Characterization of structural, genotoxic, and immunological effects of methyl methanesulfonate (MMS) induced DNA modifications: Implications for inflammation-driven carcinogenesis.

Genotoxic DNA damaging agents are the choice of chemicals for studying DNA repair pathways and the associated genome instability. One such preferred laboratory chemical is methyl methanesulfonate (MMS). MMS, an SN2-type alkylating agent known for its ability to alkylate adenine and guanine bases, causes strand breakage. Exploring the outcomes of MMS interaction with DNA and the associated cytotoxicity will pave the way to decipher how the cell confronts methylation-associated stress. This study focuses on an in-depth understanding of the structural instability, induced antigenicity on the DNA molecule, cross-reactive anti-DNA antibodies, and cytotoxic potential of MMS in peripheral lymphocytes and cancer cell lines. The findings are decisive in identifying the hazardous nature of MMS to alter the intricacies of DNA and morphology of the cell. Structural alterations were assessed through UV-Vis, fluorescence, liquid chromatography, and mass spectroscopy (LCMS). The thermal instability of DNA was analyzed using duplex melting temperature profiles. Scanning and transmission electron microscopy revealed gross topographical and morphological changes. MMS-modified DNA exhibited increased antigenicity in animal subjects. MMS was quite toxic for the cancer cell lines (HCT116, A549, and HeLa). This research will offer insights into the potential role of MMS in inflammatory carcinogenesis and its progression.

Molecular pathways and therapeutic targets linked to triple-negative breast cancer (TNBC).

Cancer is a group of diseases characterized by uncontrolled cellular growth, abnormal morphology, and altered proliferation. Cancerous cells lose their ability to act as anchors, allowing them to spread throughout the body and infiltrate nearby cells, tissues, and organs. If these cells are not identified and treated promptly, they will likely spread. Around 70% of female breast cancers are caused by a mutation in the BRCA gene, specifically BRCA1. The absence of progesterone, oestrogen and HER2 receptors (human epidermal growth factor) distinguishes the TNBC subtype of breast cancer. There were approximately 6,85,000 deaths worldwide and 2.3 million new breast cancer cases in women in 2020. Breast cancer is the most common cancer globally, affecting 7.8 million people at the end of 2020. Compared to other cancer types, breast cancer causes more women to lose disability-adjusted life years (DALYs). Worldwide, women can develop breast cancer at any age after puberty, but rates increase with age. The maintenance of mammary stem cell stemness is disrupted in TNBC, governed by signalling cascades controlling healthy mammary gland growth and development. Interpreting these essential cascades may facilitate an in-depth understanding of TNBC cancer and the search for an appropriate therapeutic target. Its treatment remains challenging because it lacks specific receptors, which renders hormone therapy and medications ineffective. In addition to radiotherapy, numerous recognized chemotherapeutic medicines are available as inhibitors of signalling pathways, while others are currently undergoing clinical trials. This article summarizes the vital druggable targets, therapeutic approaches, and strategies associated with TNBC.

Effectiveness of stingless bee (Kelulut) honey versus conventional gel dressing in diabetic wound bed preparation: A randomized controlled trial.

Purpose: Kelulut honey contains trehalulose and has high antioxidant content, such as phenolic and flavonoid substances, which can promote wound healing. This study evaluated the effectiveness of Kelulut honey in diabetic wound healing compared to a commercially available conventional gel dressing (Intrasite gel). Methods: A prospective, randomized, single-blinded control trial was performed on eligible diabetic patients with full-thickness cavity wounds. Patients' demographics, size and site of wounds, and baseline routine blood investigations were recorded. The wounds were dressed every other day with Kelulut honey for the intervention group or gel for the control group. The wound size reduction and granulation tissue formation percentage were calculated every 6 days for 1 month. Results: Seventy-one patients were randomized. After 30 days of follow-up, 62 participants were available for analysis: 30 from the control group and 32 from the treatment group. The control group had increased granulation tissue at baseline and more wounds on the lower limb and posterior trunk. Both groups showed an increasing mean and median percentage of wound epithelialization and granulation tissue over time, with significantly higher values at every timepoint in the honey group (p < 0.05). However, repeated measures analysis of variance and analysis of covariance revealed no significant interaction effect between the different treatments and time, with F (2.02, 121.28) = 0.88, p = 0.417 and F (1.60, 93.95) = 0.79, p = 0.431, respectively. Conclusion: This study revealed that Kelulut honey was comparable to and as effective as the conventional gel in treating diabetic wounds in terms of promoting epithelialization and granulation tissue formation.

