The compelling role of allopurinol in hyperuricemia-induced epilepsy: Unrecognized like tears in rain.

Epilepsy is a common neurological disease characterized by the recurrent, paroxysmal, and unprovoked seizures. It has been shown that hyperuricemia enhances and associated with the development and progression of epilepsy through induction of inflammation and oxidative stress. In addition, uric acid is released within the brain and contributes in the development of neuronal hyperexcitability and epileptic seizure. Brain uric acid acts as damage associated molecular pattern (DAMP) activates the immune response and induce the development of neuroinflammation. Therefore, inhibition of xanthine oxidase by allopurinol may reduce hyperuricemia-induced epileptic seizure and associated oxidative stress and inflammation. However, the underlying mechanism of allopurinol in the epilepsy was not fully elucidated. Therefore, this review aims to revise from published articles the link between hyperuricemia and epilepsy, and how allopurinol inhibits the development of epileptic seizure.

New insights on testicular cancer prevalence with novel diagnostic biomarkers and therapeutic approaches.

BACKGROUND: Testicular cancer (TC), comprising merely 1% of male neoplasms, holds the distinction of being the most commonly encountered neoplasm among young males. RECENT FINDINGS: Most cases of testicular neoplasms can be classified into two main groups, namely germ cell tumors representing approximately 95% of the cases, and sex cord-stromal tumors accounting for about 5% of the cases. Moreover, its prevalence is on the rise across the globe. TC is a neoplastic condition characterized by a favorable prognosis. The advent of cisplatin-based chemotherapeutic agents in the latter part of the 1970s has led to a significant enhancement in the 5-year survival rate, which presently surpasses 95%. Given that TC is commonly detected before reaching the age of 40, it can be anticipated that these individuals will enjoy an additional 40-50 years of life following successful treatment. The potential causes of TC are multifactorial and related to different pathologies. Accurate identification is imperative to guarantee the utmost efficacious and suitable therapy. To a certain degree, this can be accomplished through the utilization of blood examinations for neoplastic indicators; nonetheless, an unequivocal diagnosis necessitates an evaluation of the histological composition of a specimen via a pathologist. CONCLUSION: TC is multifactorial and has various pathologies, therefore this review aimed to revise the prenatal and postnatal causes as well as novel diagnostic biomarkers and the therapeutic strategies of TC.

The therapeutic value of Myrtus communis L.: an updated review.

Myrtus communis L. (Family: Myrtaceae) is naturally found in the western part of Asia, Southern Europe, and North Africa. It has been reportedly applied in pharmaceutical industry, traditional medicine, cosmetics, spices, and food. Pubmed, Google scholar, Web of Science, and Scopus were utilized to seek out relevant content concerning the therapeutic potential of M. communis. Subsequently, we conducted a review to identity noteworthy updates pertaining to M. communis. Myrtle berries, leaves, seeds, and essential oils are natural sources of several nutrients and bioactive compounds with marked health effects. The chemical analysis showed that M. communis contained oils, alkaloids, flavonoids, phenolics, coumarins, saponosides, tannins, quinines, and anthraquinones. A pharmacological investigation revealed that M. communis possessed anti-inflammatory, analgesic, antimicrobial, antiparasitic, antioxidant, antidiabetic, anticancer, antimutagenic, immunomodulatory, dermatological, cardiovascular, central nervous system, and gastrointestinal protective effects, among numerous other biological effects. This current review focused on the biochemical, pharmacological, therapeutic effects, and various biological activities of different parts of M. communis. It signifies that M. communis is a therapeutic plant with numerous applications in medicine and could be used as a drug isolate based on its safety and effectiveness.

Chemical profile and evaluation of the pharmacological activity of the dry extract and fraction of ethyl acetate obtained from the leaves of Mimosa caesalpiniifolia.

