Sorghum Grain Polyphenolic Extracts Demonstrate Neuroprotective Effects Related to Alzheimer's Disease in Cellular Assays.

Sorghum grain contains high levels and a diverse profile of polyphenols (PPs), which are antioxidants known to reduce oxidative stress when consumed in the diet. Oxidative stress leading to amyloid-ß (Aß) aggregation, neurotoxicity, and mitochondrial dysfunction is implicated in the pathogenesis of Alzheimer's disease (AD). Thus, PPs have gained attention as possible therapeutic agents for combating AD. This study aimed to (a) quantify the phenolic compounds (PP) and antioxidant capacities in extracts from six different varieties of sorghum grain and (b) investigate whether these PP extracts exhibit any protective effects on human neuroblastoma (BE(2)-M17) cells against Aß- and tau-induced toxicity, Aß aggregation, mitochondrial dysfunction, and reactive oxygen species (ROS) induced by Aß and tert-butyl hydroperoxide (TBHP). PP and antioxidant capacity were quantified using chemical assays. Aß- and tau-induced toxicity was determined using the 3-(4,5-dimenthylthiazol-2-yl)-2,5-dimethyltetrazolium bromide (MTS) assay. The thioflavin T (Th-T) assay assessed anti-Aß aggregation. The dichlorodihydrofluorescein diacetate (DCFDA) assay determined the levels of general ROS and the MitoSOX assay determined the levels of mitochondrial superoxide. Sorghum varieties Shawaya short black-1 and IS1311C possessed the highest levels of total phenolics, total flavonoids, and antioxidant capacity, and sorghum varieties differed significantly in their profile of individual PPs. All extracts significantly increased cell viability compared to the control (minus extract). Variety QL33 (at 2000 µg sorghum flour equivalents/mL) showed the strongest protective effect with a 28% reduction in Aß-toxicity cell death. The extracts of all sorghum varieties significantly reduced Aß aggregation. All extracts except that from variety B923296 demonstrated a significant (p ≤ 0.05) downregulation of Aß-induced and TBHP-induced ROS and mitochondrial superoxide relative to the control (minus extract) in a dose- and variety-dependent manner. We have demonstrated for the first time that sorghum polyphenolic extracts show promising neuroprotective effects against AD, which indicates the potential of sorghum foods to exert a similar beneficial property in the human diet. However, further analysis in other cellular models and in vivo is needed to confirm these effects.

The Role of Diet and Gut Microbiota in Alzheimer's Disease.

Alzheimer's disease (AD), the most prevalent form of dementia, is characterized by the accumulation of amyloid-beta (Aß) plaques and hyperphosphorylated tau tangles. Currently, Alzheimer's disease (AD) impacts 50 million individuals, with projections anticipating an increase to 152 million by the year 2050. Despite the increasing global prevalence of AD, its underlying pathology remains poorly understood, posing challenges for early diagnosis and treatment. Recent research suggests a link between gut dysbiosis and the aggregation of Aß, the development of tau proteins, and the occurrence of neuroinflammation and oxidative stress are associated with AD. However, investigations into the gut-brain axis (GBA) in the context of AD progression and pathology have yielded inconsistent findings. This review aims to enhance our understanding of microbial diversity at the species level and the role of these species in AD pathology. Additionally, this review addresses the influence of confounding elements, including diet, probiotics, and prebiotics, on AD throughout different stages (preclinical, mild cognitive impairment (MCI), and AD) of its progression.

Neutrophils only die twice.

After apoptotic cell death begins neutrophils initiate NETosis, a second cell death program.

Effect of Virgin Coconut Oil Supplementation on Cognition of Individuals with Mild-to-Moderate Alzheimer's Disease in Sri Lanka (VCO-AD Study): A Randomized Placebo-Controlled Trial.

