The global patent landscape of emerging infectious disease monkeypox.

BACKGROUND: Monkeypox is an emerging infectious disease with confirmed cases and deaths in several parts of the world. In light of this crisis, this study aims to analyze the global knowledge pattern of monkeypox-related patents and explore current trends and future technical directions in the medical development of monkeypox to inform research and policy. METHODS: A comprehensive study of 1,791 monkeypox-related patents worldwide was conducted using the Derwent patent database by descriptive statistics, social network method and linear regression analysis. RESULTS: Since the 21st century, the number of monkeypox-related patents has increased rapidly, accompanied by increases in collaboration between commercial and academic patentees. Enterprises contributed the most in patent quantity, whereas the initial milestone patent was filed by academia. The core developments of technology related to the monkeypox include biological and chemical medicine. The innovations of vaccines and virus testing lack sufficient patent support in portfolios. CONCLUSIONS: Monkeypox-related therapeutic innovation is geographically limited with strong international intellectual property right barriers though it has increased rapidly in recent years. The transparent licensing of patent knowledge is driven by the merger and acquisition model, and the venture capital, intellectual property and contract research organization model. Currently, the patent thicket phenomenon in the monkeypox field may slow the progress of efforts to combat monkeypox. Enterprises should pay more attention to the sharing of technical knowledge, make full use of drug repurposing strategies, and promote innovation of monkeypox-related technology in hotspots of antivirals (such as tecovirimat, cidofovir, brincidofovir), vaccines (JYNNEOS, ACAM2000), herbal medicine and gene therapy.

Electroacupuncture of the cymba concha alleviates p-chlorophenylalanine-induced insomnia in mice.

OBJECTIVE: Insomnia is the most common sleep disorder and is often comorbid with mental and physical diseases. The present study was designed to investigate the hypnotic effect of electroacupuncture (EA) of the cymba concha to stimulate the auricular branch of the vagus nerve (ABVN). METHODS: Mice were intraperitoneally injected with p-chlorophenylalanine (PCPA, 300 mg/kg·d) for 2 days to induce insomnia and subsequently received EA or manual acupuncture (MA) of the cymba concha for 30 min once daily for 5 consecutive days, or no treatment. The phenobarbital-induced sleep test was used to analyze the hypnotic effects and the open field test was used to analyze the locomotor activities and anxiolytic effects of EA/MA of the cymba concha. In addition, the levels of gamma-aminobutyric acid (GABA) and glutamate (Glu) in the hypothalamus and peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: PCPA injection significantly decreased sleep duration, increased sleep latency and induced anxiety-like behaviors in mice. In PCPA-insulted mice, EA of the cymba concha improved the sleep disturbance by significantly prolonging sleep duration, while no change in sleep latency was observed. Moreover, EA of the cymba concha improved PCPA-induced anxiety-like behaviors without decreasing locomotor activities in the open field test. EA of the cymba concha increased the level of GABA in the hypothalamus and peripheral blood, while Glu concentrations remained unchanged. CONCLUSION: These findings indicate that EA of the region innervated by the ABVN upregulates GABA levels in the hypothalamus and ameliorates the symptoms of insomnia and anxiety, suggesting that EA of the cymba concha might have potential value as an intervention for insomnia.

What, Where, When and How of COVID-19 Patents Landscape: A Bibliometrics Review.

Two years after COVID-19 came into being, many technologies have been developed to bring highly promising bedside methods to help fight this epidemic disease. However, owing to viral mutation, how far the promise can be realized remains unclear. Patents might act as an additional source of information for informing research and policy and anticipating important future technology developments. A comprehensive study of 3741 COVID-19-related patents (3,543 patent families) worldwide was conducted using the Derwent Innovation database. Descriptive statistics and social network analysis were used in the patent landscape. The number of COVID-19 applications, especially those related to treatment and prevention, continued to rise, accompanied by increases in governmental and academic patent assignees. Although China dominated COVID-19 technologies, this position is worth discussing, especially in terms of the outstanding role of India and the US in the assignee collaboration network as well as the outstanding invention portfolio in Italy. Intellectual property barriers and racist treatment were reduced, as reflected by individual partnerships, transparent commercial licensing and diversified portfolios. Critical technological issues are personalized immunity, traditional Chinese medicine, epidemic prediction, artificial intelligence tools, and nucleic acid detection. Notable challenges include balancing commercial competition and humanitarian interests. The results provide a significant reference for decision-making by researchers, clinicians, policymakers, and investors with an interest in COVID-19 control.

