Metformin role in Parkinson's disease: a double-sword effect.

Parkinson's disease (PD) is a common neurodegenerative disease developed due to the degeneration of dopaminergic neurons in the substantia nigra. There is no single effective treatment in the management of PD. Therefore, repurposing effective and approved drugs like metformin could be an effective strategy for managing PD. However, the mechanistic role of metformin in PD neuropathology was not fully elucidated. Metformin is an insulin-sensitizing agent used as a first-line therapy in the management of type 2 diabetes mellitus (T2DM) and has the ability to reduce insulin resistance (IR). Metformin may have a beneficial effect on PD neuropathology. The neuroprotective effect of metformin is mainly mediated by activating adenosine monophosphate protein kinase (AMPK), which reduces mitochondrial dysfunction, oxidative stress, and α-synuclein aggregation. As well, metformin mitigates brain IR a hallmark of PD and other neurodegenerative diseases. However, metformin may harm PD neuropathology by inducing hyperhomocysteinemia and deficiency of folate and B12. Therefore, this review aimed to find the potential role of metformin regarding its protective and detrimental effects on the pathogenesis of PD. The mechanistic role of metformin in PD neuropathology was not fully elucidated. Most studies regarding metformin and its effectiveness in PD neuropathology were observed in preclinical studies, which are not fully translated into clinical settings. In addition, metformin effect on PD neuropathology was previously clarified in T2DM, potentially linked to an increasing PD risk. These limitations hinder the conclusion concerning the therapeutic efficacy of metformin and its beneficial and detrimental role in PD. Therefore, as metformin does not cause hypoglycemia and is a safe drug, it should be evaluated in non-diabetic patients concerning PD risk.

Depression and type 2 diabetes: A causal relationship and mechanistic pathway.

Depression is a mood disorder that may increase risk for the development of insulin resistance (IR) and type 2 diabetes (T2D), and vice versa. However, the mechanistic pathway linking depression and T2D is not fully elucidated. The aim of this narrative review, therefore, was to discuss the possible link between depression and T2D. The coexistence of T2D and depression is twice as great compared to the occurrence of either condition independently. Hyperglycaemia and dyslipidaemia promote the incidence of depression by enhancing inflammation and reducing brain serotonin (5-hydroxytryptamine [5HT]). Dysregulation of insulin signalling in T2D impairs brain 5HT signalling, leading to the development of depression. Furthermore, depression is associated with the development of hyperglycaemia and poor glycaemic control. Psychological stress and depression promote the development of T2D. In conclusion, T2D could be a potential risk factor for the development of depression through the induction of inflammatory reactions and oxidative stress that affect brain neurotransmission. In addition, chronic stress in depression may induce the development of T2D through dysregulation of the hypothalamic-pituitary-adrenal axis and increase circulating cortisol levels, which triggers IR and T2D.

Improved eco-friendly CsSn0.5Ge0.5I3 perovskite photovoltaic efficiency beyond 20% with SMe-TATPyr hole-transporting layer.

Perovskites composed of inorganic cesium (Cs) halide provide a route to thermally resistant solar cells. Nevertheless, the use of hole-transporting layers (HTLs) with hydrophobic additives is constrained by moisture-induced phase deterioration. Due to significant electrical loss, dopant-free HTLs are unable to produce practical solar cells. In this article, we designed a two-dimensional 1,3,6,8-tetrakis[5-(N,N-di(p-(methylthio)phenyl)amino-p-phenyl)-thiophen-2-yl]pyrene (termed SMe-TATPyr) molecule as a new HTL to regulate electrical loss in lead-free perovskite solar cells (PSCs). We optimized the power conversion efficiency (PCE) of PSCs based on mixed tin (Sn)/germanium (Ge) halide perovskite (CsSn0.5Ge0.5I3) by exploring different factors, such as the deep and shallow levels of defects, density of states at the valence band (NV), thickness of the perovskite film, p-type doping concentration (NA) of HTL, the series and shunt resistances, and so on. We carried out comparative research by employing the 1D-SCAPS (a solar cell capacitance simulator) analysis tool. Through optimization of the PSC, we obtained the highest parameters in the simulated solar cell structure of fluorine tin oxide (FTO)/titanium dioxide (TiO2)/CsSn0.5Ge0.5I3/SMe-TATPyr/gold (Au), and the PCE reached up to 20% with a fill factor (FF) of 81.89%.