BACKGROUND: Virgin coconut oil (VCO) is a potential therapeutic approach to improve cognition in Alzheimer's disease (AD) due to its properties as a ketogenic agent and antioxidative characteristics. OBJECTIVE: This study aimed to investigate the effect of VCO on cognition in people with AD and to determine the impact of apolipoprotein E (APOE) ɛ4 genotype on cognitive outcomes. METHODS: Participants of this double-blind placebo-controlled trial (SLCTR/2015/018, 15.09.2015) were 120 Sri Lankan individuals with mild-to-moderate AD (MMSE = 15-25), aged > 65 years, and they were randomly allocated to treatment or control groups. The treatment group was given 30 mL/day of VCO orally and the control group, received similar amount of canola oil, for 24 weeks. The Mini-Mental Sate Examination (MMSE) and Clock drawing test were performed to assess cognition at baseline and at the end of the intervention. Blood samples were collected and analyzed for lipid profile and glycated hemoglobin (HbA1 C) levels.∥Results:There were no significant difference in cognitive scores, lipid profile, and HbA1 C levels between VCO and control groups post-intervention. The MMSE scores, however, improved among APOE ɛ4 carriers who had VCO, compared to non-carriers (2.37, p = 0.021). APOE ɛ4 status did not influence the cognitive scores in the control group. The attrition rate was 30%.∥Conclusion:Overall, VCO did not improve cognition in individuals with mild-to-moderate AD following a 24-week intervention, compared to canola oil. However, it improved the MMSE scores in APOE ɛ4 carriers. Besides, VCO did not compromise lipid profile and HbA1 C levels and is thus safe to consume.

An innate granuloma eradicates an environmental pathogen using Gsdmd and Nos2.

Granulomas often form around pathogens that cause chronic infections. Here, we discover an innate granuloma model in mice with an environmental bacterium called Chromobacterium violaceum. Granuloma formation not only successfully walls off, but also clears, the infection. The infected lesion can arise from a single bacterium that replicates despite the presence of a neutrophil swarm. Bacterial replication ceases when macrophages organize around the infection and form a granuloma. This granuloma response is accomplished independently of adaptive immunity that is typically required to organize granulomas. The C. violaceum-induced granuloma requires at least two separate defense pathways, gasdermin D and iNOS, to maintain the integrity of the granuloma architecture. This innate granuloma successfully eradicates C. violaceum infection. Therefore, this C. violaceum-induced granuloma model demonstrates that innate immune cells successfully organize a granuloma and thereby resolve infection by an environmental pathogen.

The effectiveness of high-intensity laser therapy in individuals with neck pain: a systematic review and meta-analysis.

OBJECTIVES: The primary objective of this meta-analysis was to determine whether high-intensity laser therapy (HILT) was effective in improving pain intensity, cervical range of motion (ROM), functional activity, and quality of life (QOL) in individuals with neck pain. DATA SOURCES: PubMed, PEDro, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from inception to March 26, 2022. STUDY SELECTION: Randomized controlled trials (RCTs) involving HILT for neck pain were selected. DATA EXTRACTION AND DATA SYNTHESIS: Two raters were independent in data extraction. The methodological quality was evaluated using the PEDro scale, and the level of evidence was assessed using the GRADE system. RevMan5.4 was used for meta-analysis. RESULTS: Eight RCTs were included and their PEDro scores were moderate to high. Compared with placebo, HILT was effective in improving pain intensity (SMD 2.12, 95%CI 1.24 to 3.00; moderate quality evidence), cervical flexion (SMD 1.31, 95%CI 0.27 to 2.35; moderate quality evidence), extension (SMD 1.43, 95%CI 0.24 to 2.63; moderate quality evidence), right lateral flexion (SMD 1.36, 95%CI 0.15 to 2.56; low-quality evidence). There was a trend of better outcome in functional activity after HILT (SMD 1.73, 95%CI -0.05 to 3.54; low quality evidence). LIMITATIONS: There was limited information available on QOL. CONCLUSION: HILT may be considered as an adjunctive treatment modality for neck pain. There was moderate quality evidence that HILT may improve pain intensity and cervical ROM in individuals with neck pain, but there was low quality evidence that HILT was not effective in improving functional activity. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021254078 CONTRIBUTION OF THE PAPER.

Dysregulated Rbfox2 produces aberrant splicing of CaV1.2 calcium channel in diabetes-induced cardiac hypertrophy.