Characteristic flavor formation of thermally processed N-(1-deoxy-α-d-ribulos-1-yl)-glycine: Decisive role of additional amino acids and promotional effect of glyoxal.

The role of amino acids and α-dicarbonyls in the flavor formation of Amadori rearrangement product (ARP) during thermal processing was investigated. Comparisons of the volatile compounds and their concentrations when N-(1-deoxy-α-d-ribulos-1-yl)-glycine reacted with different amino acids or glyoxal (GO) at 100 °C were executed. Additional amino acids, such as glycine (Gly), in ARP models contributed to the diversity of furanoids by the chain elongation of the derived formaldehyde. Whereas the monoanion of additional glutamic acid acted as nucleophile, favored 2-ethyl-3,5-dimethylpyrazine and 2,5-dimethylpyrazine formation; the nonionized amino group of additional lysine were involved in α-dicarbonyls formation, causing pyrazine and methylpyrazine accumulation in the ARP model. Moreover, the high dosage and pH stabilization of additional GO probably promoted the ARP degradation and deoxyosones retro-aldol cleavage, resulting in methylpyrazine rather than furanoids formation. The present work provided the guidance for the controlled flavor formation of ARP in industrial application.

Oral supplementation of inorganic pyrophosphate in pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE; OMIM 264800) is a rare heritable multisystem disorder, characterized by ectopic mineralization affecting elastic fibres in the skin, eyes and the cardiovascular system. Skin findings often lead to early diagnosis of PXE, but currently, no specific treatment exists to counteract the progression of symptoms. PXE belongs to a group of Mendelian calcification disorders linked to pyrophosphate metabolism, which also includes generalized arterial calcification of infancy (GACI) and arterial calcification due to CD73 deficiency (ACDC). Inactivating mutations in ABCC6, ENPP1 and NT5E are the genetic cause of these diseases, respectively, and all of them result in reduced inorganic pyrophosphate (PPi ) concentration in the circulation. Although PPi is a strong inhibitor of ectopic calcification, oral supplementation therapy was initially not considered because of its low bioavailability. Our earlier work however demonstrated that orally administered pyrophosphate inhibits ectopic calcification in the animal models of PXE and GACI, and that orally given Na4 P2 O7 is absorbed in humans. Here, we report that gelatin-encapsulated Na2 H2 P2 O7  has similar absorption properties in healthy volunteers and people affected by PXE. The sodium-free K2 H2 P2 O7 form resulted in similar uptake in healthy volunteers and inhibited calcification in Abcc6-/- mice as effectively as its sodium counterpart. Novel pyrophosphate compounds showing higher bioavailability in mice were also identified. Our results provide an important step towards testing oral PPi in clinical trials in PXE, or potentially any condition accompanied by ectopic calcification including diabetes, chronic kidney disease or ageing.

Current neurologic treatment and emerging therapies in CDKL5 deficiency disorder.