Non-Mixture Cure Model Estimation in Bladder Cancer Patients: A Novel Approach with Exponentiated Weibull Exponential Distribution.

OBJECTIVE: Cure models are frequently used in survival analysis to account for a cured fraction in the data. When there is a cure rate present, researchers often prefer cure models over parametric models to analyse the survival data. These models enable the ability to define the probability distribution of survival durations for patients who are at risk. Various distributions can be considered for the survival times, such as Exponentiated Weibull Exponential (EWE), Exponential Exponential (EE), Weibull and lognormal distribution. The objective of this research is to choose the most appropriate distribution that accurately represents the survival times of patients who have not been cured. This will be accomplished by comparing various non-mixture cure models that are based on the EWE distribution with its sub-distributions, and distributions distinct from those belonging to the EWE distribution family. MATERIAL AND METHODS: A sample of 85 patients diagnosed with superficial bladder tumours was selected to be used in fitting the non-mixture cure model. In order to estimate the parameters of the suggested model, which takes into account the presence of a cure rate, censored data, and covariates, we utilized the maximum likelihood estimation technique using R software version 3.5.7. RESULT: Upon conducting a comparison of various parametric models fitted to the data, both with and without considering the cure fraction and without incorporating any predictors, the EE distribution yields the lowest AIC, BIC, and HQIC values among all the distributions considered in this study, (1191.921/1198.502, 1201.692/1203.387, 1195.851/1200.467). Furthermore, when considering a non-mixture cure model utilizing the EE distribution along with covariates, an estimated ratio was obtained between the probabilities of being cured for placebo and thiotepa groups (and its 95% confidence intervals) were 0.76130 (0.13914, 6.81863). CONCLUSION: The findings of this study indicate that EE distribution is the optimal selection for determining the duration of survival in individuals diagnosed with bladder cancer.

Albumin from sera of rheumatoid arthritis patients share multiple biochemical, biophysical and immunological properties with in vitro generated glyco-nitro-oxidized-albumin.

The purpose of the present study is to explore the effects of endogenous stressors on structure and function of rheumatoid arthritis (RA) patients' albumin. In contrast to glycated-albumin or nitro-oxidized-albumin, high titre antibodies against glyco-nitro-oxidized-albumin were found in the sera of RA patients. Also, compared to the other two modified forms of albumin, glyco-nitro-oxidized-albumin showed highest percent inhibition. Albumin isolated from RA patients' sera displayed hyperchromicity and quenching of tyrosine and tryptophan fluorescence. Fluorescence spectroscopy studies also revealed the presence of dityrosine and advanced glycation end products in RA patient's albumin. RA patients' albumin showed weaker binding with 1-anilinonaphthalene-8-sulfonic acid dye. Secondary structure alterations were demonstrated by circular dichroism and Fourier transform infrared spectroscopy. Biochemical investigations revealed substantial decline in the availability of free side chains of amino acid residues; increased carbonyls and decreased sulfhydryls in RA patients' albumin. The functional impairment in RA patients' albumin was revealed by their low binding with bilirubin and cobalt. Liquid chromatography mass spectrometry analysis revealed the presence of Nε-(carboxymethyl) lysine and 3-nitrotyrosine in RA patients' albumin. The amyloidogenic aggregation of RA patients' albumin was confirmed by Congo red absorption and thioflavin-T fluorescence assays. The morphology of the aggregates was visualized under scanning and transmission electron microscope. From the above findings, we inferred that endogenous stress in RA patients have modified albumin and produce structural/functional abnormalities. Also, the presence of anti-glyco-nitro-oxidized-albumin antibodies along with other clinical features may be used as biomarker for the diagnosis and assessment of treatment responses in RA patients.Communicated by Ramaswamy H. Sarma.