NF-κB/NLRP3 inflammasome axis and risk of Parkinson's disease in Type 2 diabetes mellitus: A narrative review and new perspective.

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). Genetic predisposition and immune dysfunction are involved in the pathogenesis of PD. Notably, peripheral inflammatory disorders and neuroinflammation are associated with PD neuropathology. Type 2 diabetes mellitus (T2DM) is associated with inflammatory disorders due to hyperglycaemia-induced oxidative stress and the release of pro-inflammatory cytokines. Particularly, insulin resistance (IR) in T2DM promotes the degeneration of dopaminergic neurons in the substantia nigra (SN). Thus, T2DM-induced inflammatory disorders predispose to the development and progression of PD, and their targeting may reduce PD risk in T2DM. Therefore, this narrative review aims to find the potential link between T2DM and PD by investigating the role of inflammatory signalling pathways, mainly the nuclear factor kappa B (NF-κB) and the nod-like receptor pyrin 3 (NLRP3) inflammasome. NF-κB is implicated in the pathogenesis of T2DM, and activation of NF-κB with induction of neuronal apoptosis was also confirmed in PD patients. Systemic activation of NLRP3 inflammasome promotes the accumulation of α-synuclein and degeneration of dopaminergic neurons in the SN. Increasing α-synuclein in PD patients enhances NLRP3 inflammasome activation and the release of interleukin (IL)-1ß followed by the development of systemic inflammation and neuroinflammation. In conclusion, activation of the NF-κB/NLRP3 inflammasome axis in T2DM patients could be the causal pathway in the development of PD. The inflammatory mechanisms triggered by activated NLRP3 inflammasome lead to pancreatic ß-cell dysfunction and the development of T2DM. Therefore, attenuation of inflammatory changes by inhibiting the NF-κB/NLRP3 inflammasome axis in the early T2DM may reduce future PD risk.

Electrospun Polycaprolactone/Chitosan Nanofibers Containing Cordia myxa Fruit Extract as Potential Biocompatible Antibacterial Wound Dressings.

The goal of the current work was to create an antibacterial agent by using polycaprolactone/chitosan (PCL/CH) nanofibers loaded with Cordia myxa fruit extract (CMFE) as an antimicrobial agent for wound dressing. Several characteristics, including morphological, physicomechanical, and mechanical characteristics, surface wettability, antibacterial activity, cell viability, and in vitro drug release, were investigated. The inclusion of CMFE in PCL/CH led to increased swelling capability and maximum weight loss. The SEM images of the PCL/CH/CMFE mat showed a uniform topology free of beads and an average fiber diameter of 195.378 nm. Excellent antimicrobial activity was shown towards Escherichia coli (31.34 ± 0.42 mm), Salmonella enterica (30.27 ± 0.57 mm), Staphylococcus aureus (21.31 ± 0.17 mm), Bacillus subtilis (27.53 ± 1.53 mm), and Pseudomonas aeruginosa (22.17 ± 0.12 mm) based on the inhibition zone assay. The sample containing 5 wt% CMFE had a lower water contact angle (47 ± 3.7°), high porosity, and high swelling compared to the neat mat. The release of the 5% CMFE-loaded mat was proven to be based on anomalous non-Fickian diffusion using the Korsmeyer-Peppas model. Compared to the pure PCL membrane, the PCL-CH/CMFE membrane exhibited suitable cytocompatibility on L929 cells. In conclusion, the fabricated antimicrobial nanofibrous films demonstrated high bioavailability, with suitable properties that can be used in wound dressings.

Galangin/ß-Cyclodextrin Inclusion Complex as a Drug-Delivery System for Improved Solubility and Biocompatibility in Breast Cancer Treatment.

