Riboflavin ameliorates intestinal inflammation via immune modulation and alterations of gut microbiota homeostasis in DSS-colitis C57BL/6 mice.

While there have been advancements in understanding the direct and indirect impact of riboflavin (B2) on intestinal inflammation, the precise mechanisms are still unknown. This study focuses on evaluating the effects of riboflavin (B2) supplementation on a colitis mouse model induced with 3% dextran sodium sulphate (DSS). We administered three different doses of oral B2 (VB2L, VB2M, and VB2H) and assessed its impact on various physiological and biochemical parameters associated with colitis. Mice given any of the three doses exhibited relative improvement in the symptoms and intestinal damage. This was evidenced by the inhibition of the pro-inflammatory cytokines TNF-α, IL-1ß, and CALP, along with an increase in the anti-inflammatory cytokine IL-10. B2 supplementation also led to a restoration of oxidative homeostasis, as indicated by a decrease in myeloperoxidase (MPO) and malondialdehyde (MDA) levels and an increase in reduced glutathione (GSH) and catalase (CAT) activities. B2 intervention showed positive effects on intestinal barrier function, confirmed by increased expression of tight junction proteins (occludin and ZO-1). B2 was linked to an elevated relative abundance of Actinobacteriota, Desulfobacterota, and Verrucomicrobiota. Notably, Verrucomicrobiota showed a significant increase in the VB2H group, reaching 15.03% relative abundance. Akkermansia exhibited a negative correlation with colitis and might be linked to anti-inflammatory function. Additionally, a remarkable increase in n-butyric acid, i-butyric acid, and i-valeric acid was reported in the VB2H group. The ameliorating role of B2 in gut inflammation can be attributed to immune system modulation as well as alterations in the gut microbiota composition, along with elevated levels of fecal SCFAs.

Manipulation of co-pelletization for Chlorela vulgaris harvest by treatment of Aspergillus niger spore.

The co-pelletization of microalgae with filamentous fungi was a promising approach for microalgae harvest. However, the real conditions of microalgae growth limited the arbitrary optimization of co-pellets formation with filamentous fungi. Therefore, it is urgent to develop an approach to manipulate the co-pelletization through treatment of A. niger spores. In this study, Aspergillus niger and Chlorella vulgaris were used as the model species of filamentous fungi and microalgae to investigate co-pellets formation using A. niger spores after by different pH solutions treatment, swelling, snailase treatment. The importance of spore treatments on C. vulgaris harvest in sequence was claimed based on response surface methodology analysis. The pH solutions treatment, swelling, snailase treatment of A. niger spore contributed 21.0%, 10.5%, 40.7% of harvest ratio of C. vulgaris respectively, which guided the application of spore treatment into co-pelletization. Treatment of spore was showed as an efficient approach to manipulate co-pelletization for microalgae harvest in diverse microalgae condition. This results promoted the application of co-pelletization technology in microalgae harvest of various conditions.

Response of Rhizosphere Bacterial Communities to Near-Natural Forest Management and Tree Species within Chinese Fir Plantations.