Protective Mechanism Pathway of Swietenia macrophylla Extract Nanoparticles against Cardiac Cell Damage in Diabetic Rats.

Hyperglycemia causes cardiac cell damage through increasing ROS production during diabetic complications. The current study proves the antioxidant activity of Swietenia macrophylla (S. macrophylla) extract nanoparticles as a protector against streptozotocin (STZ)-induced cardiac cell damage. In this research, high-energy ball milling is used to create S. macrophylla extract nanoparticles. The active chemical compounds in the S. macrophylla extract nanoparticles were analyzed through phytochemical screening and GC-MS. Furthermore, we characterized the size of S. macrophylla extract nanoparticles with Dynamic Light Scattering (DLS). Forty male rats were divided randomly into five groups. In the control group, rats received aqua dest orally; in the diabetic group, rats were injected intraperitoneally with STZ; in the S. macrophylla group, rats were injected with STZ and orally given S. macrophylla extract nanoparticles. The results of phytochemical screening showed that S. macrophylla extract nanoparticles contain saponins, flavonoids, alkaloids, phenolics and tannins. Seven chemical compounds in S. macrophylla extract nanoparticles were identified using GC-MS, including phenol, piperidine, imidazole, hexadecene, heptadecanol, dihexylsulfide and heptanol. DLS showed that the S. macrophylla extract nanoparticles' size was 91.50 ± 23.06 nm. Injection with STZ significantly increased malondialdehyde (MDA) levels in cardiac tissue and creatine kinase-myocardial band (CK-MB) and lactate dehydrogenase (LDH) levels in serum. STZ also significantly reduced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and the level of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in cardiac tissue compared with the control group (p < 0.05). In contrast, the administration of S. macrophylla extract nanoparticles can prevent STZ-induced cardiac cell damage through decreasing the level of CK-MB and LDH in serum and the level of MDA in cardiac tissue. S. macrophylla extract nanoparticles also significantly increased Nrf2 expression as well as SOD and GPx levels in cardiac tissue. These effects are related to the prevention of cardiac histopathological alteration (degeneration and necrosis) in diabetic rats. These results suggest that S. macrophylla nanoparticles contain active compounds such as flavonoids, phenols, piperidine, imidazole and hexadecene and have strong antioxidant activity. These can act as a potential cardioprotective agent against STZ-induced cardiac cell damage due to its antioxidant properties.

Studies on the synergistic action of methylglyoxal and peroxynitrite on structure and function of human serum albumin.

Albumin, an important serum protein, is continuously exposed to various oxidizing/nitrating and glycating agents. Depending upon the nature/concentration of reactive species present, the protein may be glycated, oxidized/nitroxidized or glyco-nitro-oxidized. Peroxynitrite is a powerful nitroxidant and has been reported to damage a wide array of macromolecules. On the other hand, methylglyoxal is a very strong reactive dicarbonyl and a potent precursor for the formation of advanced glycation end products under pathological conditions. In certain pathological conditions albumin may be modified by peroxynitrite and methylglyoxal simultaneously. There is dearth of literature suggests that structural/conformational and functional alteration in albumin upon glycation and oxidation/nitroxidation, however the alterations produced by glyco-nitro-oxidation has not yet been explored. Therefore, in this study, simultaneous effect of glycation and nitroxidation on the structure and conformation, vis-a-vis function of albumin was explored. Glyco-nitro-oxidized albumin showed decreased free amino acid content together with decreased affinity of albumin towards cobalt. Molecular docking model and molecular dynamic simulations showed close interaction and formation of stable complexes between methylglyoxal, peroxynitrite and albumin. Formation of carboxymethyl lysine and 3-nitrotyrosine in glyco-nitro-oxidized albumin were confirmed by MALDI-TOF MS and UP-LC MS. Aggregate formation in glyco-nitro-oxidized albumin was visualized by transmission electron microscopy. On the basis of these results, it may be speculated that, albumin modified with endogenously generated methylglyoxal and peroxynitrite might be a driving factor in the progression of heightened inflammatory autoimmune responses. The work presents a ground to study the role of glyco-nitro-oxidized albumin in the pathogenesis and progression of various autoimmune diseases including rheumatoid arthritis. Communicated by Ramaswamy H. Sarma.