The purpose of this study was to evaluate the potential of a newly modified cyclodextrin derivative, water-soluble ß-cyclodextrin-epichlorohydrin (ß-CD), as an effective drug carrier to enhance the poor solubility and bioavailability of galangin (GAL), a poorly water-soluble model drug. In this regard, inclusion complexes of GAL/ß-CDP were prepared. UV-VIS spectrophotometry, Fourier-transform infrared spectroscopy (FTIR), X-ray crystallography (XRD), zeta potential analysis, particle size analysis, field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM) were applied to characterize the synthesized GAL/ß-CD. Michigan Cancer Foundation-7 (MCF-7; human breast cancer cells) and rat embryo fibroblast (REF; normal cells) were employed to examine the in vitro cytotoxic effects of GAL/ß-CD using various parameters. The dye-based tests of MTT and crystal violet clearly exhibited that GAL/ß-CD-treated cells had a reduced proliferation rate, an influence that was not found in the normal cell line. The cells' death was found to follow apoptotic mechanisms, as revealed by the dye-based test of acridine orange/ethidium bromide (AO/EtBr), with the involvement of the mitochondria via caspase-3-mediated events, as manifested by the Rh 123 test. We also included a mouse model to examine possible in vivo toxic effects of GAL/ß-CD. It appears that the inclusion complex does not have a significant influence on normal cells, as indicated by serum levels of kidney and liver enzymatic markers, as well as thymic and splenic mass indices. A similar conclusion was reached on the histological level, as manifested by the absence of pathological alterations in the liver, kidney, thymus, spleen, heart, and lung.

Polyethylene Glycol Functionalized Graphene Oxide Nanoparticles Loaded with Nigella sativa Extract: A Smart Antibacterial Therapeutic Drug Delivery System.

Flaky graphene oxide (GO) nanoparticles (NPs) were synthesized using Hummer's method and then capped with polyethylene glycol (PEG) by an esterification reaction, then loaded with Nigella sativa (N. sativa) seed extract. Aiming to investigate their potential use as a smart drug delivery system against Staphylococcus aureus and Escherichia coli, the spectral and structural characteristics of GO-PEG NPs were comprehensively analyzed by XRD, AFM, TEM, FTIR, and UV- Vis. XRD patterns revealed that GO-PEG had different crystalline structures and defects, as well as a higher interlayer spacing. AFM results showed GONPs with the main grain size of 24.41 nm, while GONPs-PEG revealed graphene oxide aggregation with the main grain size of 287.04 nm after loading N. sativa seed extract, which was verified by TEM examination. A strong OH bond appeared in FTIR spectra. Furthermore, UV- Vis absorbance peaks at (275, 284, 324, and 327) nm seemed to be correlated with GONPs, GO-PEG, N. sativa seed extract, and GO -PEG- N. sativa extract. The drug delivery system was observed to destroy the bacteria by permeating the bacterial nucleic acid and cytoplasmic membrane, resulting in the loss of cell wall integrity, nucleic acid damage, and increased cell-wall permeability.

IL-33 promotes ST2-dependent lung fibrosis by the induction of alternatively activated macrophages and innate lymphoid cells in mice.

BACKGROUND: The initiation and regulation of pulmonary fibrosis are not well understood. IL-33, an important cytokine for respiratory diseases, is overexpressed in the lungs of patients with idiopathic pulmonary fibrosis. OBJECTIVES: We aimed to determine the effects and mechanism of IL-33 on the development and severity of pulmonary fibrosis in murine bleomycin-induced fibrosis. METHODS: Lung fibrosis was induced by bleomycin in wild-type or Il33r (St2)(-/-) C57BL/6 mice treated with the recombinant mature form of IL-33 or anti-IL-33 antibody or transferred with type 2 innate lymphoid cells (ILC2s). The development and severity of fibrosis was evaluated based on lung histology, collagen levels, and lavage cytology. Cytokine and chemokine levels were quantified by using quantitative PCR, ELISA, and cytometry. RESULTS: IL-33 is constitutively expressed in lung epithelial cells but is induced in macrophages by bleomycin. Bleomycin enhanced the production of the mature but reduced full-length form of IL-33 in lung tissue. ST2 deficiency, anti-IL-33 antibody treatment, or alveolar macrophage depletion attenuated and exogenous IL-33 or adoptive transfer of ILC2s enhanced bleomycin-induced lung inflammation and fibrosis. These pathologic changes were accompanied, respectively, by reduced or increased IL-33, IL-13, TGF-ß1, and inflammatory chemokine production in the lung. Furthermore, IL-33 polarized M2 macrophages to produce IL-13 and TGF-ß1 and induced the expansion of ILC2s to produce IL-13 in vitro and in vivo. CONCLUSIONS: IL-33 is a novel profibrogenic cytokine that signals through ST2 to promote the initiation and progression of pulmonary fibrosis by recruiting and directing inflammatory cell function and enhancing profibrogenic cytokine production in an ST2- and macrophage-dependent manner.