ETHNOPHARMACOLOGICAL RELEVANCE: Mimosa caesalpiniifolia (Sansão-do-Campo) is a native species of the caatinga in northeastern Brazil that has been studied for its potential anti-inflammatory and antidepressant activity. It is popularly consumed as a medicinal plant and its pharmacological benefits are evidenced in the literature. AIM OF THE STUDY: The present work was carried out to promote the chemical profile and evaluate the pharmacological activity of the dry extract and the ethyl acetate fraction obtained from the dry leaves of Mimosa caesalpiniifolia. MATERIALS AND METHODS: The leaves were collected in the municipality of Alfenas-MG and subjected to drying, followed by division in a knife mill. The preparation of the dry extract was carried out by the extraction method using simple percolation and the fraction was obtained by liquid-liquid partition. Part of the extractive solution was concentrated in a rotary evaporator followed by a drying process using the spray technique with the addition of colloidal silicon dioxide. The dry extract (33.33%) showed a higher yield in mass when compared to the yield of the ethyl acetate fraction (19.67%). The in vivo pharmacological evaluation was conducted with a total of 82 male Wistar rats that underwent cecal ligation and perforation surgery to induce the inflammatory process. One week after surgery, these animals were treated for 7 days with the dry extract and the ethyl acetate fraction and submitted to behavioral tests (open field and forced swimming). RESULTS: The chemical results were obtained through analysis by HPLC-PDA coupled to a mass spectrometer, enabling the verification of the presence of phenolic acids, flavonoids, aglycones, and glycosides, in addition to tannins. This corroborates with data present in the literature for the genus Mimosa sp. Some compounds had their structure determined, where they were identified as catechin (m/z 288.97), cassiaocidentalin A (m/z 560.75), and procyanidin B2 [(epi)catechin-(epi)catechin; m/z 576.83)]. It was found that the animals that were submitted to the treatment did not present statistically significant results, demonstrating that the pharmacological action evaluated in the test was not highlighted in this type of experiment. The groups that underwent treatment had an aggravated locomotor activity. CONCLUSIONS: The results found with the chemical study contributed to the knowledge of the plant species studied. On the other hand, further studies are needed to provide a better understanding of the pharmacological evaluation of Mimosa caesalpiniifolia.

Uncovering the antimicrobial activity of G-type lysozyme 2 derived from Cyprinus carpio mucus against bacterial and fungal pathogens.

This study aimed to explore the antimicrobic potential of mucus samples collected from Cyprinus carpio and identify the specific antimicrobial peptides responsible for its activity. The crude extract was tested against various bacterial and fungal pathogens, and its protein content and profile were analyzed. Purification steps, including gel filtration chromatography, were employed to isolate the most active fraction (peak IV), which was further identified via liquid chromatography and mass spectroscopy. The results revealed varying degrees of antimicrobial activity of the crude extract against different bacterial and fungal strains, with Leclercia adecarboxylata, Candida glabrata, and Candida parapsilosis showing the highest susceptibility. SDS-PAGE analysis demonstrated the existence of multiple low molecular weight protein bands in the crude extract, while fraction IV obtained from gel filtration chromatography exhibited the strongest antimicrobial activity. Peak IV displayed a range of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) values against the tested pathogens, spanning from 0.038 to 4.960 mg/mL. Further investigation identified the purified peptide derived from peak IV as G-type lysozyme 2, characterized by a molecular weight of 21 kDa. These findings shed light on the existence of a highly effective antimicrobial peptide, G-type lysozyme 2, within the mucus of Cyprinus carpio. This peptide demonstrates notable activity against diverse bacterial and fungal pathogens. The insights from this study enhance our understanding of the fish's antimicrobial defense mechanisms and hold promise for developing novel antimicrobial agents.

Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective.