Hybrid Polymer Composite of Prussian Red Doped Polythiophene for Adsorptive Wastewater Treatment Application.

Coordination compounds as dopants to conducting polymers combine desirable properties of individual components for a synergistic effect. Prussian red (PR) a low spin iron (III) coordination compound was doped in polythiophene (PTP) matrix to explore propensity of this inorganic-organic hybrid composite material towards wastewater treatment. PR doping was observed to improve mechano, thermal, electrical, and photocatalytic attributes of pure PTP. PTP/PR composite characterization was attempted using the powder X-ray diffraction, TEM, TGA, FTIR, BET analysis and UV-Visible spectroscopy. Optimization of adsorption conditions, adsorbent regeneration, adsorption thermodynamics studies of PTP/PR were carried out using malachite green (MG) dye as a model system. Under optimized conditions 92% MG dye adsorption was observed over 20 mg PTP/PR nanocomposite in 20 minutes at pH 7. PTP/PR nanocomposite also demonstrated a complimentary performance with real wastewater samples. Thermodynamic studies indicate spontaneous process with electrostatic attraction as the predominant noncovalent interaction. This study highlights designing catalysts capable of synergistic adsorption and photocatalytic activities for effective wastewater treatment.

Pathophysiology of Depression: Stingless Bee Honey Promising as an Antidepressant.

Depression is a debilitating psychiatric disorder impacting an individual's quality of life. It is the most prevalent mental illness across all age categories, incurring huge socio-economic impacts. Most depression treatments currently focus on the elevation of neurotransmitters according to the monoamine hypothesis. Conventional treatments include tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), monoamine oxidase inhibitors (MAOIs), and serotonin reuptake inhibitors (SSRIs). Despite numerous pharmacological strategies utilising conventional drugs, the discovery of alternative medicines from natural products is a must for safer and beneficial brain supplement. About 30% of patients have been reported to show resistance to drug treatments coupled with functional impairment, poor quality of life, and suicidal ideation with a high relapse rate. Hence, there is an urgency for novel discoveries of safer and highly effective depression treatments. Stingless bee honey (SBH) has been proven to contain a high level of antioxidants compared to other types of honey. This is a comprehensive review of the potential use of SBH as a new candidate for antidepressants from the perspective of the monoamine, inflammatory and neurotrophin hypotheses.

Inhibition of Endoplasmic Reticulum Stress Improves Acetylcholine-Mediated Relaxation in the Aorta of Type-2 Diabetic Rats.

Endoplasmic reticulum (ER) stress contributes to insulin resistance and macro- and microvascular complications associated with diabetes. This study aimed to evaluate the effect of ER stress inhibition on endothelial function in the aorta of type-2 diabetic rats. Type-2 diabetes was developed in male Sprague-Dawley rats using a high-fat diet and low-dose streptozotocin. Rat aortic tissues were harvested to study endothelial-dependent relaxation. The mechanisms for acetylcholine-mediated relaxation were investigated using pharmacological blockers, Western blotting, oxidative stress, and inflammatory markers. Acetylcholine-mediated relaxation was diminished in the aorta of diabetic rats compared to control rats; supplementation with TUDCA improved relaxation. In the aortas of control and diabetic rats receiving TUDCA, the relaxation was mediated via eNOS/PI3K/Akt, NAD(P)H, and the KATP channel. In diabetic rats, acetylcholine-mediated relaxation involved eNOS/PI3K/Akt and NAD(P)H, but not the KATP channel. The expression of ER stress markers was upregulated in the aorta of diabetic rats and reduced with TUDCA supplementation. The expression of eNOS and Akt were lower in diabetic rats but were upregulated after supplementation with TUDCA. The levels of MDA, IL-6, and SOD activity were higher in the aorta of the diabetic rats compared to control rats. This study demonstrated that endothelial function was impaired in diabetes, however, supplementation with TUDCA improved the function via eNOS/Akt/PI3K, NAD(P)H, and the KATP channel. The improvement of endothelial function was associated with increased expressions of eNOS and Akt. Thus, ER stress plays a crucial role in the impairment of endothelial-dependent relaxation. Mitigating ER stress could be a potential strategy for improving endothelial dysfunction in type-2 diabetes.