Near-natural forest management plays an important role in the maintenance of the long-term productivity and soil fertility of plantations. We conducted high-throughput absolute quantitative sequencing of 16S rRNA genes to compare the structures and diversity of rhizosphere soil bacterial communities among a pure Chinese fir (Cunninghamia lanceolata) plantation (S), a Cunninghamia lanceolata-Castanopsis hystrix-Michelia hedyosperma mixed plantation (SHX), and a Cunninghamia lanceolata-Castanopsis fissa mixed plantation (SD). The results revealed that near-natural forest management improved the rhizosphere soil properties of Chinese fir, especially the phosphorus content. Rhizosphere soil bacterial communities of Chinese fir in SHX and SD contained higher total absolute abundances and more unique operational taxonomic units (OTUs) than the pure plantation forest. Planctomycetes and Actinobacteria were abundant in SD, and Actinobacteria were enriched in SHX. The tree species also had an impact on the rhizosphere soil bacterial communities. For the rhizosphere soils of different tree species of SHX, the available phosphorus (AP) content of the rhizosphere of Chinese fir significantly surpassed those of Castanopsis hystrix and Michelia hedyosperma. Bacteria related to nitrogen fixing, such as Burkholderiales and Rhizobiales, were more abundant in Chinese fir in SD than in Castanopsis fissa. Acdiobacteria and Proteobacteria underpinned the differences found in the compositions of soil bacteria. The pH and soil organic matter were key variables influencing the rhizosphere soil bacterial communities. Our results demonstrated that in Chinese fir plantations, 12 years of near-natural management of introduced broad-leaved tree species can drive alterations of the physicochemical characteristics, bacterial community structure, and composition of rhizosphere soil, with tree species identity further influencing the rhizosphere soil bacterial community. IMPORTANCE Near-natural forest management is an important way to change the soil fertility decline and productivity reduction of pure Chinese fir plantations. At present, many detailed studies have been carried out on the impact of near-natural forest management on Chinese fir plantations at home and abroad. However, there are still few studies on the response of rhizosphere bacterial communities to near-natural forest management. Our study determined absolute quantities of Chinese fir rhizosphere bacterial communities in different mixed patterns. The results underscore the importance of near-natural forest management for Chinese fir plantation rhizosphere bacterial communities and provide new information on soil factors that affect rhizosphere bacterial communities in South China.

Integrated miRNA and mRNA omics reveal dioscin suppresses migration and invasion via MEK/ERK and JNK signaling pathways in human endometrial carcinoma in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonatum sibiricum Redouté (PS, also called Huangjing in traditional Chinese medicine), is a perennial herb as homology of medicine and food. According to the traditional Chinese medicine theory "Special Records of Famous Doctors", its functions include invigorating qi and nourishing yin, tonifying spleen and kidney. Traditionally, qi and blood therapy has been believed as most applicable to the treatment of uterine disease. The current research has focused on the effect and mechanism of dioscin, the main active component of PS, on Endometrial carcinoma (EC). AIM OF THE STUDY: To study the efficacy of dioscin on proliferation and migration of Endometrial carcinoma cell line, we conducted experiments by using xenograft model and Ishikawa cells, and explored the potential molecular mechanism. MATERIALS AND METHODS: mRNA and miRNA omics techniques were employed to investigate the regulatory mechanism of dioscin on EC Ishikawa cells. Based on in vivo and in vitro experiments, cell clone formation, cell scratching, Transwell, H&E staining, immunohistochemistry, q-PCR, and Western blot techniques were used to determine the molecular effects and mechanisms of dioscin on cell migration. RESULTS: Integrated miRNA and mRNA omics data showed that 513 significantly different genes marked enrichment in MAPK signaling pathway. The in vivo data showed that dioscin (24 mg/kg) significantly inhibited tumor growth. The in vitro proliferation and invasiveness of dioscin on Ishikawa cells showed that dioscin could significantly decrease the colony numbers, and suppress the Ishikawa cell wound healing, migration and invasion. Molecular data revealed that dioscin decreased the MMP2 and MMP9 expression in vitro and in vivo. The p-MEK, p-ERK, and p-JNK expression levels were also confirmed to be significantly reduced. Key regulators in the MAPK signaling pathway were further validated in xenograft tumors. CONCLUSION: Our data indicated that dioscin inhibited Ishikawa cell migration and invasion mediated through MEK/ERK and JNK signaling. More importantly, screened hub miRNAs and genes can be regarded as potential molecular targets for future EC treatment.

Evolutionary research trend of Polygonatum species: a comprehensive account of their transformation from traditional medicines to functional foods.