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease with multifaceted neuropathological disorders. AD is characterized by intracellular accumulation of phosphorylated tau proteins and extracellular deposition of amyloid beta (Aß). Various protease enzymes, including neprilysin (NEP), are concerned with the degradation and clearance of Aß. Indeed, a defective neuronal clearance pathway due to the dysfunction of degradation enzymes might be a possible mechanism for the accumulation of Aß and subsequent progression of AD neuropathology. NEP is one of the most imperative metalloproteinase enzymes involved in the clearance of Aß. This review aimed to highlight the possible role of NEP inhibitors in AD. The combination of sacubitril and valsartan which is called angiotensin receptor blocker and NEP inhibitor (ARNI) may produce beneficial and deleterious effects on AD neuropathology. NEP inhibitors might increase the risk of AD by the inhibition of Aß clearance, and increase brain bradykinin (BK) and natriuretic peptides (NPs), which augment the pathogenesis of AD. These verdicts come from animal model studies, though they may not be applied to humans. However, clinical studies revealed promising safety findings regarding the use of ARNI. Moreover, NEP inhibition increases various neuroprotective peptides involved in inflammation, glucose homeostasis and nerve conduction. Also, NEP inhibitors may inhibit dipeptidyl peptidase 4 (DPP4) expression, ameliorating insulin and glucagon-like peptide 1 (GLP-1) levels. These findings proposed that NEP inhibitors may have a protective effect against AD development by increasing GLP-1, neuropeptide Y (NPY) and substance P, and deleterious effects by increasing brain BK. Preclinical and clinical studies are recommended in this regard.

The possible role furin and furin inhibitors in endometrial adenocarcinoma: A narrative review.

BACKGROUND: Endometrial adenocarcinoma (EAC) is a malignant tumor of the endometrium. EAC is the most common female malignancy following the menopause period. About 40% of patients with EAC are linked with obesity and interrelated with hypertension, diabetes mellitus, and high circulating estrogen levels. Proprotein convertase (PC) furin was involved in the progression of EAC. RECENT FINDINGS: Furin is a protease enzyme belonging to the subtilisin PC family called PC subtilisin/kexin type 3 that converts precursor proteins to biologically active forms and products. Aberrant activation of furin promotes abnormal cell proliferation and the development of cancer. Furin promotes angiogenesis, malignant cell proliferation, and tissue invasion by malignant cells through its pro-metastatic and oncogenic activities. Furin activity is correlated with the malignant proliferation of EAC. Higher expression of furin may increase the development of EAC through overexpression of pro-renin receptors and disintegrin and metalloprotease 17 (ADAM17). As well, inflammatory signaling in EAC promotes the expression of furin with further propagation of malignant transformation. CONCLUSION: Furin is associated with the development and progression of EAC through the induction of proliferation, invasion, and metastasis of malignant cells of EAC. Furin induces ontogenesis in EAC through activation expression of ADAM17, pro-renin receptor, CD109, and TGF-ß. As well, EAC-mediated inflammation promotes the expression of furin with further propagation of neoplastic growth and invasion.

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.

Discussing pathologic mechanisms of Diabetic retinopathy & therapeutic potentials of curcumin and ß-glucogallin in the management of Diabetic retinopathy.

Diabetic retinopathy (DR) is a form of retinal microangiopathy that occurs as a result of long-term Diabetes mellitus (DM). Patients with Diabetes mellitus typically suffer from DR as a progression of the disease that may be due to initiation and dysregulation of pathways like the polyol, hexosamine, the AGE/RAGE, and the PKC pathway, which all have negative impacts on eye health and vision. In this review, various databases, including PubMed, Google Scholar, Web of Science, and Science Direct, were scoured for data relevant to the aforementioned title. The three most common therapies for DR today are retinal photocoagulation, anti-vascular endothelial growth factor (VEGF) therapy, and vitrectomy, however, there are a number of drawbacks and limits to these methods. So, it is of critical importance and profound interest to discover treatments that may successfully address the pathogenesis of DR. Curcumin and ß-glucogallin are the two potent compounds of natural origin that are already being used in various nutraceutical formulations for several ailments. They have been shown potent antiapoptotic, anti-inflammatory, antioxidant, anticancer, and pro-vascular function benefits in animal experiments. Their parent plant species have been used for generations by practitioners of traditional herbal medicine for the treatment and prevention of various eye ailments. In this review, we will discuss about pathophysiology of Diabetic retinopathy and the therapeutic potentials of curcumin and ß-glucogallin one of the principal compounds from Curcuma longa and Emblica officinalis in Diabetic retinopathy.