Trends and challenges in phytotherapy and phytocosmetics for skin aging.

Oxidative stress and inflammation mostly contribute to aging and age-related conditions including skin aging. The potential of natural products in the form of naturally-derived cosmetics, cosmeceuticals, and nutricosmetics have, however, not been fully harnessed. This review, thus, critically analyzes the potential roles of natural products in inflammation-related skin aging diseases due to the increasing consumers' concerns and demands for efficacious, safe, natural, sustainable, and religiously permitted alternatives to synthetic products. The information and data were collated from various resources and literature databases such as PubMed, Science Direct, Wiley, Springer, Taylor and Francis, Scopus, Inflibnet, Google, and Google Scholar using relevant keywords and Medical Subject Headings (MeSH). The role of green extraction solvents as promising alternatives is also elucidated. The potential enhancements of the bioavailability, stability, solubility and controlled release profile of the bioactives using different delivery systems are also presented. The current potential global market value, motivators, drivers, trends, challenges, halal, and other regulatory certifications for cosmeceuticals and nutricosmetics are equally discussed. The adoption of the suggested extractions and delivery systems would enhance the stability, bioavailability, and target delivery of the bioactives.

Antioxidative Stress and Anti-Inflammatory Activity of Fucoidan Nanoparticles against Nephropathy of Streptozotocin-Induced Diabetes in Rats.

Oxidative stress and inflammation have been shown to interact and have the role of importance in causing diabetic nephropathy complications. Fucoidan has a strong antioxidant and anti-inflammation effect, so the aim of this research was to evaluate the antioxidative stress and anti-inflammatory effect of fucoidan nanoparticles against nephropathy of streptozotocin-induced diabetes in rats. Fucoidan nanoparticles are characterized using dynamic light scattering (DLS) and scanning electron microscope (SEM). The rats were randomized into the control group (were given with aquadest), streptozotocin group (were injected with streptozotocin at a dose of 55 mg/kg BW i.p.), and fucoidan nanoparticle group (were given orally with fucoidan at doses 75, 150, and 300 mg/kg BW and then injected streptozotocin at a dose of 55 mg/kg BW i.p.). The blood was taken to evaluate the level of blood urea nitrogen (BUN) and creatinine. The kidney tissues were collected to measure malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) by ELISA; superoxide dismutase (SOD), and glutathione peroxidase (GPx) by immunohistochemical staining and histological observation by Hematoxylin & Eosin (H&E) staining. The DLS demonstrated that the fucoidan nanoparticle size was 330.6 ± 58.8 nm, and the SEM showed an irregular shape with a rough surface image. The administration of streptozotocin significantly increased BUN, creatinine, MDA, IL-6, and TNF-α levels, whereas expression of SOD and GPx decreased as compared with the control group (p < 0.05). The administration of fucoidan nanoparticles only at a dose of 300 mg/kg BW significantly decreases BUN, creatinine, MDA, IL-6, and TNF-α levels. However, fucoidan nanoparticles at a dose of 300 mg/kg BW significantly increase SOD and GPx expression as compared with the streptozotocin group (p < 0.05). The administration of streptozotocin caused the loss of normal kidney cell structure and necrosis, while treatment with fucoidan nanoparticles improved renal cell necrosis. It can be concluded that fucoidan nanoparticles are promising agents in terms of the protection afforded against streptozotocin-induced nephropathy through antioxidative stress by decreasing MDA and increasing SOD and GPx and through anti-inflammatory effect by decreasing levels of IL-6 and TNF-α.