BACKGROUND: CDKL5 deficiency disorder (CDD) is associated with refractory infantile onset epilepsy, global developmental delay, and variable features that include sleep, behavioral disturbances, and movement disorders. Current treatment is primarily symptom-based and informed by experience in caring for this population. METHODS: We describe medication and non-medication approaches to treatment of epilepsy and additional key neurologic symptoms (sleep disturbances, behavioral issues, movement disorders, and swallowing dysfunction) in a cohort of 177 individuals meeting criteria for CDD, 154 evaluated at 4 CDKL5 Centers of Excellence in the USA and 40 identified through the NIH Natural History Study of Rett and Related Disorders. RESULTS: The four most frequently prescribed anti-seizure medications were broad spectrum, prescribed in over 50% of individuals. While the goal was not to ascertain efficacy, we obtained data from 86 individuals regarding response to treatment, with 2-week response achieved in 14-48% and sustained 3-month response in 5-36%, of those with known response. Additional treatments for seizures included cannabis derivatives, tried in over one-third of individuals, and clinical trial medications. In combination with pharmacological treatment, 50% of individuals were treated with ketogenic diet for attempted seizure control. Surgical approaches included vagus nerve stimulators, functional hemispherectomy, and corpus callosotomy, but numbers were too limited to assess response. Nearly one-third of individuals received pharmacologic treatment for sleep disturbances, 13% for behavioral dysregulation and movement disorders, and 43% had gastrostomy tubes. CONCLUSIONS: Treatment for neurologic features of CDD is currently symptom-based and empiric rather than CDD-specific, though clinical trials for CDD are emerging. Epilepsy in this population is highly refractory, and no specific anti-seizure medication was associated with improved seizure control. Ketogenic diet is commonly used in patients with CDD. While behavioral interventions are commonly instituted, information on the use of medications for sleep, behavioral management, and movement disorders is sparse and would benefit from further characterization and optimization of treatment approaches. The heterogeneity in treatment approaches highlights the need for systematic review and guidelines for CDD. Additional disease-specific and disease-modifying treatments are in development.

Effects of Rumen-Protected Niacin on Dry Matter Intake, Milk Production, Apparent Total Tract Digestibility, and Faecal Bacterial Community in Multiparous Holstein Dairy Cow during the Postpartum Period.

Extensive studies about rumen-protected niacin (RPN) supplementation on dairy cows in early-lactation have been done, but the effects of RPN on changes in dry matter intake (DMI), milk production, feed digestibility, and fecal bacterial community were conflicting. The aim of this study was to investigate them affected by RPN in postpartum cows. Multiparous Holstein dairy cows (n = 12, parity = 3.5 ± 0.5, body weights = 740 ± 28 kg) were divided into two groups supplemented with either 0 (CON) or 20 g/d RPN (RPN). Our results showed that RPN supplementation increased DMI and milk production of cows during the first three weeks after calving (p < 0.05). The concentrations of neuropeptide Y and orexin A were significantly higher in RPN group than that in the CON group during postpartum period (p < 0.05). The apparent total-tract digestibility of nutrients was similar between the CON and RPN groups at 2 weeks after calving (p > 0.05). The 16S rRNA gene sequencing analysis showed that RPN had no impact on the alpha and beta diversity, although 4 genera were changed in cow feces at 14 days after calving. Overall, 20 g/d RPN added to the diet could improve DMI and milk yield up to two weeks after calving with little influence on feed digestibility.

High internal phase pickering emulsions stabilized by pea protein isolate-high methoxyl pectin-EGCG complex: Interfacial properties and microstructure.

The pea protein isolate-high methoxyl pectin-epigallocatechin gallate (PPI-HMP-EGCG) complex was used to stabilize Pickering emulsions (PEs) and high internal phase PEs (HIPPEs), and the effect of interfacial rheology on the microstructure, bulk rheology and stability of these emulsions was investigated. The PPI-HMP-EGCG complex with PPI to EGCG 30:1 exhibited partial wettability (81.6 ± 0.4°) and optimal viscoelasticity for the formation of stable interfacial layer. The microstructure demonstrated that the PPI-HMP-EGCG complex acted as an interfacial layer and surrounded the oil droplets, and continuous phases were mainly filled with excessive HMP, which enhanced emulsion stability. The formation of a firm gel-like network structure required a dense interfacial layer to provide the PEs (complex concentration of 0.1%) and HIPPEs (oil-phase up to 0.83) with ideal viscoelasticity and stability. The results provide the guidelines for the rational design of EGCG-loaded HIPPEs stabilized by water-soluble protein/polysaccharide complexes.

Deciphering of Key Pharmacological Pathways of Poria Cocos Intervention in Breast Cancer Based on Integrated Pharmacological Method.