BACKGROUND: L-type Ca2+ channel CaV1.2 is essential for cardiomyocyte excitation, contraction and gene transcription in the heart, and abnormal functions of cardiac CaV1.2 channels are presented in diabetic cardiomyopathy. However, the underlying mechanisms are largely unclear. The functions of CaV1.2 channels are subtly modulated by splicing factor-mediated alternative splicing (AS), but whether and how CaV1.2 channels are alternatively spliced in diabetic heart remains unknown. METHODS: Diabetic rat models were established by using high-fat diet in combination with low dose streptozotocin. Cardiac function and morphology were assessed by echocardiography and HE staining, respectively. Isolated neonatal rat ventricular myocytes (NRVMs) were used as a cell-based model. Cardiac CaV1.2 channel functions were measured by whole-cell patch clamp, and intracellular Ca2+ concentration was monitored by using Fluo-4 AM. RESULTS: We find that diabetic rats develop diastolic dysfunction and cardiac hypertrophy accompanied by an increased CaV1.2 channel with alternative exon 9* (CaV1.2E9*), but unchanged that with alternative exon 8/8a or exon 33. The splicing factor Rbfox2 expression is also increased in diabetic heart, presumably because of dominate-negative (DN) isoform. Unexpectedly, high glucose cannot induce the aberrant expressions of CaV1.2 exon 9* and Rbfox2. But glycated serum (GS), the mimic of advanced glycation end-products (AGEs), upregulates CaV1.2E9* channels proportion and downregulates Rbfox2 expression in NRVMs. By whole-cell patch clamp, we find GS application hyperpolarizes the current-voltage curve and window currents of cardiac CaV1.2 channels. Moreover, GS treatment raises K+-triggered intracellular Ca2+ concentration ([Ca2+]i), enlarges cell surface area of NRVMs and induces hypertrophic genes transcription. Consistently, siRNA-mediated knockdown of Rbfox2 in NRVMs upregulates CaV1.2E9* channel, shifts CaV1.2 window currents to hyperpolarization, increases [Ca2+]i and induces cardiomyocyte hypertrophy. CONCLUSIONS: AGEs, not glucose, dysregulates Rbfox2 which thereby increases CaV1.2E9* channels and hyperpolarizes channel window currents. These make the channels open at greater negative potentials and lead to increased [Ca2+]i in cardiomyocytes, and finally induce cardiomyocyte hypertrophy in diabetes. Our work elucidates the underlying mechanisms for CaV1.2 channel regulation in diabetic heart, and targeting Rbfox2 to reset the aberrantly spliced CaV1.2 channel might be a promising therapeutic approach in diabetes-induced cardiac hypertrophy.

Can dietary magnesium sources and buffer change the ruminal microbiota composition and fermentation of lactating dairy cows?

Magnesium oxide (MgO) is one of the most used Mg supplements in livestock. However, to avoid relying upon only one Mg source, it is important to have alternative Mg sources. Therefore, the objective of this study was to evaluate the effects of the interaction of two Mg sources with buffer use on the ruminal microbiota composition, ruminal fermentation, and nutrient digestibility in lactating dairy cows. Twenty lactating Holstein cows were blocked by parity and days in milk into five blocks with four cows each, in a 2 × 2 factorial design. Within blocks, cows were assigned to one of four treatments: 1) MgO; 2) MgO + Na sesquicarbonate (MgO+); 3) calcium-magnesium hydroxide (CaMgOH); 4) CaMgOH + Na sesquicarbonate (CaMgOH+). For 60 d, cows were individually fed a corn silage-based diet, and treatments were top-dressed. Ruminal fluid was collected via an orogastric tube, for analyses of the microbiota composition, volatile fatty acids (VFA), lactate, and ammonia nitrogen (NH3-N). The microbiota composition was analyzed using V4/16S rRNA gene sequencing, and taxonomy was assigned using the Silva database. Statistical analysis was carried out following the procedures of block design analysis, where block and cow were considered random variables. Effects of Mg source, buffer, and the interaction between Mg Source × Buffer were analyzed through orthogonal contrasts. There was no interaction effect of the two factors evaluated. There was a greater concentration of NH3-N, lactate, and butyrate in the ruminal fluid of cows fed with CaMg(OH)2, regardless of the buffer use. The increase in these fermentation intermediates/ end-products can be explained by an increase in abundance of micro-organisms of the genus Prevotella, Lactobacillus, and Butyrivibrio, which are micro-organisms mainly responsible for proteolysis, lactate-production, and butyrate-production in the rumen, respectively. Also, dietary buffer use did not affect the ruminal fermentation metabolites and pH; however, an improvement of the apparent total tract digestibility of dry matter (DM), organic matter (OM), neutral fiber detergent (NDF), and acid fiber detergent (ADF) were found for animals fed with dietary buffer. In summary, there was no interaction effect of buffer use and Mg source, whereas buffer improved total tract apparent digestibility of DM and OM through an increase in NDF and ADF digestibility and CaMg(OH)2 increased ruminal concentration of butyrate and abundance of butyrate-producing bacteria.

