Near-infrared light-triggered nitric oxide nanocomposites for photodynamic/photothermal complementary therapy against periodontal biofilm in an animal model.

Background: Periodontal disease, an oral disease that initiates with plaque biofilm infection, affects 10% of the global population. Due to the complexity of tooth root anatomy, biofilm resistance and antibiotic resistance, traditional mechanical debridement and antibiotic removal of biofilms are not ideal. Nitric oxide (NO) gas therapy and its multifunctional therapy are effective methods to clear biofilms. However, large and controlled delivery of NO gas molecules is currently a great challenge. Methods: The core-shell structure of Ag2S@ZIF-90/Arg/ICG was developed and characterized in detail. The ability of Ag2S@ZIF-90/Arg/ICG to produce heat, ROS and NO under 808 nm NIR excitation was detected by an infrared thermal camera, probes and Griess assay. In vitro anti-biofilm effects were evaluated by CFU, Dead/Live staining and MTT assays. Hematoxylin-eosin staining, Masson staining and immunofluorescence staining were used to analyze the therapeutic effects in vivo. Results: Antibacterial photothermal therapy (aPTT) and antibacterial photodynamic therapy (aPDT) could be excited by 808 nm NIR light, and the produced heat and ROS further triggered the release of NO gas molecules simultaneously. The antibiofilm effect had a 4-log reduction in vitro. The produced NO caused biofilm dispersion through the degradation of the c-di-AMP pathway and improved biofilm eradication performance. In addition, Ag2S@ZIF-90/Arg/ICG had the best therapeutic effect on periodontitis and NIR II imaging ability in vivo. Conclusions: We successfully prepared a novel nanocomposite with NO synergistic aPTT and aPDT. It had an outstanding therapeutic effect in treating deep tissue biofilm infection. This study not only enriches the research on compound therapy with NO gas therapy but also provides a new solution for other biofilm infection diseases.

Phototherapy improves cognitive function in dementia: A systematic review and meta-analysis.

This study aimed to investigate the effectiveness of phototherapy intervention on cognitive function in older adult patients with dementia. PubMed, Ovid MEDLINE, Web of Science, EMBASE, Cochrane Central Registry of Controlled Trials, PsycINFO, and Clinical Trials were searched from their inception to August 10, 2022, for randomized controlled trials involving patients with dementia who received phototherapy interventions. We used the weighted mean difference (MD) or standard weighted mean difference to generate the pooled estimates. The primary outcome was cognitive function as measured by the Mini-Mental State Examination (MMSE) score. The secondary outcomes were the behavioral and psychological symptoms of dementia (BPSDs) and sleep. This systematic review and meta-analysis was registered in PROSPERO (registration number: CRD42022343788). We included 12 randomized controlled trials comprising 766 patients with dementia (426 patients in the intervention group and 340 in the control group). Phototherapy interventions significantly improved MMSE scores (n = 3, MD 2.68, 95% confidence interval [CI]: 1.38-3.98, I2  = 0%). There were no significant differences in the Cornell Scale for Depression in Dementia score, Cohen-Mansfield Agitation Inventory score (MD: -3.12, 95% CI: -8.05, 1.82, I2  = 0%), Neuropsychiatric Inventory score, sleep efficiency, total sleep time, and Sleep Disorders Inventory score between the groups. Our systematic review and meta-analysis showed that phototherapy significantly improved cognitive function in patients with dementia.

A paraventricular thalamus to central amygdala neural circuit modulates acute stress-induced heightened wakefulness.

Heightened wakefulness in response to stressors is essential for survival but can also lead to sleep disorders like insomnia. The paraventricular thalamus (PVT) is both a critical thalamic area for wakefulness and a stress-sensitive brain region. However, whether the PVT and its neural circuitries are involved in controlling wakefulness in stress conditions remains unknown. Here, we find that PVT neurons projecting to the central amygdala (CeA) are activated by different stressors. These neurons are wakefulness-active and increase their activities upon sleep to wakefulness transitions. Optogenetic activation of the PVT-CeA circuit evokes transitions from sleep to wakefulness, whereas selectively silencing the activity of this circuit decreases time spent in wakefulness. Specifically, chemogenetic inhibition of CeA-projecting PVT neurons not only alleviates stress responses but also attenuates the acute stress-induced increase of wakefulness. Thus, our results demonstrate that the PVT-CeA circuit controls physiological wakefulness and modulates acute stress-induced heightened wakefulness.

The effectiveness of acupoint herbal patching for functional dyspepsia: A protocol for systematic review and meta-analysis.

