From soil to plant: strengthening carrot defenses against Meloidogyne incognita with vermicompost and arbuscular mycorrhizal fungi biofertilizers.

Introduction: Sustainable agricultural practices for controlling crop pests are urgently needed to reduce the reliance on chemical pesticides, which have long-term detrimental effects on ecosystems. In this study, we assessed the effectiveness of arbuscular mycorrhizal fungi (AMF) and vermicompost (Vc) supplementation, alone and in combination, in mitigating the negative impacts of Meloidogyne incognita infestation on carrot (Daucus carota L.) growth, development, and physiology. Methods: We measured different plant growth parameters such as plant height and biomass accumulation, several plant physiological parameters such as the levels of photosynthetic pigments, phenolics, and the activity of defense enzymes such as peroxidases and polyphenol oxidases, and evaluated the severity of Meloidogyne incognita nematode infestation on plants treated or not treated with vermicompost (Vc) and/or arbuscular mycorrhizal fungi (AMF). Results: Our findings show that M. incognita significantly affects plant growth, biomass accumulation, and photosynthetic pigment and carotenoid content. The incorporation of Vc and AMF into the soil, either individually or in combination, significantly alleviates the negative effects of nematode infestation on carrot plants. This was accompanied by the induction of phenolic compounds and defense enzymes such as peroxidases (+15.65%) and polyphenol oxidases (29.78%), and by a reduction in the severity of nematode infestation on Vc and AMF-treated plants compared to nematode-infested plants. Principal component analysis (PCA) shows significant correlations between various of the studied parameters. In particular, we observed negative correlations between the application of AMF and Vc alone and in combination and disease severity, and positive correlations between plant growth, photosynthetic pigments phenol content, and activity of defense enzymes. Discussion: Our study highlights the relevance of cultural practices and beneficial microorganisms for the sustainable and environmentally friendly management of agricultural pests.

Novel mannich-based derivative of 2-mercaptobenzimidazole (AK7): a new candidate for the treatment of inflammatory arthritis owing to its NF-κB1 inhibitory potential.

This study investigated the anti-arthritic potential of novel mannich-based derivatives of 2-mercaptobenzimidazole (AK7 and AK9) in rats. The compounds were characterized by NMR and FTIR spectroscopies and their acute anti-inflammatory effects were measured by carrageenan (CRG)-induced paw edema model. The most potent doses of AK7 and AK9 were subsequently evaluated in the complete Freund's adjuvant (CFA)-induced inflammatory arthritis model. AK7 and AK9 inhibited CRG-induced inflammation in a dose-dependent fashion and a similar reduction in CFA-induced paw inflammation was observed. Moreover, X-ray and histopathological analyses of AK7-treated animals displayed normal joint structure whereas AK9, despite of its anti-inflammatory effects, failed to protect against cartilage destruction. Interestingly, biochemical analysis revealed a better safety profile for AK7 than for AK9 and methotrexate. Both compounds suppressed mRNA levels of pro-inflammatory mediators (IRAK1, NF-κB1, TNF-α, IL1B) while only AK7 reduced the transcript levels of interstitial collagenase (MMP1). Molecular docking analysis of AK7 and AK9 with TNF-α and MMP1 also supported the experimental data. These findings clearly highlight the beneficial effects of AK7 in the prevention and/or treatment of inflammatory arthritis.

Which type of mind-body exercise is most effective in improving functional performance and quality of life in patients with Parkinson's disease? A systematic review with network meta-analysis.

BACKGROUND: Several studies have investigated the effect of mind-body exercise (MBE) on functional performance and health-related quality of life (HRQoL) in Parkinson's disease (PD), but it is still very difficult for clinicians to make informed decision on the best mind-body exercise for PD. PURPOSE: We analyzed the relative efficacy of MBE (yoga, Tai-Chi, Pilates, Qigong, and dance) in improving functional performance and HRQoL in patients with PD. METHODS: A systematic review of randomized controlled trials (RCTs) was performed using network meta-analysis (NMA), searching the following databases: Cochrane, Web of Science, and PubMed using specific keywords until December 28, 2021, assessing the effects of MBE on functional performance and HRQoL in patients with PD. RESULTS: This review included 60 RCTs with 2037 participants. A ranking of MBE for modifying various aspects of functional performance and HRQoL was achieved. Pairwise NMA showed Pilates to be the most effective in improving functional mobility (MD: - 3.81; 95% CI (- 1.55, - 6.07) and balance performance (SMD: 2.83; 95% CI (1.87, 3.78). Yoga (MD: - 5.95; 95% CI (- 8.73, - 3.16) and dance (MD: - 5.87; 95% CI (- 8.73, - 3.01) to be the most effective in improving motor function, whereas Qigong (MD: 0.32; 95% CI (0.00, 0.64) was most effective in improving gait speed. Considering HRQoL, dance was found to be the most effective (SMD: - 0.36; 95% CI (- 0.70, -0.01). CONCLUSION: MBE should be considered an effective strategy for improving functional performance and HRQoL in patients with PD. The most effective MBE intervention varied with the functional performance domain. Dance was an effective exercise for improving HRQoL among people with PD. PROSPERO REGISTRATION ID: CRD42022301030.