New insight on the possible role of statins in Vascular Parkinsonism: A need for presumptive therapy.

Vascular Parkinsonism (VP) is clinical term represents a progressive ischemic changes and subcortical lacunar infarct leading to Parkinsonism mainly in the lower limbs so called lower body Parkinsonism. The VP neuropathology is differed from that of PD neuropathology which rarely associated with basal ganglion lesions. Dopamine transporters are normal in VP but are highly reduced in PD, and dopaminergic agonists had no effective role on VP. The neuropathological mechanisms of VP are related to vascular injury which induces the interruption of the neural connection between basal ganglion and cerebral cortex. Hyperlipidemia and other cardiometabolic risk factors augment VP risk and the related neuropathology. Targeting of these cardiometabolic disorders by lipid-lowering statins may be effective in the management of VP. Therefore, this mini-review aims to clarify the possible role of statins in the management of VP. Statins have neuroprotective effects against different neurodegenerative diseases by anti-inflammatory, antioxidant and antithrombotic effects with enhancement of endothelial function. In conclusion, statins can prevent and treat VP by inhibiting inflammatory and oxidative stress disorders, mitigating of white matter hyperintensities and improving of neuronal signaling pathways. Additional preclinical, clinical trials and prospective studies are warranted in this regard.

Dysregulation of pancreatic ß-cell autophagy and the risk of type 2 diabetes.

Macroautophagy/autophagy is an essential degradation process that removes abnormal cellular components, maintains homeostasis within cells, and provides nutrition during starvation. Activated autophagy enhances cell survival during stressful conditions, although overactivation of autophagy triggers induction of autophagic cell death. Therefore, early-onset autophagy promotes cell survival whereas late-onset autophagy provokes programmed cell death, which can prevent disease progression. Moreover, autophagy regulates pancreatic ß-cell functions by different mechanisms, although the precise role of autophagy in type 2 diabetes (T2D) is not completely understood. Consequently, this mini-review discusses the protective and harmful roles of autophagy in the pancreatic ß cell and in the pathophysiology of T2D.

Fabrication of pure Bi2WO6 and Bi2WO6/MWCNTs nanocomposite as potential antibacterial and anticancer agents.

An essential research area for scientists is the development of high-performing, inexpensive, non-toxic antibacterial materials that prevent the transfer of bacteria. In this study, pure Bi2WO6 and Bi2WO6/MWCNTs nanocomposite were prepared by hydrothermal method. A series of characterization results by using XRD FTIR, Raman, FESEM, TEM, and EDS analyses, reveal the formation of orthorhombic nanoflakes Bi2WO6 by the addition of NaOH and pH adjustment to 7. Compared to pure Bi2WO6, the Bi2WO6/MWCNTs nanocomposite exhibited that CNTs are efficiently embedded into the structure of Bi2WO6 which results in charge transfer between metal ion electrons and the conduction or valence band of Bi2WO6 and MWCNTs and result in shifting to longer wavelength as shown in UV-visible and PL. The results confirmed that MWCNTs are stuck to the surface of the microflowers, and some of them embedded inside the Bi2WO6 nanoflakes without affecting the structure of Bi2WO6 nanoflakes as demonstrated by TEM. In addition, Pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite were tested against P. mirabilis and S. mutans., confirming the effect of addition MWCNTs materials had better antibacterial activity in opposition to both bacterial strains than pure Bi2WO6. Besides, pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite tested for cytotoxicity against lung MTT test on Hep-G2 liver cancer cells, and flow-cytometry. Results indicated that pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite have significant anti-cancer efficacy against Hep-G2 cells in vitro. In addition, the findings demonstrated that Bi2WO6 and Bi2WO6/MWCNTs triggered cell death via increasing ROS. Based on these findings, it appears that pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite have the potential to be developed as nanotherapeutics for the treatment of bacterial infections, and liver cancer.