BACKGROUND: Functional dyspepsia (FD) has gradually developed into a multiple disease of the digestive system that most patients may be accompanied by mental and emotional disorders, such as insomnia, anxiety, and depression. Acupoint herbal patching (AHP) is usually used as an alternative therapy for patients with FD. This study aimed to design a systematic review and meta-analysis to explore the effects of AHP on FD. METHODS: We will search the Cochrane Central Register of Controlled Trials, the Web of Science, PubMed, Embase, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, the Wan-Fang Database, and the China National Knowledge Infrastructure for randomized controlled trials of FD treated by AHP from inception to June 30, 2021. The primary outcome measures contain clinical effective rate, the symptom score of FD, and secondary outcome measures consist of quality of life, incidence of adverse events, and recurrence rate. We will use RevMan V.5.3 software to analyze data. Two reviewers will evaluate the risk of bias and the quality of the studies by the Cochrane Collaboration risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation approach, separately. RESULTS: This systematic review protocol will analyze the effectiveness, quality of life, improvement of the symptom, and safety of AHP therapy for FD. CONCLUSION: The findings of this systematic review will provide evidence to evaluate the effectiveness and safety of AHP for FD.

Efficacy and safety of electroacupuncture treatment in the prevention of negative moods in healthy young men after 30 h of total sleep deprivation: study protocol for a single-center, single-blind, parallel-arm, randomized clinical trial.

BACKGROUND: Sleep deprivation (SD) among young adults is a major public health concern. In humans, it has adverse effects on mood and results in serious health problems. Faced with SD, persons may take precautionary measures to try and reduce their risk. The aim of this study is to evaluate the efficacy and safety of electroacupuncture (EA) for the prevention of negative moods after SD. In addition, we will do a comparison of the effects of EA on mood after SD at different time points. METHODS: This randomized controlled trial (RCT) will be performed at the First Affiliated Hospital of Changchun University of Chinese Medicine in China. The Standards for Reporting Interventions in Clinical Trials of Acupuncture 2010 will be strictly adhered to. Forty-two healthy male volunteers will be distributed into acupoints electroacupuncture (AE) group, non-acupoints electroacupuncture (NAE) control group, or blank control group. This trial will comprise 1-week baseline (baseline sleep), 1-week preventative treatment, 30-h total sleep deprivation (TSD), and 24-h after waking follow-up period. Participants in the AE group and the NAE control group during the preventative treatment period will be administered with EA treatment once daily for 1 week. Participants in the blank control group will not be administered with any treatment. The primary outcome will be the Profile of Mood States (POMS) Scale. Secondary outcome measures will include changes in the Noldus FaceReader (a tool for automatic analysis of facial expressions) and Positive and Negative Affect Schedule (PANAS) Scale. Total sleep deprivation will be 30 h. During the 30-h TSD period, participants will be subjected to 11 sessions of assessment. Adverse events will be recorded. DISCUSSION: This study is designed to evaluate the efficacy and safety of EA for the prevention of negative moods after SD. The results of this trial will allow us to compare the effects of EA on mood after SD at different time points. Moreover, the findings from this trial will be published in peer-reviewed journals. TRIAL REGISTRATION: Chinese Clinical Trial Registry Chi2000039713 . Registered on 06 November 2020.

The effectiveness of acupoint application of traditional Chinese medicine in treating primary dysmenorrhea: A protocol for meta-analysis and data mining.

BACKGROUND: Primary dysmenorrhea (PD) is a functional disease of the female reproductive system, which has adverse effects on patients' physical and mental health and quality of life. At present, acupoint application of traditional Chinese medicine (TCM) as adjuvant therapy is undergoing clinical trials in different medical centers. However, there is no systematic review or meta-analysis to evaluate the efficacy of acupoint application of TCM in the treatment of PD. There is also a lack of systematic evaluation and analysis of acupoints and herbs. METHODS: All randomized controlled trials related to acupoint catgut embedding therapy on PD will be searched in the following electronic databases: Cochrane Central Registry of controlled trials, PubMed, Wed of Science, EMBASE, Science Net, China Biomedical Literature Database, China Science Journal Database, China National Knowledge Infrastructure and Wan-Fang Database, from inception to May, 2021 were searched without language restrictions. The primary outcomes contain visual analog score, The Cox Menstrual Symptom Scale, while the secondary outcomes consist of adverse events and the recurrence rate. Two reviewers will independently perform data selection, data synthesis, and quality assessment. Data meeting the inclusion criteria will be extracted and analyzed by Revman v.5.3 software. Two reviewers will evaluate the study using the Cochrane collaborative bias risk tool. We will use the scoring method to assess the overall quality of the evidence supporting the main results. We will also use Spass software (version 19.0) for complex network analysis to explore the potential core prescription of acupoint application of traditional Chinese medicine in the treatment of PD. RESULTS: This study will analyze the clinical effective rate, functional outcomes, quality of life, improvement of clinical symptoms of PD, and effective prescriptions of acupoint application for patients with PD. CONCLUSION: Our findings will provide evidence for the effectiveness and potential treatment prescriptions of acupoint application for patients with PD.PROSPERO registration number: CRD 42021244357.