Therapeutic potential of Lawsonia inermis Linn: a comprehensive overview.

Lawsonia inermis Linn, commonly known as henna, is a member of the Lythraceae family and has been found to contain a variety of compounds with both industrial and medicinal applications in its stem, bark, roots, flowers, and seeds. This report provides a comprehensive review of the bioactive components, pharmacological activities, pharmacokinetics, and pharmacological side effects of Lawsonia inermis. Relevant materials were gathered from Google Scholar, PubMed, Scopus, and Web of Science and reviewed for important properties and updates about the plant. Lawsonia inermis contains a variety of bioactive compounds, including flavonoids, coumarins, triterpenoids, steroids, xanthones, polyphenols, fatty acids, alkaloids, quinones, tannins, leucocyandin, epicatechin, catechin, and quercetin. The plant is been traditionally used to treat numerous conditions, including ulcers, bronchitis, lumbago, hemicrania, leukoderma, scabies, boils, ophthalmic disorders, hair loss, and jaundice. It has also been found to possess a range of pharmacological activities, including antioxidant, anti-inflammatory, analgesic, antiparasitic, hepatoprotective, antifungal, antitumor, wound healing, and hypoglycemic effects. The potential of Lawsonia inermis for various biological applications is promising, and further studies are needed to fully explore its therapeutic benefits for various diseases of public health. Concern advances in drug development could enable the characterization of various bioactive constituents and facilitate their development and application for the benefit of humanity.

A Systematic Review of Phytochemistry, Nutritional Composition, and Pharmacologic Application of Species of the Genus Viola in Noncommunicable Diseases (NCDs).

Viola L. is the largest genus of the Violaceae family with more than 500 species across the globe. The present extensive literature survey revealed Viola species to be a group of important nutritional and medicinal plants used for the ethnomedicinal treatment of noncommunicable diseases (NCDs) such as diabetes, asthma, lung diseases, and fatigue. Many plant species of this genus have also received scientific validation of their pharmacological activities including neuroprotective, immunomodulatory, anticancer, antihypertensive, antidyslipidemic, analgesic, antipyretic, diuretic, anti-inflammatory, anthelmintic, and antioxidant. Viola is highly rich in different natural products some of which have been isolated and identified in the past few decades; these include flavonoids terpenoids and phenylpropanoids of different pharmacological activities. The pharmacokinetics and clinical studies on this genus are lacking, and the present review is aimed at summarizing the current understanding of the ethnopharmacology, phytochemistry, nutritional composition, and pharmacological profile of medicinal plants from the Viola genus to reveal its therapeutic potentials, gaps, and subsequently open a new window for future pharmacological research.

New insights on the potential effect of progesterone in Covid-19: Anti-inflammatory and immunosuppressive effects.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic disease caused by severe acute respiratory syndrome CoV type 2 (SARS-CoV-2). COVID-19 is higher in men than women and sex hormones have immune-modulator effects during different viral infections, including SARS-CoV-2 infection. One of the essential sex hormones is progesterone (P4). AIMS: This review aimed to reveal the association between P4 and Covid-19. RESULTS AND DISCUSSION: The possible role of P4 in COVID-19 could be beneficial through the modulation of inflammatory signaling pathways, induction of the release of anti-inflammatory cytokines, and inhibition release of pro-inflammatory cytokines. P4 stimulates skew of naïve T cells from inflammatory Th1 toward anti-inflammatory Th2 with activation release of anti-inflammatory cytokines, and activation of regulatory T cells (Treg) with decreased interferon-gamma production that increased during SARS-CoV-2 infection. In addition, P4 is regarded as a potent antagonist of mineralocorticoid receptor (MR), it could reduce MRs that were activated by stimulated aldosterone from high AngII during SARS-CoV-2. P4 active metabolite allopregnanolone is regarded as a neurosteroid that acts as a positive modulator of γ-aminobutyric acid (GABAA ) so it may reduce neuropsychiatric manifestations and dysautonomia in COVID-19 patients. CONCLUSION: Taken together, the anti-inflammatory and immunomodulatory properties of P4 may improve central and peripheral complications in COVID-19.

