of the face was applied with 35% GA once every fortnight for a total of three times. Adapalene gel was applied every night to the other side of the face as the control. The clearance rate of lesions was evaluated at different time points. Between June 2020 and December 2020, 30 patients with disseminated verruca plana who visited the Dermatology Hospital of Southern Medical University were enrolled. After three chemical peelings with 35% GA that was applied at 2-week intervals, 15 (50%) patients achieved >70% lesion reduction. The same effective rate in the adapalene gel-treated side of the face was documented in eight patients. Subgroup analysis showed a higher clearance rate in patients with a shorter disease duration. Moreover, concurrent improvements in facial roughness were observed in the 35% GA-treated group. Adverse effects including mild erythema and desquamation were observed during chemical peeling with 35% GA. In conclusion, chemical peeling with 35% GA could be a safe and effective option for treating disseminated facial verruca plana, especially for those who desire skin improvement.

One half-scan dual-energy CT imaging using the Dual-domain Dual-way Estimated Network (DoDa-Net) model.

BACKGROUND: Compared with single-energy computed tomography (CT), dual-energy CT (DECT) can distinguish materials better. However, most DECT reconstruction theories require two full-scan projection datasets of different energies, and this requirement is hard to meet, especially for cases where a physical blockage disables a full circular rotation. Thus, it is critical to relax the requirements of data acquisition to promote the application of DECT. METHODS: A flexible one half-scan DECT scheme is proposed, which acquires two projection datasets on two-quarter arcs (one for each energy). The limited-angle problem of the one half-scan DECT scheme can be solved by a reconstruction method. Thus, a dual-domain dual-way estimation network called DoDa-Net is proposed by utilizing the ability of deep learning in non-linear mapping. Specifically, the dual-way mapping Generative Adversarial Network (DM-GAN) was first designed to mine the relationship between two different energy projection data. Two half-scan projection datasets were obtained, the data of which was twice that of the original projection dataset. Furthermore, the data transformation from the projection domain to the image domain was realized by the total variation (TV)-based method. In addition, the image processing network (Im-Net) was employed to optimize the image domain data. RESULTS: The proposed method was applied to a digital phantom and real anthropomorphic head phantom data to verify its effectiveness. The reconstruction results of the real data are encouraging and prove the proposed method's ability to suppress noise while preserving image details. Also, the experiments conducted on simulated data show that the proposed method obtains the closest results to the ground truth among the comparison methods. For low- and high-energy reconstruction, the peak signal-to-noise ratio (PSNR) of the proposed method is as high as 40.3899 and 40.5573 dB, while the PSNR of other methods is lower than 36.5200 dB. Compared with FBP, TV, and other GAN-based methods, the proposed method reduces root mean square error (RMSE) by, respectively, 0.0124, 0.0037, and 0.0016 for low-energy reconstruction, and 0.0102, 0.0028, and 0.0015 for high-energy reconstruction. CONCLUSIONS: The developed DoDa-Net model for the proposed one half-scan DECT scheme consists of two stages. In stage one, DM-GAN is used to realize the dual map of projection data. In stage two, the TV-based method is employed to transform the data from the projection domain to the image domain. Furthermore, the reconstructed image is processed by the Im-Net. According to the experimental results of qualitative and quantitative evaluation, the proposed method has advantages in detail preservation, indicating the potential of the proposed method in one half-scan DECT reconstruction.

Manipulation of cadmium and diethylhexyl phthalate on Rana chensinensis tadpoles affects the intestinal microbiota and fatty acid metabolism.

Gastrointestinal tract and intestine microbiota can both have deep effects on the lipid metabolism and immune function of amphibians. Additionally, the composition and structure of the microbial community are influenced by environmental pollutions. It is noteworthy that environmental compounds such as Cd and DEHP are pervasive in the aquatic environment and do not exist in isolation, and single exposure experiments cannot well explain the effects of unpredictable interactions between co-existing compounds on amphibians. In this study, we calculated the parameters of morphological and histological indices of Rana chensinensis tadpoles after treated with Cd and/or DEHP. The 16S rRNA gene sequencing technology was used to assess the relative abundance of intestinal microbial community among tadpoles from each treatment groups. We also examined the mRNA expression levels of lipid digestion and absorption and SCFAs related-genes. Our results indicated that all morphological and histological indices were significantly declined in the Cd treatment group, while the mixed treatment group was similar to the control group. Compared with the control group, the relative abundances of Firmicutes, Proteobacteria and Verrucomicrobia exhibited distinctive differences in Cd and/or DEHP treatment groups. Further, RT-qPCR results revealed that the expression levels of lipid metabolism and SCFAs related-genes were also significantly altered among the treatment groups. Taken together, the present study highlighted a new evidence that the alterations in intestinal microbial community and mRNA expression levels of larval amphibians after exposure to Cd and/or DEHP may impair lipid storage and transport, as well as reduce anti-inflammatory capacity, which may ultimately lead to a decline in amphibian populations.