The effectiveness of acupoint herbal patching for functional constipation: Protocol for a meta-analysis and data mining.

BACKGROUND: Functional constipation is a common functional problem of the digestive system that has a negative impact on physical, mental health of patients and quality of life. At present, acupoint herbal patching as an adjuvant therapy is currently undergoing clinical trials in different medical centers. However, no relevant systematic review or meta-analysis has been designed to evaluate the effects of acupoint herbal patching on functional constipation. There is also a lack of systematic evaluation and analysis of acupoints and herbs. METHODS: We will search the following 8 databases from their inception to November 15, 2020, without language restrictions: the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, the Wan-Fang Database and the China National Knowledge Infrastructure. The primary outcome measures will be clinical effective rate, functional outcomes, and quality of life. Data that meets the inclusion criteria will be extracted and analyzed using RevMan V.5.3 software. Two reviewers will evaluate the studies using the Cochrane Collaboration risk of bias tool. We will use the GRADE approach to assess the overall quality of evidence supporting the primary outcomes. We will also use Spass software (Version19.0) for complex network analysis to explore the potential core prescription of acupoint herbal patching for functional constipation. RESULTS: This study will analyze the clinical effective rate, functional outcomes, quality of life, improvement of clinical symptoms of functional constipation, and effective prescriptions of acupoint herbal patching for patients with functional constipation. CONCLUSION: Our findings will provide evidence for the effectiveness and potential treatment prescriptions of acupoint herbal patching for patients with functional constipation. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 42020193489.

Screening and isolation of potential neuraminidase inhibitors from leaves of Ligustrum lucidum Ait. based on ultrafiltration, LC/MS, and online extraction-separation methods.

Ultrafiltration liquid chromatography-mass spectrometry (ultrafiltration LC/MS) is introduced as an efficient method that can be applied to rapidly screen and identify ligands from the leaves of Ligustrum lucidum Ait. Using this method, we identified 13 compounds, including organic acids, flavonoids, and glycosides, as potent neuraminidase inhibitors. A continuous online method, employing pressurized liquid extraction followed by parallel centrifugal partition chromatography and preparative liquid chromatography PLE-(parallel-CPC/PLC), was developed for the efficient, scaled-up production of 12 compounds with high purities. The bioactivities of the separated compounds were assessed by an in vitro enzyme inhibition assay. The use of ultrafiltration LC/MS combined with PLE-(parallel-CPC/PLC), and an in vitro enzyme inhibition assay facilitated the efficient screening and isolation of neuraminidase inhibitors from complex samples, and could serve as an important platform for the large-scale production of functional ingredients.

In vitro screening and isolation of human aromatase inhibitors from Cicer arietinum by a novel continuous online method combining chromatographic techniques.

Ultrafiltration liquid chromatography with mass spectrometry can efficiently and rapidly screen and identify ligands from the seeds of Cicer arietinum for human aromatase. Using this method, we identified 11 major compounds, including organic acids, organic acid glycosides, flavone glycosides, isoflavones, and isoflavone glycosides, as potent human aromatase inhibitors. A continuous online method, including pressurized liquid extraction, countercurrent chromatography, and preparative liquid chromatography, was developed for scaling up the production of these compounds with high purity and efficiency. The bioactivity of the separated compounds was assessed by an in vitro enzyme inhibition assay. This novel approach using a combination of ultrafiltration liquid chromatography with mass spectrometry and pressurized liquid extraction with countercurrent chromatography and preparative liquid chromatography as well as an in vitro enzyme inhibition assay could be applied to efficiently screen and isolate human aromatase inhibitors from complex samples and to the large-scale production of functional food and nutraceutical ingredients.

Extraction and in vitro screening of potential acetylcholinesterase inhibitors from the leaves of Panax japonicus.