OBJECTIVE: Poria cocos (Fuling), a natural plant, has recently emerged as a promising strategy for cancer treatment. However, the molecular mechanisms of Poria cocos action in breast cancer remain poorly understood. METHODS: TCMSP database was used to screen the potential active ingredients in Poria cocos. GEO database was used to identify differentially expressed genes. Network pharmacology was used to identify the specific pathways and key target proteins related to breast cancer. Finally, molecular docking was used to validate the results. RESULTS: In our study, 237 targets were predicted for 15 potential active ingredients found in Poria cocos. An interaction network of predicted targets and genes differentially regulated in breast cancers was constructed. Based on the constructed network and further analysis including network topology, KEGG, survival analysis, and gene set enrichment analysis, 3 primary nodes were identified as key potential targets that were significantly enriched in the PPAR signaling pathway. CONCLUSION: The results showed that potential active ingredients of Poria cocos might interfere with breast cancer through synergistic regulation of PTGS2, ESR1, and FOS.

Ancient genomes reveal tropical bovid species in the Tibetan Plateau contributed to the prevalence of hunting game until the late Neolithic.

Local wild bovids have been determined to be important prey on the northeastern Tibetan Plateau (NETP), where hunting game was a major subsistence strategy until the late Neolithic, when farming lifestyles dominated in the neighboring Loess Plateau. However, the species affiliation and population ecology of these prehistoric wild bovids in the prehistoric NETP remain unknown. Ancient DNA (aDNA) analysis is highly informative in decoding this puzzle. Here, we applied aDNA analysis to fragmented bovid and rhinoceros specimens dating ∼5,200 y B.P. from the Neolithic site of Shannashuzha located in the marginal area of the NETP. Utilizing both whole genomes and mitochondrial DNA, our results demonstrate that the range of the present-day tropical gaur (Bos gaurus) extended as far north as the margins of the NETP during the late Neolithic from ∼29°N to ∼34°N. Furthermore, comparative analysis with zooarchaeological and paleoclimatic evidence indicated that a high summer temperature in the late Neolithic might have facilitated the northward expansion of tropical animals (at least gaur and Sumatran-like rhinoceros) to the NETP. This enriched the diversity of wildlife, thus providing abundant hunting resources for humans and facilitating the exploration of the Tibetan Plateau as one of the last habitats for hunting game in East Asia.

Assessment of Hypokalemia and Clinical Characteristics in Patients With Coronavirus Disease 2019 in Wenzhou, China.

Importance: Severe acute respiratory syndrome coronavirus 2 has caused a global outbreak of coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 binds angiotensin-converting enzyme 2 of the rennin-angiotensin system, resulting in hypokalemia. Objective: To investigate the prevalence, causes, and clinical implications of hypokalemia, including its possible association with treatment outcomes, among patients with COVID-19. Design, Setting, and Participants: This cohort study was conducted at Wenzhou Central Hospital and Sixth People's Hospital of Wenzhou, Wenzhou, China, from January 11, 2020, to February 15, 2020. Participants included patients who received a diagnosis of COVID-19 according to the criteria issued by the Chinese Health Bureau and were admitted to the hospital. The patients were classified as having severe hypokalemia (plasma potassium <3 mmol/L), hypokalemia (plasma potassium 3-3.5 mmol/L), and normokalemia (plasma potassium >3.5 mmol/L). The clinical features, therapy, and outcomes were compared between the 3 groups. Data analysis was conducted in March 2020. Interventions: The patients were given general support and antiviral therapy. Their epidemiological and clinical features were collected. Main Outcomes and Measures: The prevalence of hypokalemia and response to treatment with potassium supplements were measured by analyzing plasma and urine potassium levels. Results: One hundred seventy-five patients (87 female patients [50%]; mean [SD] age, 45 [14] years) were classified as having severe hypokalemia (31 patients [18%]), hypokalemia (64 patients [37%]), and normokalemia (80 patients [46%]). Patients with severe hypokalemia had statistically significantly higher body temperature (mean [SD], 37.6 °C [0.9 °C]) than the patients with hypokalemia (mean [SD], 37.2 °C [0.7 °C]; difference, 0.4 °C; 95% CI, 0.2-0.6 °C; P = .02) and the patients with normokalemia (mean [SD], 37.1 °C [0.8 °C]; difference, 0.5 °C; 95% CI, 0.3-0.7 °C; P = .005). Patients with higher levels of hypokalemia also had higher creatine kinase levels (severe hypokalemia, mean [SD], 200 [257] U/L [median, 113 U/L; interquartile range {IQR}, 61-242 U/L]; hypokalemia, mean [SD], 97 [85] U/L; and normokalemia, mean [SD], 82 [57] U/L), higher creatine kinase-MB fraction (severe hypokalemia, mean [SD], 32 [39] U/L [median, 14 U/L; IQR, 11-36 U/L]; hypokalemia, mean [SD], 18 [15] U/L; and normokalemia, mean [SD], 15 [8] U/L), higher lactate dehydrogenase levels (mean [SD], severe hypokalemia, 256 [88] U/L; hypokalemia, 212 [59] U/L; and normokalemia, 199 [61] U/L), and higher C-reactive protein levels (severe hypokalemia, mean [SD], 29 [23] mg/L; hypokalemia, mean [SD], 18 [20] mg/L [median, 12, mg/L; IQR, 4-25 mg/L]; and normokalemia, mean [SD], 15 [18] mg/L [median, 6 U/L; IQR, 3-17 U/L]). Of 40 severely and critically ill patients, 34 (85%) had hypokalemia. Patients with severe hypokalemia were given potassium at a dose of 40 mEq per day, for a total mean (SD) of 453 (53) mEq potassium chloride, during the hospital stay. The patients responded well to potassium supplements as they recovered. Conclusions and Relevance: The correction of hypokalemia is challenging because of continuous renal potassium loss resulting from the degradation of angiotensin-converting enzyme 2. The high prevalence of hypokalemia among patients with COVID-19 suggests the presence of disordered rennin-angiotensin system activity, which increases as a result of reduced counteractivity of angiotensin-converting enzyme 2, which is bound by severe acute respiratory syndrome coronavirus 2.