Melatonin as a promising therapeutic intervention for restoring ovarian function in letrozole-induced polycystic ovary syndrome rats.

Polycystic ovary syndrome (PCOS) is a common hormonal disorder that affects women of reproductive age and is characterized by multiple ovarian cysts, irregular menstrual cycles, and excessive androgen hormone production. The present study aimed to investigate the therapeutic efficacy of melatonin in alleviating PCOS-induced alterations in female Wistar rats. PCOS was induced in female albino rats by administering letrozole at a dose of 1 mg/kg for 21 days. A total of 24 rats were randomly selected and divided into four groups: group I (normal control), group II (melatonin treatment), group III (letrozole treatment), and group IV (melatonin therapy for PCOS rats). Physical parameters (body and uterus weight), hormone profile (LH and FSH), and steroidogenic enzyme activities and an oral glucose test were assessed using standard methods. Histological analysis was performed using hematoxylin and eosin staining. The results demonstrated that exogenous melatonin administration significantly improved PCOS symptoms in rats, including reduced body weight gain, changes in organ weight/body weight index, blood glucose level, percentage diestrus phase, testosterone, estradiol, progesterone, and LH/FSH ratio, as well as 3ß-HSD and 17ß-HSD enzyme activity. Histopathological findings revealed well-developed follicles, decreased cystic follicles, and increased antral follicles, Graafian follicles, and corpus luteum in PCOS rats treated with melatonin. These positive outcomes suggest that exogenous melatonin may hold promise as a valuable remedy for PCOS conditions in female rats. Further research is warranted to fully elucidate the underlying mechanisms and potential clinical applications of melatonin in the context of PCOS.

New insights on the potential anti-epileptic effect of metformin: Mechanistic pathway.

Epilepsy is a chronic neurological disease characterized by recurrent seizures. Epilepsy is observed as a well-controlled disease by anti-epileptic agents (AEAs) in about 69%. However, 30%-40% of epileptic patients fail to respond to conventional AEAs leading to an increase in the risk of brain structural injury and mortality. Therefore, adding some FDA-approved drugs that have an anti-seizure activity to the anti-epileptic regimen is logical. The anti-diabetic agent metformin has anti-seizure activity. Nevertheless, the underlying mechanism of the anti-seizure activity of metformin was not entirely clarified. Henceforward, the objective of this review was to exemplify the mechanistic role of metformin in epilepsy. Metformin has anti-seizure activity by triggering adenosine monophosphate-activated protein kinase (AMPK) signalling and inhibiting the mechanistic target of rapamycin (mTOR) pathways which are dysregulated in epilepsy. In addition, metformin improves the expression of brain-derived neurotrophic factor (BDNF) which has a neuroprotective effect. Hence, metformin via induction of BDNF can reduce seizure progression and severity. Consequently, increasing neuronal progranulin by metformin may explain the anti-seizure mechanism of metformin. Also, metformin reduces α-synuclein and increases protein phosphatase 2A (PPA2) with modulation of neuroinflammation. In conclusion, metformin might be an adjuvant with AEAs in the management of refractory epilepsy. Preclinical and clinical studies are warranted in this regard.

Addressing cancer care inequities in sub-Saharan Africa: current challenges and proposed solutions.