Ultrafiltration liquid chromatography-mass spectrometry (UFLC-MS) is an efficient method that can be applied to rapidly screen and identify ligands for acetylcholinesterase (AChE) from the leaves of Panax japonicus. Using this method, we identified 5 major compounds, chikusetsusaponins V, Ib, IV, IVa, and IVa ethyl ester, as potent AChE inhibitors, which were assessed for anti-Alzheimer disease activity using the PC12 cell model. A continuous online method, which consisted of microwave-assisted extraction, a solvent concentration tank, and centrifugal partition chromatography (MAE-SCT-CPC), was newly developed for scaled up production of these compounds with high purity and efficiency. The bioactivities of the compounds separated were assessed by the PC12 cell model. This novel approach of using UFLC-MS coupled with MAE-SCT-CPC and a PC12 cell model could be applied to efficiently screen, extract, and separate AChE inhibitors from complex samples, and could serve as an important platform for the large-scale production of functional food and nutraceutical ingredients.

Extraction and isolation of potential anti-stroke compounds from flowers of Pueraria lobata guided by in vitro PC12 cell model.

A simple and efficient method based on ultrafiltration liquid chromatography-mass spectrometry (UFLC-MS) was applied to rapidly screen and identify ligands for lactate dehydrogenase (LDH) from the flowers of Pueraria lobata, and the compounds were assessed for anti-stroke activity using a PC12 cell model. Seven major isoflavones, kakkalide, 3'-hydroxy puerarin, puerarin, puerarin xyloside, tectoridin, tectorigenin, and ononin, were identified as potent LDH inhibitors. A continuous online method, which consisted of microwave-assisted extraction and countercurrent chromatography (MAE-CCC), was newly developed for scaled-up production of these compounds with high purity and efficiency. This novel approach, using UFLC-MS coupled with MAE-CCC and a PC12 cell model, provided a powerful tool for screening, extraction, and separation of LDH inhibitors from complex samples, and a useful platform for the large-scale production of functional food and nutraceutical ingredients.

[Professor WANG Fuchun's experience in the acupoint selection of clinical treatment with acupuncture and moxibustion].

Professor WANG Fuchun's experience in the acupoint selection of clinical treatment with acupuncture and moxibustion was summarized. The main acupoints are selected by focusing on the chief symptoms of disease, the supplementary points are selected by differentiating the disorders. The acupoints are modified in terms of the changes of sickness. The effective acupoints are selected flexibly in accordance with the specific effects of points. The summary on the acupoint selection reflects professor WANG Fuchun's academic thoughts and clinical experience and effectively instructs the clinical practice of acupuncture and moxibustion.

Creation of Apolipoprotein C-II (ApoC-II) Mutant Mice and Correction of Their Hypertriglyceridemia with an ApoC-II Mimetic Peptide.

Apolipoprotein C-II (apoC-II) is a cofactor for lipoprotein lipase, a plasma enzyme that hydrolyzes triglycerides (TGs). ApoC-II deficiency in humans results in hypertriglyceridemia. We used zinc finger nucleases to create Apoc2 mutant mice to investigate the use of C-II-a, a short apoC-II mimetic peptide, as a therapy for apoC-II deficiency. Mutant mice produced a form of apoC-II with an uncleaved signal peptide that preferentially binds high-density lipoproteins (HDLs) due to a 3-amino acid deletion at the signal peptide cleavage site. Homozygous Apoc2 mutant mice had increased plasma TG (757.5 ± 281.2 mg/dl) and low HDL cholesterol (31.4 ± 14.7 mg/dl) compared with wild-type mice (TG, 55.9 ± 13.3 mg/dl; HDL cholesterol, 55.9 ± 14.3 mg/dl). TGs were found in light (density < 1.063 g/ml) lipoproteins in the size range of very-low-density lipoprotein and chylomicron remnants (40-200 nm). Intravenous injection of C-II-a (0.2, 1, and 5 µmol/kg) reduced plasma TG in a dose-dependent manner, with a maximum decrease of 90% occurring 30 minutes after the high dose. Plasma TG did not return to baseline until 48 hours later. Similar results were found with subcutaneous or intramuscular injections. Plasma half-life of C-II-a is 1.33 ± 0.72 hours, indicating that C-II-a only acutely activates lipolysis, and the sustained TG reduction is due to the relatively slow rate of new TG-rich lipoprotein synthesis. In summary, we describe a novel mouse model of apoC-II deficiency and show that an apoC-II mimetic peptide can reverse the hypertriglyceridemia in these mice, and thus could be a potential new therapy for apoC-II deficiency.