Novel acetamide derivatives of 2-aminobenzimidazole prevent inflammatory arthritis in rats via suppression of pro-inflammatory mediators.

Benzimidazole ring system is an important pharmacophore with diverse pharmacological activities. In this study, we explored the anti-arthritic effects of newly synthesized acetamide derivatives of 2-aminobenzimidazole (N1 and N2) in rats. FTIR and NMR spectroscopies were used to characterize these compounds. Carrageenan (CRG) induced paw edema model was used to test the acute anti-inflammatory activity of various doses (10, 20 and 30 mg/kg) of N1 and N2 compounds. Based on acute anti-inflammatory effects, the most potent dose of each compound was selected and investigated in complete freund's adjuvant (CFA) induced inflammatory arthritis (RA) model (n = 4 in each group). Histopathological, hematological, radiographic, and RT-qPCR analyses were performed to assess the progression or resolution of inflammatory arthritis. The tested compounds produced a dose-dependent anti-inflammatory activity against CRG induced paw inflammation and similarly reduced edema in CFA induced inflammatory arthritis model. Histopathological and X-ray analyses of ankle joints revealed minimal inflammation and normal joint structures in N1 and N2 treated groups. The tested compounds also reduced the levels of autoantibodies and restored hematological parameters. Interestingly, the tested compounds did not elevate aspartate aminotransferase and alanine transaminase levels and displayed a better safety profile than methotrexate. N1 and N2 compounds also attenuated the transcript levels of IRAK1, NF-kB1, TNF-α, IL-1ß, IL17 and MMP1. In addition, N1 displayed a greater inhibition of mRNA levels of COX1, COX2, mPGES1 and PTGDS as compared to N2. Our findings demonstrate that N1 and N2 compounds possess strong anti-arthritic activity which can be attributed to the suppression of pro-inflammatory mediators.

Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders.

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer-both in vivo and in vitro clinical trials-has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

Biogenic Nanoparticle‒Chitosan Conjugates with Antimicrobial, Antibiofilm, and Anticancer Potentialities: Development and Characterization.

In the 21st century, with ever-increasing consciousness and social awareness, researchers must tackle the microbial infections that pose a major threat to human safety. For many reasons, the emergence/re-emergence of threatening pathogens has increased and poses a serious challenge to health care services. Considering the changing dynamics of 21st-century materials with medical potentialities, the integration of bioactive agents into materials to engineer antibacterial matrices has received limited attention so far. Thus, antimicrobial active conjugates are considered potential candidates to eradicate infections and reduce microbial contaminations in healthcare facilities. In this context, eco-friendly and novel conjugates with antimicrobial, antibiofilm, and anticancer potentialities were developed using biogenic silver nanoparticles (AgNPs) from Convolvulus arvensis (C. arvensis) extract and chitosan (CHI). A range of instrumental and imaging tools, i.e., UV-Vis and FTIR spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDX), and X-ray diffraction (XRD), were employed to characterize the freshly extracted C. arvensis AgNPs. Biogenic AgNPs obtained after a 24-h reaction period were used to engineer CHI-based conjugates and designated as CHI‒AgNPs1 to CHI‒AgNPs5, subject to the C. arvensis AgNPs concentration. After the stipulated loading period, 92% loading efficiency (LE) was recorded for a CHI‒AgNPs3 conjugate. Gram+ and Gram- bacterial isolates, i.e., Staphylococcus aureus, and Escherichia coli, were used to test the antibacterial activities of newly developed CHI‒AgNPs conjugates. In comparison to the control sample with bacterial cell count 1.5 × 108 CFU/mL, a notable reduction in the log values was recorded for the CHI‒AgNPs3 conjugate. The antibiofilm potential of CHI‒AgNPs conjugates was tested against Pseudomonas aeruginosa. Moreover, the CHI‒AgNPs3 conjugate also showed substantial cytotoxicity against the MCF-7 (breast cancer) cell line. In summary, the newly engineered CHI‒AgNPs conjugates with antibacterial, antibiofilm, and anticancer potentialities are potential candidate materials for biomedical applications.