With the advances in Polygonatum research, there is a huge interest in harnessing the valuable functional ingredients of this genus with the potential for functional foods. This review emphasizes the different aspects of Ploygonatum based research starting from its bioactive compounds, their structural characterization, various extraction methods, as well as biological activities. In view of its integral use as an essential medicinal plant, our review emphasizes on its promising food applications both as an ingredient and as a whole food, and its improved health benefits with potential for agricultural and environmental relevance are also discussed. As we collated the recent research information, we present the main challenges and limitations of the current research trend in this area which can upgrade the further expansion of Polygonatum-related research that will strengthen its economic and accessible nutritional value in the food and health industries. By highlighting the need for the unattended species, this review not only fills existing research gaps, but also encourages the researchers to find new avenues for the natural production of bio-based functional materials and the development of highly functional and health-promoting foods for disease prevention and treatment.

Transcriptome and proteomics conjoint analysis reveal metastasis inhibitory effect of 6-shogaol as ferroptosis activator through the PI3K/AKT pathway in human endometrial carcinoma in vitro and in vivo.

Endometrial cancer remains as one of the widespread female malignancies despite the existing treatment measures mainly surgery, radiotherapy, and chemotherapy. In recent times, studies have focused on medicinal plants such as ginger due to its multifaceted characteristics compared to conventional medicine. 6-Shogaol is regarded as the main active compound of ginger participating in pharmacological activities and combating various health disorders, especially cancer. In our study, we compared the effects of 6-gingerol, 6-paradol, and 6-shogaol on Ishikawa cells, and found 6-shogaol as a more effective ingredient against Ishikawa cell proliferation. Moreover, its promoted ferroptosis, as a result, triggered mitochondrial morphologic alternation, as well as changed iron concentration, GSH and MDA levels. Furthermore, 6-Shogaol inhibited cell metastasis by influencing cell invasion and migration. Finally, 6-shogaol could trigger PI3K/AKT signaling pathways in vitro and in vivo confirmed by western blotting assay and immunohistochemical evaluation. These findings suggest that 6-shogaol can be used as promising functional food component in health diet and in drug target methods for endometrial cancer therapy.

[Neuromodulation: Past, Present, and Future].

Neuromodulation technology is one of the medical fields currently experiencing the most rapid development, witnessing a surge in the types of modulation techniques and a constant expansion of indications. Consequently, hundreds of thousands of patients with functional neurological disorders have benefited from the advancements in the field all over the world. Nevertheless, some challenges remain, for exmaple, the lack of a thorough understanding of the mechanism of neuromodulation, the long-standing controversy over the optimal targets of neuromodulation, the lack of reliable efficacy predictors, and the cumbersome and inefficient mode of postoperative programming. We anticipate that these issues will be resolved with the continued advancement in medical technology and the gradual revelation of the neural network mechanism of brain disorders. More individualized, precise, and intelligent neuromodulation technology will be the main direction of development in the future. Herein, we reviewed and commented on the evolution of neuromodulation technology, the current status of its applications, and its prospective development.

Gut modulatory effects of flaxseed derived Maillard reaction products in Sprague-Dawley rats during sub-chronic toxicity.

Our study aimed to understand the effects of Maillard reaction products (MRPs) intake on intestinal health, in vitro digestion, and fermentation metabolites in Sprague-Dawley (SD) rats. MRPs promoted the digestion of pepsin, but was not conducive to the subsequent in vitro digestion of trypsin. MRPs ingestion increased the propionate in intestine, but it could not change the branched-chain fatty acids (BCFAs) and short-chain fatty acids (SCFAs). However, MRPs ingestion led to an increase in the Lactobacillus abundance in gut. In the high-dose groups, the abundance of genes in partial amino acid and monosaccharide metabolism increased, while in lipid metabolism decreased compared with the middle dose groups. Therefore, the absorption of MRPs was lowered than that of protein and carbohydrates. Through functional predictive analysis, our study could reveal the effects of long-term intake of MRPs on intestinal health in SD rats.

Functional and emulsification characteristics of phospholipids and derived o/w emulsions from peony seed meal.