Magnesium oxide (MgO) is extensively used as a dietary magnesium (Mg) source in dairy cow diets. However, dairy operations can benefit from other Mg sources. Thus, we evaluated the replacement of dietary MgO with calcium­magnesium hydroxide (CaMg(OH)2) in diets with and without ruminal buffer and their effects on the ruminal microbiota composition, ruminal fermentation, and nutrient digestibility in lactating dairy cows. The study used 20 lactating Holstein cows that were blocked in groups of four and randomly assigned to one of the four treatments. The ruminal content, feed, feces, and urine were collected for analysis of the microbiota composition, ruminal fermentation, nitrogen metabolism, and apparent nutrient digestibility. There was no interaction effect of dietary buffer use and Mg source, while buffer improved total tract apparent digestibility of the dry matter and fiber components; CaMg(OH)2 increased the ruminal concentration of butyrate and the abundance of butyrate-producing bacteria. In summary, we conclude that using CaMg(OH)2 can improve ruminal fermentation regardless of buffer use, which indicates that we can take advantage of the mineral formulation in the diet to modulate the ruminal microbiota composition.

A new seed-feeding species of Hemicolpus Heller, 1895 from south Brazil and redescription of Hemicolpus abdominalis Hustache, 1938 (Coleoptera: Curculionidae: Conoderinae).

The genus Hemicolpus Heller, 1895 (Curculionidae: Conoderinae) currently includes six species: H. cubicus (Lacordaire) (Brazil); H. heteromorphus Hustache (Brazil); H. abdominalis Hustache (Bolivia, Brazil, and Paraguay); H. costaricensis Hespenheide (Costa Rica); H. randiae Hespenheide (El Salvador and Mexico) and H. prenai Hespenheide (El Salvador and Mexico). The known species are predispersal seed predators whose larvae feed and develop within fruits of Rubiaceae. Species from Central America have been reared from the fruits of Randia L. (Rubiaceae). In contrast, the only host plant known for the South American species, H. abdominalis, is Tocoyena formosa (Cham. & Schltdl.) K. Schum. (Rubiaceae), a plant species widely distributed in the Cerrado biome, occurring from southeast to north and northeast of Brazil. Here, we describe a seventh species of Hemicolpus, H. maragatensis Sanz-Veiga, Savaris & Leivas, sp. nov., morphologically close to H. abdominalis, associated with fruits of Randia ferox (Cham. & Schltdl.) DC. in the south of Brazil. Furthermore, we designate a lectotype and provide a redescription of H. abdominalis, including additional characters to differentiate it from H. maragatensis. For both species, we provide morphological descriptions of external and internal characters, including male and female genitalia illustrations, distribution data, and notes on the biology and host plant. A barcode region of the mitochondrial DNA is also included for both species adding genetic information to the species characterization and differentiation. We also provide an identification key for the species of the genus.

Structured foraging of soil predators unveils functional responses to bacterial defenses.

Predators and their foraging strategies often determine ecosystem structure and function. Yet, the role of protozoan predators in microbial soil ecosystems remains elusive despite the importance of these ecosystems to global biogeochemical cycles. In particular, amoebae-the most abundant soil protozoan predator of bacteria-remineralize soil nutrients and shape the bacterial community. However, their foraging strategies and their role as microbial ecosystem engineers remain unknown. Here, we present a multiscale approach, connecting microscopic single-cell analysis and macroscopic whole ecosystem dynamics, to expose a phylogenetically widespread foraging strategy, in which an amoeba population spontaneously partitions between cells with fast, polarized movement and cells with slow, unpolarized movement. Such differentiated motion gives rise to efficient colony expansion and consumption of the bacterial substrate. From these insights, we construct a theoretical model that predicts how disturbances to amoeba growth rate and movement disrupt their predation efficiency. These disturbances correspond to distinct classes of bacterial defenses, which allows us to experimentally validate our predictions. All considered, our characterization of amoeba foraging identifies amoeba mobility, and not amoeba growth, as the core determinant of predation efficiency and a key target for bacterial defense systems.