Intercalating Electron Dyes for TEM Visualization of DNA at the Single-Molecule Level.

Staining compounds containing heavy elements (electron dyes) can facilitate the visualization of DNA and related biomolecules by using TEM. However, research into the synthesis and utilization of alternative electron dyes has been limited. Here, we report the synthesis of a novel DNA intercalator molecule, bis-acridine uranyl (BAU). NMR spectroscopy and MS confirmed the validity of the synthetic strategy and gel electrophoresis verified the binding of BAU to DNA. For TEM imaging of DNA, two-dimensional DNA origami nanostructures were used as a robust microscopy test object. By using scanning transmission electron microscopy (STEM) imaging, which is favored over conventional wide-field TEM for improved contrast, and therefore, quantitative image analysis, it is found that the synthesized BAU intercalator can render DNA visible, even at the single-molecule scale. For comparison, other staining compounds with a purported affinity towards DNA, such as dichloroplatinum, cisplatin, osmium tetroxide, and uranyl acetate, have been evaluated. The STEM contrast is discussed in terms of the DNA-dye association constants, number of dye molecules bound per base pair, and the electron-scattering capacity of the metal-containing ligands. These findings pave the way for the future development of electron dyes with specific DNA-binding motifs for high-resolution TEM imaging.

Herbal Immunomodulators - A Remedial Panacea for Designing and Developing Effective Drugs and Medicines: Current Scenario and Future Prospects.

BACKGROUND: Constant exposure to various stressors, such as immune pressure, rapidly increasing population, deleterious changes in the ecosystem, climate change, infection with emerging and re-emerging pathogens, and fast-paced lifestyle, is a critical factor in the globally increasing incidences of immunocompromising health conditions, as well as stress. Synthetic chemotherapeutic agents, which are widely available in the commercial market, may be highly efficacious, but most are immunosuppressive and exert many side effects. METHODS: Herein, we comprehensively reviewed current literature from various scientific databases such as Bentham Science, PubMed, Scopus, Elsevier, Springer, etc. The inclusion/exclusion criteria based on literature with high importance was adopted to analyze and compile salient information from the authentic bibliographic sources. RESULTS: Undoubtedly, the pivotal characteristics of immunostimulants and immunomodulators in the maintenance of the health and productivity of humans, as well as animals, cannot be overlooked. Numerous herbs used in ethnoveterinary medicine can be successfully employed as adjuvant rehabilitators to negate the deleterious effects of chemotherapeutics. The sources of these medicinal remedies are part of long traditions in different regions of the world, such as Indian Ayurveda and Traditional Chinese Medicine, which have been developed through empirical experience. Traditional medicine employs a holistic approach to the prevention of disease, and traditional herbal medicines are a source of many components with a high therapeutic value that are used in modern allopathic medicine. Globally, many studies have been conducted on these herbs and have revealed unique active constituents that activate the innate immune system through the stimulation of macrophages and lymphocytes, and modulation of the cytokine profile, which leads to a state of alertness with a subsequent reduction in the incidence of infection. Immunomodulatory constituents with herbal origins are termed as phytochemicals, including flavonoids, glycosides, polysaccharides, terpenoids, essential oils, various bitters, and alkaloids; all these compounds exert vital, multidimensional effects. Efforts have focused on screening plant preparations to identify adjuvant immune properties; furthermore, several potent phytol adjuvants have been experimentally proven to downregulate inflammatory reactions in addition to enhance specific adaptive responses to vaccines. CONCLUSIONS: In summary, this review summarizes the current status and future prospects regarding the immunomodulatory potential of various herbs and plants and their promising utility for designing and developing effective drugs and medicines in safeguarding the health of humans, animals, and poultry.

Anti-avian influenza virus H9N2 activity of aqueous extracts of Zingiber officinalis (Ginger) and Allium sativum (Garlic) in chick embryos.