INTRODUCTION: Cancer is a significant public health challenge globally, with nearly 2000 lives lost daily in Africa alone. Without adequate measures, mortality rates are likely to increase. The major challenge for cancer care in Africa is equity and prioritization, as cancer is not receiving adequate attention from policy-makers and strategic stakeholders in the healthcare space. This neglect is affecting the three primary tiers of cancer care: prevention, diagnosis, and treatment/management. To promote cancer care equity, addressing issues of equity and prioritization is crucial to ensure that everyone has an equal chance at cancer prevention, early detection, and appropriate care and follow-up treatment. METHODOLOGY: Using available literature, we provide an overview of the current state of cancer care in Africa and recommendations to close the gap. RESULTS: We highlight several factors that contribute to cancer care inequity in Africa, including inadequate funding for cancer research, poor cancer education or awareness, inadequate screening or diagnostic facilities, lack of a well-organized and effective cancer registry system and access to care, shortage of specialized medical staff, high costs for screening, vaccination, and treatment, lack of technical capacity, poor vaccination response, and/or late presentation of patients for cancer screening. We also provide recommendations to address some of these obstacles to achieving cancer care equity. Our recommendations are divided into national-level initiatives and capacity-based initiatives, including cancer health promotion and awareness by healthcare professionals during every hospital visit, encouraging screening and vaccine uptake, ensuring operational regional and national cancer registries, improving healthcare budgeting for staff, equipment, and facilities, building expertise through specialty training, funding for cancer research, providing insurance coverage for cancer care, and implementing mobile health technology for telemedicine diagnosis. CONCLUSION: Addressing challenges to cancer equity holistically would improve the likelihood of longer survival for cancer patients, lower the risk factors for groups that are already at risk, and ensure equitable access to cancer care on the continent. This study identifies the existing stance that African nations have on equity in cancer care, outlines the current constraints, and provides suggestions that could make the biggest difference in attaining equity in cancer care.

Nanotechnology-Based Drug Delivery Approaches of Mangiferin: Promises, Reality and Challenges in Cancer Chemotherapy.

Mangiferin (MGF), a xanthone derived from Mangifera indica L., initially employed as a nutraceutical, is now being explored extensively for its anticancer potential. Scientists across the globe have explored this bioactive for managing a variety of cancers using validated in vitro and in vivo models. The in vitro anticancer potential of this biomolecule on well-established breast cancer cell lines such as MDA-MB-23, BEAS-2B cells and MCF-7 is closer to many approved synthetic anticancer agents. However, the solubility and bioavailability of this xanthone are the main challenges, and its oral bioavailability is reported to be less than 2%, and its aqueous solubility is also 0.111 mg/mL. Nano-drug delivery systems have attempted to deliver the drugs at the desired site at a desired rate in desired amounts. Many researchers have explored various nanotechnology-based approaches to provide effective and safe delivery of mangiferin for cancer therapy. Nanoparticles were used as carriers to encapsulate mangiferin, protecting it from degradation and facilitating its delivery to cancer cells. They have attempted to enhance the bioavailability, safety and efficacy of this very bioactive using drug delivery approaches. The present review focuses on the origin and structure elucidation of mangiferin and its derivatives and the benefits of this bioactive. The review also offers insight into the delivery-related challenges of mangiferin and its applications in nanosized forms against cancer. The use of a relatively new deep-learning approach to solve the pharmacokinetic issues of this bioactive has also been discussed. The review also critically analyzes the future hope for mangiferin as a therapeutic agent for cancer management.

The potential link between acromegaly and risk of acute ischemic stroke in patients with pituitary adenoma: a new perspective.