Minimal impacts on the wheat microbiome when Trichoderma gamsii T6085 is applied as a biocontrol agent to manage fusarium head blight disease.

Fusarium head blight (FHB) is a major fungal disease that causes severe yield and quality loss in wheat. Biological control can be integrated with other management strategies to control FHB. For this purpose, Trichoderma gamsii strain T6085 is a potential biocontrol agent to limit the infection of F. graminearum and F. culmorum in wheat. However, the possible impacts of T. gamsii T6085 on the broader microbiome associated with the wheat plant are not currently understood. Therefore, we identified bacteria and fungi associated with different wheat tissues, including assessment of their relative abundances and dynamics in response to the application of T6085 and over time, using amplicon sequencing. Residues of the prior year's wheat crop and the current year's wheat spikes were collected at multiple time points, and kernel samples were collected at harvest. DNA was extracted from the collected wheat tissues, and amplicon sequencing was performed to profile microbiomes using 16S v4 rRNA amplicons for bacteria and ITS2 amplicons for fungi. Quantitative PCR was performed to evaluate the absolute abundances of F. graminearum and T. gamsii in different wheat tissues. Disease progression was tracked visually during the growing season, revealing that FHB severity and incidence were significantly reduced when T6085 was applied to wheat spikes at anthesis. However, treatment with T6085 did not lessen the F. graminearum abundance in wheat spikes or kernels. There were substantial changes in F. graminearum abundance over time; in crop residue, pathogen abundance was highest at the initial time point and declined over time, while in wheat spikes, pathogen abundance increased significantly over time. The predominant bacterial taxa in wheat spikes and kernels were Pseudomonas, Enterobacter, and Pantoea, while Alternaria and Fusarium were the dominant fungal groups. Although the microbiome structure changed substantially over time, there were no community-scale rearrangements due to the T6085 treatment. The work suggests several other taxa that could be explored as potential biocontrol agents to integrate with T6085 treatment. However, the timing and the type of T6085 application need to be improved to give more advantages for T6085 to colonize and reduce the F. graminearum inoculum in the field.

Achievements, Developments and Future Challenges in the Field of Bioherbicides for Weed Control: A Global Review.

The intrusion of weeds into fertile areas has resulted in significant global economic and environmental impacts on agricultural production systems and native ecosystems, hence without ongoing and repeated management actions, the maintenance or restoration of these systems will become increasingly challenging. The establishment of herbicide resistance in many species and unwanted pollution caused by synthetic herbicides has ushered in the need for alternative, eco-friendly sustainable management strategies, such as the use of bioherbicides. Of the array of bioherbicides currently available, the most successful products appear to be sourced from fungi (mycoherbicides), with at least 16 products being developed for commercial use globally. Over the last few decades, bioherbicides sourced from bacteria and plant extracts (such as allelochemicals and essential oils), together with viruses, have also shown marked success in controlling various weeds. Despite this encouraging trend, ongoing research is still required for these compounds to be economically viable and successful in the long term. It is apparent that more focused research is required for (i) the improvement of the commercialisation processes, including the cost-effectiveness and scale of production of these materials; (ii) the discovery of new production sources, such as bacteria, fungi, plants or viruses and (iii) the understanding of the environmental influence on the efficacy of these compounds, such as atmospheric CO2, humidity, soil water stress, temperature and UV radiation.

A PDE Model for Protocell Evolution and the Origin of Chromosomes via Multilevel Selection.