Peony seed phospholipids (PPLs), a kind of multifunctional plant-like phospholipids were extracted from peony seed meal. We investigated the functional properties of PPLs and compared their emulsification performance in corn oil-peony seed oil o/w emulsion systems with that of soy lecithin (DPLs). The PPLs were characterized with the higher content of phosphatidylcholine (PC) (416 ± 28 mg/g) and lyso-phosphatidylcholine (LPC) (43 ± 14 mg/g) fractions, and lower content of phosphatidylethanolamine (PE) (71 ± 13 mg/g). The polyunsaturated fatty acids showed higher content (83.25%), with the highest content of linoleic acid (46.05%) in PPLs. PPLs-emulsions showed smaller average particle size and higher loaded peony seed oil content at pH 5, temperature 50 °C, and about 60% corn oil content. PPLs-emulsions imparted better hydroxyl radical scavenging efficiency and reducing power than DPLs. Our results suggest that PPLs can be used as emulsifiers with improved antioxidant properties.

Riboflavin Bioenriched Soymilk Alleviates Oxidative Stress Mediated Liver Injury, Intestinal Inflammation, and Gut Microbiota Modification in B2 Depletion-Repletion Mice.

Epidemiological evidence emphasizes that ariboflavinosis can lead to oxidative stress, which in turn may mediate the initiation and progression of liver injury and intestinal inflammation. Although vitamin B2 has gained worldwide attention for its antioxidant defense, the relationship between B2 status, oxidative stress, inflammatory response, and intestinal homeostasis remains indistinct. Herein, we developed a B2 depletion-repletion BALB/c mice model to investigate the ameliorative effects of B2 bioenriched fermented soymilk (B2FS) on ariboflavinosis, accompanied by oxidative stress, inflammation, and gut microbiota modulation in response to B2 deficiency. In vivo results revealed that the phenotypic ariboflavinosis symptoms, growth rate, EGRAC status, and hepatic function reverted to normal after B2FS supplementation. B2FS significantly elevated CAT, SOD, T-AOC, and compromised MDA levels in the serum, simultaneously up-regulated Nrf2, CAT, and SOD2, and down-regulated Keap1 gene in the colon. The histopathological characteristics revealed significant alleviation in the liver and intestinal inflammation, confirmed by the downregulation of inflammatory (IL-1ß and IL-6) and nuclear transcription (NF-κB) factors after B2FS supplementation. B2FS also increased the abundance and diversity of gut microbiota, increased the relative abundance of Prevotella and Absiella, as well as decreased Proteobacteria, Fusobacteria, Synergistetes, and Cyanobacteria in strong conjunction with antioxidant, anti-inflammatory properties, and gut homeostasis along with the remarkable increase in cecal SCFAs content. We hereby reveal that B2FS can effectively alleviate deleterious ariboflavinosis associated with oxidative stress mediated liver injury, chronic intestinal inflammation, and gut dysbiosis in the B2 depletion-repletion mice model via activation of the Nrf2 signaling pathway.

CACA Guidelines for Holistic Integrative Management of Breast Cancer.

Purpose: Breast cancer is now the most common malignant tumor worldwide. About one-fourth of female cancer patients all over the world suffer from breast cancer. And about one in six female cancer deaths worldwide is caused by breast cancer. In terms of absolute numbers of cases and deaths, China ranks first in the world. The CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in China. Methods: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to classify evidence and consensus. Results: The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer, breast cancer screening, breast cancer diagnosis, early breast cancer treatment, advanced breast cancer treatment, follow-up, rehabilitation, and traditional Chinese medicine treatment of breast cancer patients. Conclusion: We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.

Bioaccumulation characteristics and acute toxicity of uranium in Hydrodictyon reticulatum: An algae with potential for wastewater remediation.