Preparation of phytosteryl ornithine ester hydrochloride and improvement of its bioaccessibility and cholesterol-reducing activity in vitro.

In this work, synthesis of phytosteryl ornithine ester hydrochloride was studied for the first time using an intermediate phytosteryl N,N'-bis[tert-butoloxycarbonyl(BOC)]-ornithine ester. This method also involved esterification of phytosterols with N,N'-bis(BOC)-ornithine and deprotection. The maximum yield was 90% and deprotection of BOC group was more than 99% using the HCl/ethyl acetate method. As a result, thermal stability and water solubility as well as emulsifying activity and stability of phytosterols were improved through coupling with ornithine, which is favorable for their application in water-based food systems. We also observed increased bioaccessibility of phytosteryl ornithine hydrochloride (4.5%) and 65% of phytosteryl ornithine hydrochloride was hydrolyzed in vitro. These results indicated that ornithine phytosteryl ester hydrochloride can reduce dissolution capacity of cholesterol in vitro, representing improved cholesterol-reducing activity, which will further expand the applications of phytosteryl ornithine ester hydrochloride.

Enhancement of coffee brew aroma through control of the aroma staling pathway of 2-furfurylthiol.

During storage of coffee, the key aroma 2-furfurylthiol becomes less active, the mechanisms of this loss and ways to mitigate it were investigated. Aroma profiles were analyzed using GC-MS and sensory properties were evaluated by Quantitative Descriptive Analysis. Quinones, as the oxidation products of hydroxydroquinone, was found to actively bind 2-furfurylthiol, which accounted for the loss of 2-furfurylthiol. To mitigate this loss, ingredients were screened for their ability to prevent 2-furfurylthiol from loss. Cysteine had the highest 2-furfurylthiol releasing efficiency and ascorbic acid was also selected due to its 2-furfurylthiol releasing ability in Fenton reaction system. Concentrations were optimized and the addition of 0.045 g/L cysteine and 0.05 g/L ascorbic acid directly protected aroma during storage, these included 2-furfurylthiol, dimethyltrisulfide, methyl furfuryl disulfide, 4-ethylguaiacol and 4-vinylguaiacol. Ultimately, sensory testing showed a direct enhancement in nutty, sulfurous and roasted aroma attributes, an increase in flavour intensity and preference over shelf life.