Acromegaly is an endocrine disorder due to the excess production of growth hormone (GH) from the anterior pituitary gland after closed epiphyseal growth plates. Acromegaly is mainly caused by benign GH-secreting pituitary adenoma. Acute ischemic stroke (AIS) is one of the most common cardiovascular complications. It ranks second after ischemic heart disease (IHD) as a cause of disability and death in high-income countries globally. Thus, this review aimed to elucidate the possible link between acromegaly and the development of AIS. The local effects of acromegaly in the development of AIS are related to the development of pituitary adenoma and associated surgical and radiotherapies. Pituitary adenoma triggers the development of AIS through different mechanisms, particularly aneurysmal formation, associated thrombosis, and alteration of cerebral microcirculation. Cardiovascular complications and mortality were higher in patients with pituitary adenoma. The systemic effect of acromegaly-induced cardio-metabolic disorders may increase the risk for the development of AIS. Additionally, acromegaly contributes to the development of endothelial dysfunction (ED), inflammatory and oxidative stress, and induction of thrombosis that increases the risk for the development of AIS. Moreover, activated signaling pathways, including activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB), nod-like receptor pyrin 3 (NLRP3) inflammasome, and mitogen-activated protein kinase (MAPK) in acromegaly may induce systemic inflammation with the development of cardiovascular complications mainly AIS. Taken together, acromegaly triggers the development of AIS through local and systemic effects by inducing the formation of a cerebral vessel aneurysm, the release of pro-inflammatory cytokines, the development of oxidative stress, ED, and thrombosis correspondingly.

The potential therapeutic effect of phosphodiesterase 5 inhibitors in the acute ischemic stroke (AIS).

Acute ischemic stroke (AIS) is a focal neurological disorder that accounts for 85% of all stroke types, due to occlusion of cerebral arteries by thrombosis and emboli. AIS is also developed due to cerebral hemodynamic abnormality. AIS is associated with the development of neuroinflammation which increases the severity of AIS. Phosphodiesterase enzyme (PDEs) inhibitors have neuro-restorative and neuroprotective effects against the development of AIS through modulation of the cerebral cyclic adenosine monophosphate (cAMP)/cyclic guanosine monophosphate (cGMP)/nitric oxide (NO) pathway. PDE5 inhibitors through mitigation of neuroinflammation may decrease the risk of long-term AIS-induced complications. PDE5 inhibitors may affect the hemodynamic properties and coagulation pathway which are associated with thrombotic complications in AIS. PDE5 inhibitors reduce activation of the pro-coagulant pathway and improve the microcirculatory level in patients with hemodynamic disturbances in AIS. PDE5 inhibitors mainly tadalafil and sildenafil improve clinical outcomes in AIS patients through the regulation of cerebral perfusion and cerebral blood flow (CBF). PDE5 inhibitors reduced thrombomodulin, P-selectin, and tissue plasminogen activator. Herein, PDE5 inhibitors may reduce activation of the pro-coagulant pathway and improve the microcirculatory level in patients with hemodynamic disturbances in AIS. In conclusion, PDE5 inhibitors may have potential roles in the management of AIS through modulation of CBF, cAMP/cGMP/NO pathway, neuroinflammation, and inflammatory signaling pathways. Preclinical and clinical studies are recommended in this regard.

New insights on the potential effect of vinpocetine in Parkinson's disease: one of the neglected warden and baffling topics.

Vinpocetine (VPN) is an ethyl apovincaminate that has anti-inflammatory and antioxidant effects by inhibiting the expression of nuclear factor kappa B (NF-κB) and phosphodiesterase enzyme 1 (PDE-1). VPN is used in the management of stroke, dementia, and other neurodegenerative brain diseases. VPN may be effective in treating Parkinson's disease (PD). Therefore, this review aimed to clarify the mechanistic role of VPN in the management of PD. VPN has protective and restorative effects against neuronal injury by reducing neuroinflammation, and improvement of synaptic plasticity and cerebral blood flow. VPN protects dopaminergic neurons by reducing oxidative stress, lipid peroxidation, glutamate neurotoxicity, and regulation of Ca+ 2 overloads. VPN can alleviate PD neuropathology through its anti-inflammatory, antioxidant, antiapoptotic and neurogenic effects. VPN through inhibition of PDE1 improves cyclic adenosine monophosphate (cAMP)/cyclic guanosine monophosphate (cGMP) signaling in the dopaminergic neurons of the substantia nigra (SN). VPN improves PD neuropathology through PDE1 inhibition with a subsequent increase of the cAMP/cGMP signaling pathway. Therefore, increasing cAMP leads to antioxidant effects, while augmentation of cGMP by VPN leads to anti-inflammatory effects which reduced neurotoxicity and development of motor severity in PD. In conclusion, this review indicated that VPN could be effective in the management of PD.