The evolution of complex cellular life involved two major transitions: the encapsulation of self-replicating genetic entities into cellular units and the aggregation of individual genes into a collectively replicating genome. In this paper, we formulate a minimal model of the evolution of proto-chromosomes within protocells. We model a simple protocell composed of two types of genes: a "fast gene" with an advantage for gene-level self-replication and a "slow gene" that replicates more slowly at the gene level, but which confers an advantage for protocell-level reproduction. Protocell-level replication capacity depends on cellular composition of fast and slow genes. We use a partial differential equation to describe how the composition of genes within protocells evolves over time under within-cell and between-cell competition, considering an infinite population of protocells that each contain infinitely many genes. We find that the gene-level advantage of fast replicators casts a long shadow on the multilevel dynamics of protocell evolution: no level of between-protocell competition can produce coexistence of the fast and slow replicators when the two genes are equally needed for protocell-level reproduction. By introducing a "dimer replicator" consisting of a linked pair of the slow and fast genes, we show analytically that coexistence between the two genes can be promoted in pairwise multilevel competition between fast and dimer replicators, and provide numerical evidence for coexistence in trimorphic competition between fast, slow, and dimer replicators. Our results suggest that dimerization, or the formation of a simple chromosome-like dimer replicator, can help to overcome the shadow of lower-level selection and work in concert with deterministic multilevel selection in protocells featuring high gene copy number to allow for the coexistence of two genes that are complementary at the protocell level but compete at the level of individual gene-level replication. These results for the PDE model complement existing results on the benefits of dimerization in the case of low genetic copy number, for which it has been shown that genetic linkage can help to overcome the stochastic loss of necessary genetic templates.

Tissue-specific mRNA profiling of the Brassica napus-Sclerotinia sclerotiorum interaction uncovers novel regulators of plant immunity.

White mold is caused by the fungal pathogen Sclerotinia sclerotiorum and leads to rapid and significant loss in plant yield. Among its many brassicaceous hosts, including Brassica napus (canola) and Arabidopsis, the response of individual tissue layers directly at the site of infection has yet to be explored. Using laser microdissection coupled with RNA sequencing, we profiled the epidermis, mesophyll, and vascular leaf tissue layers of B. napus in response to S. sclerotiorum. High-throughput tissue-specific mRNA sequencing increased the total number of detected transcripts compared with whole-leaf assessments and provided novel insight into the conserved and specific roles of ontogenetically distinct leaf tissue layers in response to infection. When subjected to pathogen infection, the epidermis, mesophyll, and vasculature activate both specific and shared gene sets. Putative defense genes identified through transcription factor network analysis were then screened for susceptibility against necrotrophic, hemi-biotrophic, and biotrophic pathogens. Arabidopsis deficient in PR5-like RECEPTOR KINASE (PR5K) mRNA levels were universally susceptible to all pathogens tested and were further characterized to identify putative interacting partners involved in the PR5K signaling pathway. Together, these data provide insight into the complexity of the plant defense response directly at the site of infection.

Activation of NLR-Mediated Autoimmunity in Arabidopsis Early in Short Days 4 Mutant.

From a reverse genetic screen using CRISPR/Cas9 gene editing tool, we unintentionally identified an autoimmune mutant. Map-based cloning and whole-genome sequencing revealed that it contains a deletion in SMALL UBIQUITIN-RELATED MODIFIER (SUMO) protease encoding gene EARLY IN SHORT DAYS 4 (ESD4). Previous studies reported that esd4 mutants accumulate elevated levels of plant defense hormone salicylic acid (SA). However, upregulated PATHOGENESIS-RELATED GENE 1 (PR1) expression in esd4 only partly relies on SA level. In this study, we show that plant metabolite N-hydroxypipecolic acid (NHP) biosynthetic genes are upregulated in esd4, and NHP biosynthesis mutant flavin-dependent-monooxygenase 1 (fmo1) partially suppresses the autoimmune phenotypes of esd4, suggestive of a requirement of NHP signaling for the autoimmunity in esd4. As activation of nucleotide-binding leucine-rich repeat immune receptors (NLRs) are associates with the biosynthesis of SA and NHP and lipase-like protein ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) is a key component downstream of many NLRs, we examined the relationship between EDS1 and ESD4 by analyzing the eds1 esd4 double mutant. We found that eds1 largely suppresses esd4 autoimmunity and blocks the elevated expressions of SA and NHP biosynthesis-related genes in esd4. Overall, our study provides evidence supporting the hypothesis that SUMO protease ESD4 likely targets a yet to be identified guardee of NLR by removing its SUMO modification to avoid recognition by the cognate NLR. Loss of ESD4 results in activation of NLR-mediated autoimmunity.