In the present study, anti-Avian influenza virus H9N2 activity of aqueous extracts (5, 10, 15, 20, 25%) of Zingiber officinalis and Allium sativum was evaluated. Embryo-toxicity was evaluated by histopathological scoring of Chorio-allantoic membrane of chick embryos. Cytotoxicity of extracts was determined by MTT assay on Vero cells. Aqueous extract of ginger had antiviral activity at 10, 15, 20 and 25% while garlic had activity at 15, 20 and 25%. Histopathological scoring of chorio-allantoic membrane for aqueous extracts (5, 10, 15, 20, 25%) of ginger (0.66±0.57, 1.33±0.57, 1.66±0.57, 2.66±0.57, 3.66±0.57, respectively) and garlic (1.00±0.00, 1.33±0.57, 2.00±0.00, 2.33±0.57, 3.66±0.57, respectively) was concentration dependant. MTT assay revealed cytotoxicity of both plants was also concentration dependent. Extracts of ginger (5, 10, 15, 20, 25%) had lower cytotoxicity (71, 59, 28, 22, 0 % cell survival, respectively) as compared to garlic (61, 36. 20, 11, 3% cell survival, respectively). Overall results revealed that concentration of aqueous extract of ginger (10%), showing antiviral activity against H9N2, was less toxic to vero cells (> 50% cell survival). It is insinuated that ginger may have anti- Avian influenza virus H9N2 potential and its active compounds needs further investigations.

The genus Pluchea: phytochemistry, traditional uses, and biological activities.

In this review, literature data on phytochemical and biological investigations on the genus Pluchea are compiled. Pluchea is a genus of flowering plants in the Asteraceae family and comprises ca. 80 species distributed mainly in Northern and Southern America, Africa, Asia, and Australia. Sesquiterpenoids and flavonoids are the main constituents of this genus. Compounds isolated from plants of the Pluchea genus display a variety of biological properties, viz., anticancer, antileishmanial, immunosuppressive, antioxidant, anti-acetylcholinesterase, antimicrobial, trypanocidal, hepatoprotective, cytotoxic, larvicidal, anti-ulcer, anti-inflammatory, and antinociceptive activities.

Clickable tyrosine binding bifunctional linkers for preparation of DNA-protein conjugates.

We have prepared bifunctional linkers containing clickable functional groups that enable preparation of protein-DNA conjugates through binding onto tyrosine residues. Mild conjugation strategy was demonstrated using two proteins, streptavidin(STV) and myoglobin (Mb) and it resulted in conjugates with preserved functionality of both the proteins and DNA strands. Furthermore, we show that protein-DNA conjugates can be successfully immobilized onto solid surface containing complementary DNA strands and the enzymatic activity of Mb-DNA conjugates is even higher than that of corresponding conjugates prepared through Lys binding.

Kenganthranol F, a new anthranol from Psorospermum aurantiacum.

A new anthranol, kenganthranol F, was isolated from the ethyl acetate extracts of the seeds and the whole plant of the Cameroonian plant Psorospermum aurantiacum (Hypericaceae), together with fifteen known compounds viz., ferruginin B, vismin, vismion D, haronginanthrone, kenganthraquinone, kenganthranol B and kenganthranol E isolated from the fruits and 3-geranyloxyemodinanthrone, 2-geranylemodin, bianthrone A1, vismione D, 1,8-dihydroxy-3-geranyloxy-6-methylanthraquinone, vismione M, vismiaquinone, vismiaquinone C being isolated from the whole plant. The structure of the new isomer of kenganthranol F was determined to be 1,8,10-trihydroxy-3,4-[2,2-dimethyldihydropyrano]-6-methyl-2,5-bis-(3,3-dimethylallyl)-anthrone.

Melicilamide A: a new ceramide from Milicia excelsa.

This article deals with a phytochemical investigation of Melicia excelsa from which melicilamide A (1), a new ceramide has been isolated. Its structure was determined by comprehensive analyses of its (1)H- and (13)C-NMR, COSY, HMQC and HMBC spectroscopic, EI-MS and ESI-MS data. The remaining one known compound was identified as ß-sitosterol glucopyranoside.

Pyrenocines J-M: four new pyrenocines from the endophytic fungus, Phomopsis sp.

Four new pyrenocines, named pyrenocines J-M (1-4), were isolated from an endophytic fungus, Phomopsis sp, by a bioassay-guided method. The structures of the new compound have been assigned from ¹H and ¹³C NMR spectra, DEPT, and by 2D COSY, HMQC, and HMBC experiments. Preliminary studied showed that compounds 1, 2 and 4 showed good antifungal, antibacterial, and algicidal properties, while compound 3 had good antibacterial and algicidal properties.

Two new alkylanacardic acids, ozorcardic A and B, from Ozoroa pulcherrima.