The beneficial role of autophagy in multiple sclerosis: Yes or No?

Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system (CNS) due to an increase of abnormal peripherally auto-reactive T lymphocytes which elicit autoimmunity. The main pathophysiology of MS is myelin sheath damage by immune cells and a defect in the generation of myelin by oligodendrocytes. Macroautophagy/autophagy is a critical degradation process that eliminates dysfunctional or superfluous cellular components. Autophagy has the property of a double-edged sword in MS in that it may have both beneficial and detrimental effects on MS neuropathology. Therefore, this review illustrates the protective and harmful effects of autophagy with regard to this disease. Autophagy prevents the progression of MS by reducing oxidative stress and inflammatory disorders. In contrast, over-activated autophagy is associated with the progression of MS neuropathology and in this case the use of autophagy inhibitors may alleviate the pathogenesis of MS. Furthermore, autophagy provokes the activation of different immune and supporting cells that play an intricate role in the pathogenesis of MS. Autophagy functions in the modulation of MS neuropathology by regulating cell proliferation related to demyelination and remyelination. Autophagy enhances remyelination by increasing the activity of oligodendrocytes, and astrocytes. However, autophagy induces demyelination by activating microglia and T cells. In conclusion, specific autophagic activators of oligodendrocytes, and astrocytes, and specific autophagic inhibitors of dendritic cells (DCs), microglia and T cells induce protective effects against the pathogenesis of MS.Abbreviations: ALS: amyotrophic lateral sclerosis; APCs: antigen-presenting cells; BBB: blood-brain barrier; CSF: cerebrospinal fluid; CNS: central nervous system; DCs: dendritic cells; EAE: experimental autoimmune encephalomyelitis; ER: endoplasmic reticulum; LAP: LC3-associated phagocytosis; MS: multiple sclerosis; NCA: non-canonical autophagy; OCBs: oligoclonal bands; PBMCs: peripheral blood mononuclear cells; PD: Parkinson disease; ROS: reactive oxygen species; UPR: unfolded protein response.

Synthesis, pharmacological evaluation, and in silico study of new 3-furan-1-thiophene-based chalcones as antibacterial and anticancer agents.

New 3-furan-1-thiophene-based chalcones were synthesized, characterized and pharmacologically evaluated as antibacterial and anticancer agents against two bacterial species; Gram-positive (Streptococcus pyogenes) and Gram-negative (Pseudomonas aeruginosa). All tested final compounds were active against the two bacterial species; S. pyogenes and P . aeruginosa. Especially compound AM4 showed large inhibition zone (27.13 and 23.30 mm), respectively. Using the DPPH assay, the new chalcones were evaluated for their free radical scavenging activity and found to reach up to 90 %, accomplished at a test concentration of 200 µg/mL. Furthermore, the chalcone derivatives were investigated against two breast cell lines; MCF-7 (cancerous) and MCF-10A (non-cancerous). Compound AM4 showed potent anticancer activity (IC50 = 19.354 µg/mL) in comparison to the other tested chalcone derivatives. In silico study was achieved using the PyRx AutoDock Vina software (0.8) to study the interaction types between the new hits and the binding sites of targeted proteins; glucosamine-6-phosphate synthase and tubulin, the target for antibacterial and anticancer drugs, respectively. Based on the molecular docking results the tested chalcones bind to the active pocket of the respective proteins, which support the in vitro results. In conclusion, 3-furan-1-thiophene-based chalcones could serve as new hits in the discovery of novel anticancer and/or antibacterial drugs.

The classical and non-classical axes of renin-angiotensin system in Parkinson disease: The bright and dark side of the moon.

Parkinson disease (PD) is a common brain neurodegenerative disease due to progressive degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). Of note, the cardio-metabolic disorders such as hypertension are adversely affect PD neuropathology through exaggeration of renin-angiotensin system (RAS). The RAS affects the stability of dopaminergic neurons in the SNpc, and exaggeration of angiotensin II (AngII) is implicated in the development and progression of PD. RAS has two axes classical including angiotensin converting enzyme (ACE)/AngII/AT1R, and the non-classical axis which include ACE2/Ang1-7/Mas receptor, AngIII, AngIV, AT2R, and AT4R. It has been shown that brain RAS is differs from that of systemic RAS that produce specific neuronal effects. As well, there is an association between brain RAS and PD. Therefore, this review aims to revise from published articles the role of brain RAS in the pathogenesis of PD focusing on the non-classical pathway, and how targeting of this axis can modulate PD neuropathology.