A Synergistic Combination of DHA, Luteolin, and Urolithin A Against Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder and the most common form of dementia worldwide. The classical AD brain is characterized by extracellular deposition of amyloid-ß (Aß) protein aggregates as senile plaques and intracellular neurofibrillary tangles (NFTs), composed of hyper-phosphorylated forms of the microtubule-associated protein Tau. There has been limited success in clinical trials for some proposed therapies for AD, so attention has been drawn toward using alternative approaches, including prevention strategies. As a result, nutraceuticals have become attractive compounds for their potential neuroprotective capabilities. The objective of the present study was to derive a synergistic nutraceutical combination in vitro that may act as a potential preventative therapy for AD. The compounds of interest were docosahexaenoic acid (DHA), luteolin (LUT), and urolithin A (UA). The cell viability and cytotoxicity assays MTS and LDH were used to evaluate the compounds individually and in two-compound combinations, for their ability to inhibit Aß1-42-induced toxicity in human neuroblastoma BE(2)-M17 cells. The LDH-derived% protection values were used in the program CompuSyn v.1.0 to calculate the combination index (CI) of the two-compound combinations. The software-predicted potentially synergistic (CI < 1) two-compound combinations were validated using CellTiter Glo assay. Finally, a three-compound combination was predicted (D5L5U5) and shown to be the most effective at inhibiting Aß1-42-induced toxicity. The synergistic combination, D5L5U5 warrants further research for its mechanism of action; however, it can serve as a basis to develop an advanced functional food for the prevention or co-treatment of AD.

Antiviral Potential of Selected Medicinal Herbs and Their Isolated Natural Products.

Viruses are responsible for a variety of human pathogenesis. Owing to the enhancement of the world population, global travel, and rapid urbanization, and infectious outbreaks, a critical threat has been generated to public health, as preventive vaccines and antiviral therapy are not available. Herbal medicines and refined natural products have resources for the development of novel antiviral drugs. These natural agents have shed light on preventive vaccine development and antiviral therapies. This review intends to discuss the antiviral activities of plant extracts and some isolated plant natural products based on mainly preclinical (in vitro and in vivo) studies. Twenty medicinal herbs were selected for the discussion, and those are commonly recognized antiviral medicinal plants in Ayurveda (Zingiber officinale, Caesalpinia bonducella, Allium sativum, Glycyrrhiza glabra, Ferula assafoetida, Gymnema sylvestre, Gossypium herbaceum, Phyllanthus niruri, Trachyspermum ammi, Withania somnifera, Andrographis paniculata, Centella asiatica, Curcuma longa, Woodfordia fruticose, Phyllanthus emblica, Terminalia chebula, Tamarindus indica, Terminalia arjuna, Azadirachta indica, and Ficus religiosa). However, many viruses remain without successful immunization and only a few antiviral drugs have been approved for clinical use. Hence, the development of novel antiviral drugs is much significant and natural products are excellent sources for such drug developments. In this review, we summarize the antiviral actions of selected plant extracts and some isolated natural products of the medicinal herbs.

Potential of Sorghum Polyphenols to Prevent and Treat Alzheimer's Disease: A Review Article.

Alzheimer's disease (AD) is characterized by the excessive deposition of extracellular amyloid-beta peptide (Aß) and the build-up of intracellular neurofibrillary tangles containing hyperphosphorylated tau proteins. This leads to neuronal damage, cell death and consequently results in memory and learning impairments leading to dementia. Although the exact cause of AD is not yet clear, numerous studies indicate that oxidative stress, inflammation, and mitochondrial dysfunction significantly contribute to its onset and progression. There is no effective therapeutic approach to stop the progression of AD and its associated symptoms. Thus, early intervention, preferably, pre-clinically when the brain is not significantly affected, is a better option for effective treatment. Natural polyphenols (PP) target multiple AD-related pathways such as protecting the brain from Aß and tau neurotoxicity, ameliorating oxidative damage and mitochondrial dysfunction. Among natural products, the cereal crop sorghum has some unique features. It is one of the major global grain crops but in the developed world, it is primarily used as feed for farm animals. A broad range of PP, including phenolic acids, flavonoids, and condensed tannins are present in sorghum grain including some classes such as proanthocyanidins that are rarely found in others plants. Pigmented varieties of sorghum have the highest polyphenolic content and antioxidant activity which potentially makes their consumption beneficial for human health through different pathways such as oxidative stress reduction and thus the prevention and treatment of neurodegenerative diseases. This review summarizes the potential of sorghum PP to beneficially affect the neuropathology of AD.