The bioaccumulation characteristics and acute toxicity of uranium (U) to Hydrodictyon reticulatum were studied to provide reference for further mechanism and application research. According to an analysis using visual MINTEQ software, the pH change caused by the photosynthesis of H. reticulatum leads to U remaining mainly in the species of UO2(OH)3-. Fourier transform infrared spectrometer (FTIR) and transmission electron microscope (TEM) analysis showed that the bioaccumulation of U was related to the amino and carboxyl groups, resulting in cell wall damage. Using innovative cell staining microscopic observation techniques, U was mainly compartmentalized in vacuoles and pyrenoid; chlorophyll, soluble protein, dehydrogenase activity, and other physiological responses were closely related to the U stress concentration. Especially here, the change trend of the specific activity and specific growth rate of dehydrogenase was consistent, showing low concentration promotion and high concentration inhibition. Combined with the toxic response of the two, the half inhibitory dose for 72 h was determined to be about 30 mg L-1. When bioaccumulation equilibrium is reached at 72 h, the maximum tolerance concentration of U without affecting the easy collection characteristics of the algae is 30 mg L-1, and the maximum U bioaccumulation capacity was able to reach 24.47 ± 0.86 mg g-1 by dry biomass.

Severe complications and management of a patient with myasthenia gravis undergoing anterior cervical spinal surgery: a case report.

Surgical management of patients with comorbid long-term myasthenia gravis (MG) is particularly challenging and MG thus represents an independent risk factor for perioperative complications. However, few studies have reported on the perioperative assessment, prevention measures, and risks in MG patients undergoing major surgery, especially for anterior cervical spine surgery. We herein report the rare case of a 62-year-old man with a 20-year history of MG, who was admitted to our hospital with diagnosis of degenerative cervical spondylosis. He safely underwent anterior cervical corpectomy of C4, discectomy of C5-6, and fusion of C3-6. Intraoperative motor evoked potential was recorded to detect significant improvement after decompression. However, the patient suffered from progressive dysphagia, bucking, and hyperpyrexia 20 days after the initial operation. Imaging revealed titanium cage sliding and graft dislodgement. Secondary surgery was performed for posterior internal fixation from C2-7 and anterior revision from C3-6 after Halo-Vest traction, antibiotic treatment, and immunoglobulin therapy. He underwent a series of postoperative treatments, including cervicothoracolumbosacral orthosis, atomization inhalation, chest physiotherapy, antibiotics, and nutritional support. His condition improved markedly and he had no recurrence of symptoms during the 6-month follow-up. It is the rare reported case of anterior cervical spinal surgery in a patient with MG. This rare case indicates a relative contraindication to anterior-only approaches especially with multiple levels for MG patients with cervical spondylosis. Posterior approach, intraoperative monitoring, osteoporosis, postoperative strong brace protection, and supportive management should be considered for patients who were on large doses of steroids for long duration of time, given the lack of sufficient bone mineral density.

Formononetin reshapes the gut microbiota, prevents progression of obesity and improves host metabolism.

Formononetin (FMNT) is an isoflavone that has been studied for its anti-hyperglycemic and anti-diabetic effects. However, the effect of FMNT on gut dysbiosis and metabolic complications associated with western-style diet consumption has not been reported yet. This study aimed to investigate how FMNT can reshape the gut microbiota at a specific dosage and ameliorate the symptoms of obesity-related metabolic disorders in both genders. Results indicate that FMNT at 60 mg per kg bodyweight dosage can effectively control body weight, hyperglycemia, and insulin resistance, leptin levels and improve HDL to LDL ratio. FMNT treatment suppressed Porphyromonadaceae (Uncultured Alistipes) and augmented maximum genera from families Lachnospiraceae and Clostridiacea, but at species level, formononetin increased Clostridium aldenense, Clostridiaceae unclassified, Eubacterium plexicaum; acetate and butyrate-producing bacteria. Moreover, formononetin regulated the expression of specific liver miRNA involved in obesity and down-regulated mRNA expression levels of pro-inflammatory cytokines IL-6, IL-22 and TNF-α. Additionally, FMNT maintained intestinal membrane integrity by regulating the expression of Muc-2 and occludin. Our findings indicate that FMNT could be a potential prebiotic that can effectively regulate the gut microbiota, improve host metabolism and systemic inflammation, and prevent deleterious effects of a western-style diet by elevating acetate lactate and lactate butyrate producers.