Role of ketogenic diet in neurodegenerative diseases focusing on Alzheimer diseases: The guardian angle.

The ketogenic diet (KD) is a low-carbohydrate, adequate protein and high-fat diet. KD is primarily used to treat refractory epilepsy. KD was shown to be effective in treating different neurodegenerative diseases. Alzheimer disease (AD) is the first common neurodegenerative disease in the world characterized by memory and cognitive impairment. However, the underlying mechanism of KD in controlling of AD and other neurodegenerative diseases are not discussed widely. Therefore, this review aims to revise the fundamental mechanism of KD in different neurodegenerative diseases focusing on the AD. KD induces a fasting-like which modulates the central and peripheral metabolism by regulating mitochondrial dysfunction, oxidative stress, inflammation, gut-flora, and autophagy in different neurodegenerative diseases. Different studies highlighted that KD improves AD neuropathology by regulating synaptic neurotransmission and inhibiting of neuroinflammation and oxidative stress. In conclusion, KD improves cognitive function and attenuates the progression of AD neuropathology by reducing oxidative stress, mitochondrial dysfunction, and enhancing neuronal autophagy and brain BDNF.

Defective autophagy and autophagy activators in myasthenia gravis: a rare entity and unusual scenario.

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ) that results from autoantibodies against nicotinic acetylcholine receptors (nAchRs) at NMJs. These autoantibodies are mainly originated from autoreactive B cells that bind and destroy nAchRs at NMJs preventing nerve impulses from activating the end-plates of skeletal muscle. Indeed, immune dysregulation plays a crucial role in the pathogenesis of MG. Autoreactive B cells are increased in MG due to the defect in the central and peripheral tolerance mechanisms. As well, autoreactive T cells are augmented in MG due to the diversion of regulatory T (Treg) cells or a defect in thymic anergy leading to T cell-mediated autoimmunity. Furthermore, macroautophagy/autophagy, which is a conserved cellular catabolic process, plays a critical role in autoimmune diseases by regulating antigen presentation, survival of immune cells and cytokine-mediated inflammation. Abnormal autophagic flux is associated with different autoimmune disorders. Autophagy regulates the connection between innate and adaptive immune responses by controlling the production of cytokines and survival of Tregs. As autophagy is involved in autoimmune disorders, it may play a major role in the pathogenesis of MG. Therefore, this mini-review demonstrates the potential role of autophagy and autophagy activators in MG.Abbreviations: Ach, acetylcholine; Breg, regulatory B; IgG, immunoglobulin G; MG, myasthenia gravis; NMJ, neuromuscular junction; ROS, reactive oxygen species; Treg, regulatory T; Ubl, ubiquitin-like.

Liposome Nanocarriers Based on γ Oryzanol: Preparation, Characterization, and In Vivo Assessment of Toxicity and Antioxidant Activity.

The present study aimed to develop and characterize liposome nanocarriers based on γ oryzanol and evaluate their potential in vitro and in vivo toxicity and antioxidant effects. The liposomes were physicochemically characterized using various techniques, including dynamic light scattering (DLS) for size and polydispersity index (PDI) measurements and ζ-potential analysis. The in vitro toxicity assessments were performed using hemolysis and MTT assays on the HS5 cell line. In vivo, acute oral toxicity was evaluated by using LD50 assays in mice. Additionally, antioxidant activity was assessed through biochemical analysis of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and liver tissue catalase, malondialdehyde (MDA), and glutathione (GSH) levels. The results revealed that the liposomes exhibited a uniform and spherical morphology with suitable physicochemical properties for drug delivery applications. The in vitro cytotoxicity and hemolysis assays and the in vivo LD50 experiment indicated the potential safety of γ oryzanol liposomes, especially at lower concentrations. In addition, the assessment of liver enzymes, i.e., ALT and AST, and the antioxidant markers further revealed the safety of the formulation, particularly for the liver as a highly sensitive soft organ. Overall, the liposome nanocarriers based on γ oryzanol were successfully formulated and expressed potential safety, supporting their application for the purposes of drug delivery and therapeutic interventions, particularly for hepatocellular and antioxidant therapies; however, further investigations for preclinical and clinical studies could be the future prospects for liposome nanocarriers based on γ oryzanol to explore the safety and efficacy of these nanocarriers in various disease models and clinical settings.