Effects of sorafenib on fibroblast-like synoviocyte apoptosis in rats with adjuvant arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by synovial inflammation and hyperplasia resulting from an imbalance between the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs). Our previous study found that sorafenib had inhibitory effects in rats with adjuvant arthritis (AA). The present study investigated the role of sorafenib in the induction of AA FLS apoptosis in vitro. FLSs obtained from AA rats were cultured in vitro and identified. Cell apoptosis was detected using terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) labeling methods. Real-time PCR and Western blotting assays were used to quantify the expression levels of Fas, Caspase-3, Mcl-1, NF-κB and C-jun gene products in AA FLSs. Our data revealed that sorafenib (4 µmol/L) induced apoptosis in AA FLSs, and flow cytometry analysis showed that AA FLSs treated with sorafenib (4 µmol/L) in vitro accumulated in early and late apoptosis. There were significant increases in the expression levels of Fas, Caspase-3 and Mcl-1, and significant decreases in NF-κB and C-jun expression in AA FLSs treated with sorafenib. In summary, these results demonstrate that sorafenib promotes AA FLS apoptosis, which may be related to the upregulation of Fas and Caspase-3 and downregulation of NF-κB and C-jun. All of these findings suggest that sorafenib exerts an inhibitory effect on AA rats in vivo via AA FLS apoptotic induction, which has potential therapeutic implications for RA.

Research-based versus clinical serum creatinine measurements and the association of acute kidney injury with subsequent kidney function: findings from the Chronic Renal Insufficiency Cohort study.

BACKGROUND: Observational studies relying on clinically obtained data have shown that acute kidney injury (AKI) is linked to accelerated chronic kidney disease (CKD) progression. However, prior reports lacked uniform collection of important confounders such as proteinuria and pre-AKI kidney function trajectory, and may be susceptible to ascertainment bias, as patients may be more likely to undergo kidney function testing after AKI. METHODS: We studied 444 adults with CKD who participated in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study and were concurrent members of a large integrated healthcare delivery system. We estimated glomerular filtration rate (eGFR) trajectories using serum creatinine measurements from (i) the CRIC research protocol (yearly) and (ii) routine clinical care. We used linear mixed effects models to evaluate the associations of AKI with acute absolute change in eGFR and post-AKI eGFR slope, and explored whether these varied by source of creatinine results. Models were adjusted for demographic characteristics, diabetes status and albuminuria. RESULTS: During median follow-up of 8.5 years, mean rate of eGFR loss was -0.31 mL/min/1.73 m2/year overall, and 73 individuals experienced AKI (55% Stage 1). A significant interaction existed between AKI and source of serum creatinine for acute absolute change in eGFR level after discharge; in contrast, AKI was independently associated with a faster rate of eGFR decline (mean additional loss of -0.67 mL/min/1.73 m2/year), which was not impacted by source of serum creatinine. CONCLUSIONS: AKI is independently associated with subsequent steeper eGFR decline regardless of the serum creatinine source used, but the strength of association is smaller than observed in prior studies after taking into account key confounders such as pre-AKI eGFR slope and albuminuria.

Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway.

Studies have indicated that oxidative stress plays a crucial role in the development of Parkinson's disease (PD) and other neurodegenerative conditions. Research has also revealed that nuclear factor erythroid 2-related factor 2 (Nrf2) triggers the expression of antioxidant genes via a series of antioxidant response elements (AREs), thus preventing oxidative stress. Thymoquinone (TQ) is the bioactive component of Nigella sativa, a medicinal plant that exhibits antioxidant and neuroprotective effects. In the present study we examined whether TQ alleviates in vivo and in vitro neurodegeneration induced by 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by acting as an activator of the Nrf2/ARE cascade. We showed that TQ significantly reduced MPP+-mediated cell death and apoptosis. Moreover, TQ significantly elevated the nuclear translocation of Nrf2 and significantly increased the subsequent expression of antioxidative genes such as Heme oxygenase 1 (HO-1), quinone oxidoreductase (NQO1) and Glutathione-S-Transferase (GST). The application of siRNA to silence Nrf2 led to an abolishment in the protective effects of TQ. We also found that the intraperitoneal injection of TQ into a rodent model of PD ameliorated oxidative stress and effectively mitigated nigrostriatal dopaminergic degeneration by activating the Nrf2-ARE pathway. However, these effects were inhibited by the injection of a lentivirus wrapped Nrf2 siRNA (siNrf2). Collectively, these findings suggest that TQ alleviates progressive dopaminergic neuropathology by activating the Nrf2/ARE signaling cascade and by attenuating oxidative stress, thus demonstrating that TQ is a potential novel drug candidate for the treatment of PD.