Magnetic exposure using Samarium Cobalt (SmCO5) increased proliferation and stemness of human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs).

Despite the extensive reports on the potential hazard of magnetic field (MF) exposures on humans, there are also concurrently reported on the improved proliferative property of stem cells at optimum exposure. However, the effect on mesenchymal stem cells (MSCs) remains unknown. Therefore, we aimed to investigate the impact of induced static MF (SMF) on human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) using Samarium Cobalt (SmCO5). At passage 3, hUC-MSCs (1 × 104) were exposed to 21.6 mT SMF by a direct exposure (DE) showed a significantly higher cell count (p < 0.05) in the growth kinetics assays with the shortest population doubling time relative to indirect exposure and negative control. The DE group was committed into the cell cycle with increased S phase (55.18 ± 1.38%) and G2/M phase (21.75 ± 1.38%) relative to the NC group [S-phase (13.54 ± 2.73%); G2/M phase (8.36 ± 0.28%)]. Although no significant changes were observed in the immunophenotype, the DE group showed an elevated expression of pluripotency-associated markers (OCT4, SOX2, NANOG, and REX1). These results suggest that the MFs could potentially induce proliferation of MSCs, a promising approach to promote stem cells propagation for clinical therapy and research without compromising the stemness of hUC-MSCs.

Antioxidative Stress and Antiapoptosis Effect of Chitosan Nanoparticles to Protect Cardiac Cell Damage on Streptozotocin-Induced Diabetic Rat.

The antioxidant can inhibit oxidative stress and apoptosis, which has a role in an important mechanism on diabetic-induced cardiac cell damage. The research goal was to prove the antioxidative stress and antiapoptosis effect of chitosan nanoparticles as a cardioprotector in streptozotocin-induced diabetic rats. Scanning electron microscope (SEM) and dynamic light scattering (DLS) characterize the chitosan nanoparticles. This research is a laboratory experiment which consists of the control group (rats were given distilled water), the streptozotocin group (rats were injected streptozotocin at dose of 55 mg/kg BW i.p), and the chitosan nanoparticle group (rats were given streptozotocin at dose 55 mg/kg BW i.p, and then given chitosan nanoparticles at dose 75 mg/kg BW, 150 mg/kg BW, and 300 mg/kg BW peroral). Creatine kinase-myoglobin (CK-MB) and lactate dehydrogenase (LDH) were measured from the blood sample. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) from cardiac tissue were examined by ELISA; nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated by western blotting; B-cell lymphoma 2 (Bcl-2) and Caspase-3 expression were investigated by immunohistochemical staining and also were evaluated histological preparation by hematoxylin & eosin (H&E) staining. The chitosan nanoparticles have a rough surface and an irregular shape. Its size is 247.3 ± 38.1 µm. Streptozotocin injection significantly increased the levels of CK-MB, LDH, MDA, and expression of caspase-3. In contrast, the levels of SOD, GPx, Nrf2, and expression of Bcl-2 decreased as compared with the control group (p < 0.05). This is accompanied by the loss of normal cardiac cell structure and necrosis. The administration of chitosan nanoparticles significantly reduced levels of CK-MB, LDH, MDA, and expression of Caspase-3. However, the levels of SOD, GPx, Nrf2, and expression of Bcl-2 increased as compared with the streptozotocin group (p < 0.05). And also, chitosan nanoparticles inhibited cell necrosis in diabetic rats. This study suggests that the administration of chitosan nanoparticles can protect cardiac cell damage in diabetic rats through antioxidative stress by decreasing ROS and increasing Nrf2 expression, level of SOD, and GPx and through antiapoptosis by increasing expression of Bcl-2 and decreasing expression of Caspase-3.