Traditional Chinese Mind and Body Exercises for Neck Pain: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Neck pain is common and can have a significant impact on patients' physical functionality, mobility, and quality of life (QOL). In clinical practice, traditional Chinese mind and body exercise (TCMBE) is a combination of different types of exercise based on traditional Chinese medicine, including qigong, tai chi, the 12-words-for-life-nurturing exercise, and so on, and many studies have found that it is safe and effective at helping patients with neck pain. OBJECTIVE: The aim of this study was to investigate the effectiveness of TCMBE on pain intensity, functional mobility, and QOL in individuals with neck pain. METHODS: The PubMed, MEDLINE, PEDro, and Embase databases were systematically searched for relevant studies. Randomized controlled trials reporting the effects of TCMBE on pain intensity, functional mobility, and QOL in individuals with neck pain were included. Screening, data extraction, and literature quality assessments were performed independently by two reviewers. RevMan5.4 software was used for data analysis. RESULTS: Six studies with 716 participants met the inclusion criteria. Compared with the control groups, TCMBE had no therapeutic advantage in improving pain intensity (visual analogue scale: mean difference (MD) = 1.8, 95% confidence interval (CI): -7.70 to 11.46, and P = 0.70); functional mobility (neck disability index: MD = 0.15, 95% CI: -6.37 to 6.66, and P = 0.96; neck pain and disability scale: MD = 1.31, 95% CI: -4.10 to 6.71, and P = 0.64); or 36-item short-form health survey (SF-36) scores for physical function (MD = 5.58, 95% CI: -8.03 to 19.18, and P = 0.42), general health (MD = 1.87, 95% CI: -4.99 to 8.72, and P = 0.59), body pain (MD = 2.26, 95% CI: -3.80 to 8.32, and P = 0.46), vitality (MD = 6.24, 95% CI: -1.49 to 13.98, and P = 0.11), social function (MD = 8.06, 95% CI: -4.85 to 20.98, and P = 0.22), role physical (MD = -1.46, 95% CI: -8.54 to 5.62, and P = 0.69), or role emotional (MD = 6.5, 95% CI: -3.45 to 16.45, and P = 0.2). However, TCMBE was less effective at improving mental health results based on the SF-36 survey (MD = 3.37, 95% CI: 0.5 to 6.24, and P = 0.02). CONCLUSIONS: Based on the meta-analysis, there is insufficient evidence to support the clinical use of TCMBE in improving pain intensity and enhancing functional mobility and QOL in individuals with neck pain.

Naturally Occurring Fusarium Species and Mycotoxins in Oat Grains from Manitoba, Canada.

Fusarium head blight (FHB) can lead to dramatic yield losses and mycotoxin contamination in small grain cereals in Canada. To assess the extent and severity of FHB in oat, samples collected from 168 commercial oat fields in the province of Manitoba, Canada, during 2016-2018 were analyzed for the occurrence of Fusarium head blight and associated mycotoxins. Through morphological and molecular analysis, F. poae was found to be the predominant Fusarium species affecting oat, followed by F. graminearum, F. sporotrichioides, F. avenaceum, and F. culmorum. Deoxynivalenol (DON) and nivalenol (NIV), type B trichothecenes, were the two most abundant Fusarium mycotoxins detected in oat. Beauvericin (BEA) was also frequently detected, though at lower concentrations. Close clustering of F. poae and NIV/BEA, F. graminearum and DON, and F. sporotrichioides and HT2/T2 (type A trichothecenes) was detected in the principal component analysis. Sampling location and crop rotation significantly impacted the concentrations of Fusarium mycotoxins in oat. A phylogenetic analysis of 95 F. poae strains from Manitoba was conducted using the concatenated nucleotide sequences of Tef-1α, Tri1, and Tri8 genes. The results indicated that all F. poae strains belong to a monophyletic lineage. Four subgroups of F. poae strains were identified; however, no correlations were observed between the grouping of F. poae strains and sample locations/crop rotations.