A theoretical investigation for improving the performance of non-fullerene organic solar cells through side-chain engineering of BTR non-fused-ring electron acceptors.

In the current quantum chemical study, indacenodithiophene donor core-based the end-capped alterations of the reference chromophore BTR drafted eight A2-A1-D-A1-A2 type small non-fullerene acceptors. All the computational simulations were executed under MPW1PW91/6-31G (d, p) level of DFT. The UV-Vis absorption, open circuit voltage, electron affinity, ionization potential, the density of states, reorganization energy, orbital analysis, and non-covalent interactions were studied and compared with BTR. Several molecules of our modeled series BT1-BT8 have shown distinctive features that are better than those of the BTR. The open circuit voltage (VOC) of BT5 has a favorable impact, allowing it to replace BTR in the field of organic solar cells. The charge carrier motilities for proposed molecules generated extraordinary findings when matched to the reference one (BTR). Further charge transmission was confirmed by creating the complex with a PM6 donor molecule. The remarkable dipole moment contributes to the formation of non-covalent bond interactions with chloroform, resulting in superior charge mobility. Based on these findings, it can be said that every tailored molecule has the potential to surpass chromophore molecule (BTR) in OSCs. So, all tailored molecules may enhance the efficiency of photovoltaic cells due to the involvement of potent terminal electron-capturing acceptor2 moieties. Considering these obtained results, these newly presented molecules can be regarded for developing efficient solar devices in the future.

The role of statins in amyotrophic lateral sclerosis: protective or not?

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons characterized by muscle weakness, muscle twitching, and muscle wasting. ALS is regarded as the third-most frequent neurodegenerative disease, subsequent to Alzheimer's disease (AD) and Parkinson's disease (PD). The World Health Organization (WHO) in 2007 declared that prolonged use of statins may induce development of ALS-like syndrome and may increase ALS risk. Subsequently, different studies have implicated statins in the pathogenesis of ALS. In contrast, results from preclinical and clinical studies highlighted the protective role of statins against ALS neuropathology. Recently, meta-analyses and systematic reviews illustrated no association between long-term use of statins and ALS risk. These findings highlighted controversial points regarding the effects of statins on ALS pathogenesis and risk. The neuroprotective effects of statins against the development and progression of ALS may be mediated by regulating dyslipidemia and inflammatory changes. However, the mechanism for induction of ALS neuropathology by statins may be related to the dysregulation of liver X receptor signaling (LXR) signaling in the motor neurons and reduction of cholesterol, which has a neuroprotective effect against ALS neuropathology. Nevertheless, the exact role of statins on the pathogenesis of ALS was not fully elucidated. Therefore, this narrative review aims to discuss the role of statins in ALS neuropathology.

Breaking Barriers: Nucleic Acid Aptamers in Gastrointestinal (GI) Cancers Therapy.

Conventional cancer therapies can have significant adverse effects as they are not targeted to cancer cells and may damage healthy cells. Single-stranded oligonucleotides assembled in a particular architecture, known as aptamers, enable them to attach selectively to target areas. Usually, they are created by Systematic Evolution of Ligand by Exponential enrichment (SELEX), and they go through a rigorous pharmacological revision process to change their therapeutic half-life, affinity, and specificity. They could thus offer a viable substitute for antibodies in the targeted cancer treatment market. Although aptamers can be a better choice in some situations, antibodies are still appropriate for many other uses. The technique of delivering aptamers is simple and reasonable, and the time needed to manufacture them is relatively brief. Aptamers do not require animals or an immune response to be produced, in contrast to antibodies. When used as a medication, aptamers can directly suppress tumor cells. As an alternative, they can be included in systems for targeted drug delivery that administer medications specifically to tumor cells while reducing toxicity to healthy cells. The most recent and cutting-edge methods for treating gastrointestinal (GI) tract cancer with aptamers will be covered in this review, with a focus on targeted therapy as a means of conquering resistance to traditional medicines.