[Effect on p53 and caspase-3 of hippocampal neuron in the rats with cerebral ischemia-reperfusion injury treated with electroacupuncture preconditioning at the acupoints on the basis of biao and ben relationship].

OBJECTIVE: To explore the protective effect and apoptosis-related mechanism of electroacupuncture (EA) preconditioning in the rats with cerebral ischemia-reperfusion injury. METHODS: Sixty male SD rats, 3 months old, at SPF grade were randomized into a sham-operation group, an ischemia-reperfusion group and an EA preconditioning group, 20 rats in each one. In the ischemia-reperfusion group and EA preconditioning group, the modified MCAO suture-occlusion method was adopted to exert ischemia for 2 h and reperfusion for 3 h, and thus, the models of focal cerebral ischemia-reperfusion injury were prepared on the right side. In the sham-operation group, the right common carotid artery was separated and no more management was given. In the EA preconditioning group, EA at "Baihui" (GV 20), "Shenshu" (BL 23) and "Sanyinjiao" (SP 6) was provided before modeling, with disperse-dense wave, at 2 Hz/100 Hz, 1 mA in intensity. The stimulation for 15 min was taken as one unit (meaning electric stimulation for 10 min and needle retaining for 5 min without electric stimulation). Such preconditioning was repeated continuously for 4 times, totally for 1 h. The neuroethologic condition was assessed in 3 h of reperfusion in each group. TTC staining method was used to determine the percentage of cerebral infarction zone, TUNEL method was to determine the apoptosis index (AI) in hippocampal neuron and the immunohistochemical method (IHC) was to determine the protein expression of p53 and caspase-3. RESULTS: Compared with the sham-operation group, the neuroethologic score, the percentage of cerebral infarction zone and neuronal AI were all increased obviously in the ischemia-reperfusion group (all P<0.01). Compared with the ischemia-reperfusion group, the neuroethologic score, the percentage of cerebral infarction zone and neuronal AI were all reduced obviously in the EA preconditioning group (all P<0.01). p53's nuclei and caspase-3's cytoplasms were stained. The positive cells of both of them were brown-yellow in color. In the sham-operation group, the structure of the right hippocampal CA3 neurons of rats was clear, with few positive cells. In the ischemia-perfusion group, the positive expressions of p53 and caspase-3 in the right hippocampal CA3 were increased obviously (P<0.01). Compared with the ischemia-reperfusion group, the positive expressions of caspase-3 and p53 in the right hippocampal CA3 were significantly reduced in the EA preconditioning group (P<0.01). CONCLUSION: Electroacupuncture preconditioning relieves ischemic injury in brain tissue of rats probably through inhibiting the expressions of p53 and caspase-3 to resisting neuronal apoptosis.

Aroma binding and stability in brewed coffee: A case study of 2-furfurylthiol.

The aroma stability of fresh coffee brew was investigated during storage over 60 min, there was a substantial reduction in available 2-furfurylthiol (2-FFT) (84%), methanethiol (72%), 3-methyl-1H-pyrole (68%) and an increase of 2-pentylfuran (65%). It is proposed that 2-FFT was reduced through reversible chemical binding and irreversible losses. Bound 2-FFT was released after cysteine addition, thereby demonstrating that a reversible binding reaction was the dominant mechanism of 2-FFT loss in natural coffee brew. The reduction in available 2-FFT was investigated at different pH and temperatures. At high pH, the reversible binding of 2-FFT was shown to protect 2-FFT from irreversible losses, while irreversible losses led to the reduction of total 2-FFT at low pH. A model reaction system was developed and a potential conjugate, hydroxyhydroquinone, was reacted with 2-FFT. Hydroxyhydroquinone also showed 2-FFT was released after cysteine addition at high pH.