MXene and black phosphorus based 2D nanomaterials in bioimaging and biosensing: progress and perspectives.

Bioimaging and biosensing have garnered interest in early cancer diagnosis due to the ability of gaining in-depth insights into cellular functions and providing a wide range of diagnostic parameters. Emerging 2D materials of multielement MXenes and monoelement black phosphorous nanosheets (BPNSs) with unique intrinsic physicochemical properties such as a tunable bandgap and layer-dependent fluorescence, high carrier mobility and transport anisotropy, efficient fluorescence quenching capability, desirable light absorption and thermoelastic properties, and excellent biocompatibility and biosafety properties provide promising nano-platforms for bioimaging and biosensing applications. In view of the growing attention on the rising stars of the post-graphene age in the progress of bioimaging and biosensing, and their common feature characteristics as well as complementarity for constructing complexes, the main objective of this review is to reveal the recent advances in the design of MXene or BPNS based nanoplatforms in the field of bioimaging and biosensing. The preparation and surface functionalization methods, biosafety, and other important aspects of bioimaging and biosensing applications of MXenes and BPNSs have been assessed systematically, along with highlighting the main challenges in further biomedical application. The review not only focuses on the advancements in 2D materials for use in bioimaging and biosensing but also assesses the possibility of their future potential in bioapplications.

Preparation and characterization of clove essential oil loaded nanoemulsion and pickering emulsion activated pullulan-gelatin based edible film.

The clove essential oil (CEO) loaded nano and pickering emulsions prepared with Tween 80 and whey protein isolate/inulin mixture, respectively were incorporated into pullulan-gelatin film base fluid at three levels (0.2%, 0.4%, and 0.6%). The droplet sizes of NE and PE loaded with CEO were 15.93 nm and 266.9 nm, respectively. The PDI of CEOs with stable NE and PE were 0.262 and 0.259, respectively. Our results showed the improved compatibility between pullulan-gelatin and essential oil-loaded nanocarriers. The active film composed of PE carrier had the structural characteristics of high density, low water content, and low permeability, thus exhibiting excellent mechanical properties, water barrier properties, and appreciable antioxidant activities. Compared with NE, it was found that the CEO-loaded PE showed slow-release profile in the film sample. The prepared active film containing PE possessed a great potential to be used as effective and natural alternatives for active food packaging.

Effect of grape seed power on the structural and physicochemical properties of wheat gluten in noodle preparation system.

Noodles were prepared using wheat flour supplemented with 1%, 3%, and 5% grape seed power (GSP). The farinograph properties of wheat flour, the textural properties of the dough, and thermal properties of the gluten were determined. The microstructure was analyzed by scanning electron and atomic force microscopy, and the effects of the addition of GSP on the physicochemical and structural properties (free sulfhydryl content, surface hydrophobic region, and secondary structure) of wheat gluten protein were analyzed. 1% GSP promoted the aggregation of gluten proteins by promoting hydrophobic interactions and hydrogen bonding, thus enhanced the noodle quality. Whereas, 3% and 5% GSP addition disrupted the disulfide bonds between gluten protein molecules and formed macromolecular aggregates linked to gluten proteins through non-covalent bonds and hydrophobic interactions, which prevented the formation of the gluten protein reticulation structure. Our study emphasized the interaction between wheat proteins and GSP in noodle making dough.

Asparanin A inhibits cell migration and invasion in human endometrial cancer via Ras/ERK/MAPK pathway.