Two new alkylanacardic acids, ozorcardic A (1) and B (2), along with the known and related metabolite anacardic acid (3), were isolated from Ozoroa pulcherrima. The structures of the new compounds were elucidated by detailed spectroscopic and spectrometric analysis.

Bioactive aromatic derivatives from endophytic fungus, Cytospora sp.

Two new benzyl gamma-butyrolactone analogues, (R)-5-((S)-hydroxy(phenyl)-methyl)dihydrofuran-2(3H)-one (1) and its 6-acetate (2), and a new naphthalenone derivative (8), together with eight additional known aromatic derivatives, (S)-5-((S)-hydroxy(phenyl)-methyl)dihydrofuran-2(3H)-one (3), (S)-5-benzyl-dihydrofuran-2(3H)-one (4), 5-phenyl-4-oxopentanoic acid (5), gamma-oxo-benzenepentanoic acid methyl ester (6), 3-(2,5-dihydro-4-hydroxy-5-oxo-3-phenyl-2-furyl)propionic acid (7), (3R)-5-methylmellein (9), integracins A (10) and B (11) were isolated from Cytospora sp., an endophytic fungus isolated from Ilex canariensis from Gomera. The structures of these compounds were elucidated by detailed spectroscopic analysis, comparison with reported data, and chemical interconversion. The absolute configurations of the new compounds (1, 2, 8) were established on the basis of optical rotation or CD spectra analysis. Preliminary studies showed antimicrobial activity of these compounds against the fungi Microbotryum violaceum, Botrytis cinerea and Septoria tritici, the alga Chlorella fusca, and the bacterium Bacillus megaterium.

Antimicrobial chemical constituents from the endophytic fungus Phomopsis sp. from Notobasis syriaca.

Phomosine K (1), a new phomosine derivative, has been isolated from Phomopsis sp., in addition to six known compounds: phomosine A (2), phenylalanine amide (3), 2-hydroxymethyl-4beta,5alpha,6beta-trihydroxycyclohex-2-en (4), (-)-phyllostine (5), (+)-epiepoxydon (6), and (+)-epoxydon monoacetate (7). Preliminary studies showed that compound 1 had strong antibacterial activity, while compounds 4-7 showed good antifungal, antibacterial, and algicidal properties, except compounds 4 and 6, which lacked antifungal activity.

Phomosines H-J, novel highly substituted biaryl ethers, isolated from the endophytic fungus Phomopsis sp. from Ligustrum vulgare.

From the endophytic fungus Phomosis sp., four known phomosines A-D (1-4) and three new phomosines H-J (5-7) have been isolated. The structures of the new compounds were determined on the basis of their spectroscopic data analysis (1H, 13C, 1H-1H COSY, HMQC, and HMBC NMR, as well as mass spectrometry). The structures of phomosine H (5) and J (7) were also confirmed by semisynthesis from phomosine A (1). The remaining four known compounds [phomosines A-D (1-4)] were identified by comparing their spectroscopic data with those reported in the literature. The four known metabolites were biologically active. Of the novel metabolites, only 6 was antifungal and antibacterial.

Hyloglyceride and hylodiglyceride: two new glyceride derivatives from Hylodendron gabunensis.

Phytochemical investigation of Hylodendron gabunensis resulted in the isolation of two new glyceride derivatives, hyloglyceride (1) and hylodiglyceride (2). The structures of the two new compounds were determined by comprehensive analysis of their 1D and 2D NMR spectroscopic, and HREIMS data. One known compound was also isolated and identified as beta-sitosterol.

Modulation of the K(v)4.3 channel by syntaxin 1A.

The SNARE protein syntaxin 1A (Syn1A) is known to inhibit delayed rectifier K(+) channels of the K(v)1 and K(v)2 families with heterogeneous effects on their gating properties. In this study, we explored whether Syn1A could directly modulate K(v)4.3, a rapidly inactivating K(v) channel with important roles in neuroendocrine cells and cardiac myocytes. Immunoprecipitation studies in HEK293 cells coexpressing Syn1A and K(v)4.3 revealed a direct interaction with increased trafficking to the plasma membrane without a change in channel synthesis. Paradoxically, Syn1A inhibited K(v)4.3 current density. In particular, Syn1A produced a left-shift in steady-state inactivation of K(v)4.3 without affecting either voltage dependence of activation or gating kinetics, a pattern distinct from other K(v) channels. Combined with our previous reports, our results further verify the notion that the mechanisms involved in Syn1A-K(v) interactions vary significantly between K(v) channels, thus providing a wide scope for Syn1A modulation of exocytosis and membrane excitability.