Effect of Gua Sha therapy on patients with diabetic peripheral neuropathy: A randomized controlled trial.

OBJECTIVE: To examine the effect of Gua Sha therapy in the treatment of diabetic peripheral neuropathy (DNP). DESIGN: An open-label randomized controlled study was conducted with usual care as the control (60 subjects in Gua Sha group and 59 subjects in usual care group). Outcome measures included Toronto Clinical Scoring System (TCSS), Vibration Perception Threshold (VPT), Ankle Brachial Index (ABI), and fasting plasma glucose (FPG). There were 12 consecutive sessions of Gua Sha, one session per week. RESULTS: After the first cycle of Gua Sha intervention, only performance of sensory function measured by the VPT, and peripheral artery disease symptoms by the ABI were statistically significant differences between the two groups (both P values < 0.01), and the total TCSS score and the FPG level were no group differences (P = 0.14, and 0.25, respectively). At the eight-week and 12-week post intervention assessment, Gua Sha therapy significantly reduced severity of neuropathy symptoms, improved performance of sensory function, reduced peripheral artery disease, and better controlled plasma glucose by comparing with the control group (all P values < 0.01). The changes of mean scores of TCSS, VPT, ABI and the plasma glucose levels in the Gua Sha group showed a significant change from baseline to week 12, indicating that Gua Sha therapy induced progressive improvement in the management of DPN symptoms, sensory function, peripheral artery disease and glucose levels. No serious adverse events were reported in either arm. Gua Sha therapy in this study was effective, safe and well tolerated by patients. CONCLUSION: Gua Sha therapy appears to be effective at reducing the severity of DPN in a clinically relevant dimension, and at improving other health outcomes in patients with DPN. While this study found that Gua Sha therapy is a promising treatment in reducing the symptoms of patients with DPN, further, larger sample studies are required to confirm the effects of Gua Sha therapy in patients with DPN.

Experimental research into the potential therapeutic effect of GYY4137 on Ovariectomy-induced osteoporosis.

BACKGROUND: Evidence has shown that endogenous H2S plays an important role in the physiological and pathophysiological processes of many organs. The study aimed to explore whether exogenous H2S has a potential therapeutic effect on a rat ovariectomy-induced model of osteoporosis. METHODS: The OVX osteoporosis model was established in female Sprague-Dawley rats by full bilateral ovariectomy. The rats were randomly divided into four groups, with the two experimental groups receiving an intraperitoneal injection of GYY4137 or sodium alendronate. The level of H2S in the plasma was determined and common laboratory indicators to diagnose osteoporosis, such as alkaline phosphatase (ALP) activity and the levels of osteocalcin (OCN), calcitonin, parathyroid hormone and leptin were measured. The bone mineral density (BMD) of the 4th and 5th lumbar vertebrae was measured using dual-energy X-ray absorptiometry. The maximum stress of femoral fracture was obtained through a three-point bending test of the femur. RESULTS: The OVX osteoporosis model was successfully established. GYY4137 was injected to increase the level of H2S in the plasma in one group, designated OVX-GYY during the observation period (p < 0.05). At 12 weeks, the BMD value of the fourth lumbar vertebra in the OVX-GYY group had increased (p < 0.05). The BMD femur value in the OVX-vehicle group had decreased (p < 0.05). Bilateral ovariectomy leads to biochemical disorders related to bone metabolism and hormone levels in rat plasma (all p < 0.05). Ovariectomy also reduced blood calcium, blood phosphate and calcitonin, and increased parathyroid hormone and leptin. The opposite results were obtained for the groups with alendronate sodium or GYY4137 treatment (all p < 0.05). CONCLUSIONS: Through the slow release of H2S, GYY4137 did an excellent job of simulating endogenous neuroendocrine gaseous signaling molecules. Exogenous H2S had a regulatory effect on osteoporosis in ovariectomized rats, showing potential value for the treatment of human postmenopausal osteoporosis.