Correction: Alpha-Tomatine Attenuation of In Vivo Growth of Subcutaneous and Orthotopic Xenograft Tumors of Human Prostate Carcinoma PC-3 Cells Is Accompanied by Inactivation of Nuclear Factor-Kappa B Signaling.

[This corrects the article DOI: 10.1371/journal.pone.0057708.].

Dynamic response and low voltage ride-through enhancement of brushless double-fed induction generator using Salp swarm optimization algorithm.

A brushless double-fed induction generator (BDFIG) has shown tremendous success in wind turbines due to its robust brushless design, smooth operation, and variable speed characteristics. However, the research regarding controlling of machine during low voltage ride through (LVRT) need greater attention as it may cause total disconnection of machine. In addition, the BDFIG based wind turbines must be capable of providing controlled amount of reactive power to the grid as per modern grid code requirements. Also, a suitable dynamic response of machine during both normal and fault conditions needs to be ensured. This paper, as such, attempts to provide reactive power to the grid by analytically calculating the decaying flux and developing a rotor side converter control scheme accordingly. Furthermore, the dynamic response and LVRT capability of the BDFIG is enhanced by using one of the very intelligent optimization algorithms called the Salp Swarm Algorithm (SSA). To prove the efficacy of the proposed control scheme, its performance is compared with that of the particle swan optimization (PSO) based controller in terms of limiting the fault current, regulating active and reactive power, and maintaining the stable operation of the power system under identical operating conditions. The simulation results show that the proposed control scheme significantly improves the dynamic response and LVRT capability of the developed BDFIG based wind energy conversion system; thus proves its essence and efficacy.

Applications of Alginate-Based Nanomaterials in Enhancing the Therapeutic Effects of Bee Products.

Since the ancient times, bee products (i.e., honey, propolis, pollen, bee venom, bee bread, and royal jelly) have been considered as natural remedies with therapeutic effects against a number of diseases. The therapeutic pleiotropy of bee products is due to their diverse composition and chemical properties, which is independent on the bee species. This has encouraged researchers to extensively study the therapeutic potentials of these products, especially honey. On the other hand, amid the unprecedented growth in nanotechnology research and applications, nanomaterials with various characteristics have been utilized to improve the therapeutic efficiency of these products. Towards keeping the bee products as natural and non-toxic therapeutics, the green synthesis of nanocarriers loaded with these products or their extracts has received a special attention. Alginate is a naturally produced biopolymer derived from brown algae, the desirable properties of which include biodegradability, biocompatibility, non-toxicity and non-immunogenicity. This review presents an overview of alginates, including their properties, nanoformulations, and pharmaceutical applications, placing a particular emphasis on their applications for the enhancement of the therapeutic effects of bee products. Despite the paucity of studies on fabrication of alginate-based nanomaterials loaded with bee products or their extracts, recent advances in the area of utilizing alginate-based nanomaterials and other types of materials to enhance the therapeutic potentials of bee products are summarized in this work. As the most widespread and well-studied bee products, honey and propolis have garnered a special interest; combining them with alginate-based nanomaterials has led to promising findings, especially for wound healing and skin tissue engineering. Furthermore, future directions are proposed and discussed to encourage researchers to develop alginate-based stingless bee product nanomedicines, and to help in selecting suitable methods for devising nanoformulations based on multi-criteria decision making models. Also, the commercialization prospects of nanocomposites based on alginates and bee products are discussed. In conclusion, preserving original characteristics of the bee products is a critical challenge in developing nano-carrier systems. Alginate-based nanomaterials are well suited for this task because they can be fabricated without the use of harsh conditions, such as shear force and freeze-drying, which are often used for other nano-carriers. Further, conjunction of alginates with natural polymers such as honey does not only combine the medicinal properties of alginates and honey, but it could also enhance the mechanical properties and cell adhesion capacity of alginates.