Asparanin A (AA), a natural compound present in vegetables and medicinal herbs like Asparagus officinalis L., has been investigated extensively for its pharmacological attributes. So far, the effect of AA on endometrial cancer (EC) cell migration and invasion has not been explored. Herein, we elucidated the anti-metastasis mechanism of AA on Ishikawa cells based on miRNA-seq and mRNA-seq integrated analyses. AA treatment led to altered miRNAs expression in Ishikawa cells and inhibited the cell wound healing, cell migration and invasion. Gene Ontology and KEGG enrichment analyses showed that the target genes of different expression miRNAs were significantly enriched in Ras, Rap1 and MAPK signaling pathways. Further verification of these changes via qRT-PCR and Western blot assays in vitro and in vivo demonstrated that AA could suppress human EC cell migration and invasion through Ras/ERK/MAPK pathway. Furthermore, top two miRNAs (miR-6236-p5 and miR-12136_R+8) and top three target genes (KITLG, PDGFD, and NRAS) were identified as functional hub miRNAs and genes through miRNA-target gene network analysis. Our data presented a holistic approach to comprehend the anti-metastatic role of AA in EC after in vitro and in vivo analyses.

A recent update on the multifaceted health benefits associated with ginger and its bioactive components.

Due to recent lifestyle shifts and health discernments among consumers, synthetic drugs are facing the challenge of controlling disease development and progression. Various medicinal plants and their constituents are recognized for their imminent role in disease management via modulation of biological activities. At present, research scholars have diverted their attention on natural bioactive entities with health-boosting perception to combat the lifestyle-related disarrays. In particular, Zingiber officinale is a medicinal herb that has been commonly used in food and pharmaceutical products. Its detailed chemical composition and high value-added active components have been extensively studied. In this review, we have summarized the pharmacological potential of this well-endowed chemo preventive agent. It was revealed that its functionalities are attributed to several inherent chemical constituents, including 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 6-hydroshogaol, and oleoresin, which were established through many studies (in vitro, in vivo, and cell lines). In this review, we also focused on the therapeutic effects of ginger and its constituents for their effective antioxidant properties. Their consumption may reduce or delay the progression of related diseases, such as cancer, diabetes, and obesity, via modulation of genetic and metabolic activities. The updated data could elucidate the relationship of the extraction processes with the constituents and biological manifestations. We have collated the current knowledge (including the latest clinical data) about the bioactive compounds and bioactivities of ginger. Their detailed mechanisms, which can lay foundation for their food and medical applications are also discussed.

Subthalamic Nucleus Deep Brain Stimulation Modulates 2 Distinct Neurocircuits.

OBJECTIVE: Current understanding of the neuromodulatory effects of deep brain stimulation (DBS) on large-scale brain networks remains elusive, largely due to the lack of techniques that can reveal DBS-induced activity at the whole-brain level. Using a novel 3T magnetic resonance imaging (MRI)-compatible stimulator, we investigated whole-brain effects of subthalamic nucleus (STN) stimulation in patients with Parkinson disease. METHODS: Fourteen patients received STN-DBS treatment and participated in a block-design functional MRI (fMRI) experiment, wherein stimulations were delivered during "ON" blocks interleaved with "OFF" blocks. fMRI responses to low-frequency (60Hz) and high-frequency(130Hz) STN-DBS were measured 1, 3, 6, and 12 months postsurgery. To ensure reliability, multiple runs (48 minutes) of fMRI data were acquired at each postsurgical visit. Presurgical resting-state fMRI (30 minutes) data were also acquired. RESULTS: Two neurocircuits showed highly replicable, but distinct responses to STN-DBS. A circuit involving the globus pallidus internus (GPi), thalamus, and deep cerebellar nuclei was significantly activated, whereas another circuit involving the primary motor cortex (M1), putamen, and cerebellum showed DBS-induced deactivation. These 2 circuits were dissociable in terms of their DBS-induced responses and resting-state functional connectivity. The GPi circuit was frequency-dependent, selectively responding to high-frequency stimulation, whereas the M1 circuit was responsive in a time-dependent manner, showing enhanced deactivation over time. Finally, activation of the GPi circuit was associated with overall motor improvement, whereas M1 circuit deactivation was related to reduced bradykinesia. INTERPRETATION: Concurrent DBS-fMRI using 3T revealed 2 distinct circuits that responded differentially to STN-DBS and were related to divergent symptoms, a finding that may provide novel insights into the neural mechanisms underlying DBS. ANN NEUROL 2020;88:1178-1193.