Potential role of tirzepatide towards Covid-19 infection in diabetic patients: a perspective approach.

In Covid-19, variations in fasting blood glucose are considered a distinct risk element for a bad prognosis and outcome in Covid-19 patients. Tirazepatide (TZT), a dual glucagon-like peptide-1 (GLP-1)and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist may be effective in managing Covid-19-induced hyperglycemia in diabetic and non-diabetic patients. The beneficial effect of TZT in T2DM and obesity is related to direct activation of GIP and GLP-1 receptors with subsequent improvement of insulin sensitivity and reduction of body weight. TZT improves endothelial dysfunction (ED) and associated inflammatory changes through modulation of glucose homeostasis, insulin sensitivity, and pro-inflammatory biomarkers release. TZT, through activation of the GLP-1 receptor, may produce beneficial effects against Covid-19 severity since GLP-1 receptor agonists (GLP-1RAs) have anti-inflammatory and pulmoprotective implications in Covid-19. Therefore, GLP-1RAs could effectively treat severely affected Covid-19 diabetic and non-diabetic patients. Notably, using GLP-1RAs in T2DM patients prevents glucose variability, a common finding in Covid-19 patients. Therefore, GLP-1RAs like TZT could be a therapeutic strategy in T2DM patients with Covid-19 to prevent glucose variability-induced complications. In Covid-19, the inflammatory signaling pathways are highly activated, resulting in hyperinflammation. GLP-1RAs reduce inflammatory biomarkers like IL-6, CRP, and ferritin in Covid-19 patients. Therefore, GLP-1RAs like TZ may be effective in Covid-19 patients by reducing the inflammatory burden. The anti-obesogenic effect of TZT may reduce Covid-19 severity by ameliorating body weight and adiposity. Furthermore, Covid-19 may induce substantial alterations in gut microbiota. GLP-1RA preserves gut microbiota and prevents intestinal dysbiosis. Herein, TZT, like other GLP-1RA, may attenuate Covid-19-induced gut microbiota alterations and, by this mechanism, may mitigate intestinal inflammation and systemic complications in Covid-19 patients with either T2DM or obesity. As opposed to that, glucose-dependent insulinotropic polypeptide (GIP) was reduced in obese and T2DM patients. However, activation of GIP-1R by TZT in T2DM patients improves glucose homeostasis. Thus, TZT, through activation of both GIP and GLP-1, may reduce obesity-mediated inflammation. In Covid-19, GIP response to the meal is impaired, leading to postprandial hyperglycemia and abnormal glucose homeostasis. Therefore, using TZT in severely affected Covid-19 patients may prevent the development of glucose variability and hyperglycemia-induced oxidative stress. Moreover, exaggerated inflammatory disorders in Covid-19 due to the release of pro-inflammatory cytokines like IL-1ß, IL-6, and TNF-α may lead to systemic inflammation and cytokine storm development. Besides, GIP-1 inhibits expression of IL-1ß, IL-6, MCP-1, chemokines and TNF-α. Therefore, using GIP-1RA like TZT may inhibit the onset of inflammatory disorders in severely affected Covid-19 patients. In conclusion, TZT, through activation of GLP-1 and GIP receptors, may prevent SARS-CoV-2-induced hyperinflammation and glucose variability in diabetic and non-diabetic patients.