Addressing the unfulfilled codex standard for honey for stingless bee honey through lyophilization.

Some studies have found that the nutritional values of stingless bee honey (SBH) may be similar if not more than normal honey, prompting the Malaysian government to promote it as a superfood. However, SBH does not fulfil the Codex Standard for Honey (CODEX STAN 12-19811) in terms of moisture content and the lack of protein to be analysed with Internal Standard Carbon Isotope Ratio Analysis (ISCIRA). Hence, a lyophilization process was introduced prior to stable carbon isotope analysis of SBH to address both of these issues. It was found that once moisture content was decreased to a level below 20 % for 19 SBH samples, the percentage increment of protein extracted from the samples varied between 6 and 385 % relative to protein extracted from SBH before lyophilization with nine samples found to be adulterated. Caution is necessary when lyophilizing the SBH as significant isotope shifts were seen for SCIRA and ISCIRA values. Nevertheless, the carbon isotope shifts did not change the final outcome of the 'pass' or 'fail' of the adulteration result. Overall, the removal of water from SBH is required but caution is necessary as carbon isotope shifts were observed as SBHs underwent the lyophilization process.

Thematic analysis of multiple sclerosis research by enhanced strategic diagram.

Recent interest in multiple sclerosis research warrants literature analysis to evaluate the current state of the discipline and new research domains. This bibliometric review summarised the research trends and analysed research areas in multiple sclerosis over the last decade. The documents containing the term 'multiple sclerosis' in the article title were retrieved from the Scopus database. We used Harzing's Publish or Perish and VOSviewer for citation analysis and data visualisation, respectively. We found a total of 18,003 articles published in journals in the English language between 2012 and 2021. The emerging keywords identified utilising the enhanced strategic diagram were 'covid-19', 'teriflunomide', 'clinical trial', 'microglia', 'b cells', 'myelin', 'brain', 'white matter', 'functional connectivity', 'pain', 'employment', 'health-related quality of life', 'meta-analysis' and 'comorbidity'. This study demonstrates the tremendous growth of multiple sclerosis literature worldwide, which is expected to grow more than double during the next decade especially in the identified emerging topics.

The potential neuroprotective effects of stingless bee honey.

Tropical Meliponini bees produce stingless bee honey (SBH). Studies have shown beneficial properties, including antibacterial, bacteriostatic, anti-inflammatory, neurotherapeutic, neuroprotective, wound, and sunburn healing capabilities. High phenolic acid and flavonoid concentrations offer SBH its benefits. SBH can include flavonoids, phenolic acids, ascorbic acid, tocopherol, organic acids, amino acids, and protein, depending on its botanical and geographic origins. Ursolic acid, p-coumaric acid, and gallic acid may diminish apoptotic signals in neuronal cells, such as nuclear morphological alterations and DNA fragmentation. Antioxidant activity minimizes reactive oxygen species (ROS) formation and lowers oxidative stress, inhibiting inflammation by decreasing enzymes generated during inflammation. Flavonoids in honey reduce neuroinflammation by decreasing proinflammatory cytokine and free radical production. Phytochemical components in honey, such as luteolin and phenylalanine, may aid neurological problems. A dietary amino acid, phenylalanine, may improve memory by functioning on brain-derived neurotrophic factor (BDNF) pathways. Neurotrophin BDNF binds to its major receptor, TrkB, and stimulates downstream signaling cascades, which are crucial for neurogenesis and synaptic plasticity. Through BDNF, SBH can stimulate synaptic plasticity and synaptogenesis, promoting learning and memory. Moreover, BDNF contributes to the adult brain's lasting structural and functional changes during limbic epileptogenesis by acting through the cognate receptor tyrosine receptor kinase B (TrkB). Given the higher antioxidants activity of SBH than the Apis sp. honey, it may be more therapeutically helpful. There is minimal research on SBH's neuroprotective effects, and the related pathways contribute to it is unclear. More research is needed to elucidate the underlying molecular process of SBH on BDNF/TrkB pathways in producing neuroprotective effects.