Empagliflozin protective effects against cisplatin-induced acute nephrotoxicity by interfering with oxidative stress and inflammation in Wistar rats.

Cisplatin (Cis) is a platinum-based antineoplastic drug used in various types of cancers. This drug can induce nephrotoxicity as a cause of acute kidney injury (AKI) by inducing oxidative stress and inflammation. Empagliflozin (Empa) is a newly developed inhibitor of sodium-glucose cotransporter-2 (SGLT2) approved as an antidiabetic medication for patients with type 2 diabetes mellitus. In addition to its blood glucose-lowering effect, Empa has been shown to exert anti-inflammatory and anti-oxidant properties. The current study aimed to investigate the protective effects of Empa on Cis-induced nephrotoxicity in rats. Male Wistar albino rats were divided into five groups, each of six rats: Sham group (received vehicle for 7 days), Control group (received vehicle for 7 days and Cis injection on day 2), Cis + Empa10 (received 10mg/kg Empa for 7 days and Cis injection on day 2), Cis + Empa30 (received 30mg/kg Empa for 7 days and Cis injection on day 2) and, Empa 30 (received 30mg/kg Empa for 7 days). One day after the last injection in each group, rats were weighed and then sacrificed to analyze the hematological, biochemical, and histological parameters. Cis markedly increased levels of inflammatory parameters such as renal tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and myeloperoxidase (MPO) activity. Notably, malondialdehyde (MDA), blood urea nitrogen (BUN), and creatinine levels were enhanced after Cis administration. Also, the chemotherapeutic agent significantly reduced antioxidant indicators such as renal catalase (CAT), glutathione peroxidase (GpX), and superoxide dismutase (SOD). Furthermore, histopathological examinations also revealed severe renal damage following Cis treatment which was improved by Empa administration. Empa treatment at both doses (10 mg/kg and 30 mg/kg) reversed Cis-induced changes in all the above renal parameters. In conclusion, Empa has protective effects on Cis-induced nephrotoxicity by inhibition of oxidative stress and inflammation.

Sex-controlled differences in sertraline and citalopram efficacies in major depressive disorder: a randomized, double-blind trial.

To investigate the response to antidepressants while controlling for sex, which has been controversial, 92 outpatient males and females with major depressive disorder were assigned to sertraline (100 mg/day) or citalopram (40 mg/day) in two strata and were assessed using Hamilton depression rating scale (HDRS) scores and brain-derived neurotrophic factor (BDNF), interleukin (IL)-6 and cortisol serum levels in this 8-week, randomized, parallel-group, double-blind clinical trial. Data of 40 sertraline and 40 citalopram recipients with equal representation of males and females assigned to each medication were analyzed, while their baseline characteristics were not statistically different (P > 0.05). There were no significant differences between sertraline and citalopram recipients in outcome changes (P > 0.05), all of which indicated improvement, but a significant time-treatment-sex interaction effect in BDNF levels was observed (P = 0.035). Regarding this, subgroup analyses illustrated a significantly greater increase in male BDNF levels following sertraline treatment (P = 0.020) with a moderate to large effect size (Cohen's d = 0.76 and ). Significant associations were observed between percentage changes in IL-6 levels and BDNF levels in sertraline recipients (P = 0.033) and HDRS scores in citalopram recipients (P < 0.001). Sex was an effect modifier in BDNF alterations following sertraline and citalopram administration. Further large-scale, high-quality, long-term studies are recommended.

Protective Effects of Plant-Derived Compounds Against Traumatic Brain Injury.

Inflammation in the nervous system is one of the key features of many neurodegenerative diseases. It is increasingly being identified as a critical pathophysiological primitive mechanism associated with chronic neurodegenerative diseases following traumatic brain injury (TBI). Phytochemicals have a wide range of clinical properties due to their antioxidant and anti-inflammatory effects. Currently, there are few drugs available for the treatment of neurodegenerative diseases other than symptomatic relief. Numerous studies have shown that plant-derived compounds, in particular polyphenols, protect against various neurodegenerative diseases and are safe for consumption. Polyphenols exert protective effects on TBI via restoration of nuclear factor kappa B (NF-κB), toll-like receptor-4 (TLR4), and Nod-like receptor family proteins (NLRPs) pathways. In addition, these phytochemicals and their derivatives upregulate the phosphatidylinositol-3-Kinase/Protein Kinase B (PI3K/AKT) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, which have critical functions in modulating TBI symptoms. There is supporting evidence that medicinal plants and phytochemicals are protective in different TBI models, though future clinical trials are needed to clarify the precise mechanisms and functions of different polyphenolic compounds in TBI.

Therapeutic effects of anti-diabetic drugs on traumatic brain injury.

AIMS: In this narrative review, we have analyzed and synthesized current studies relating to the effects of anti-diabetic drugs on traumatic brain injury (TBI) complications. METHODS: Eligible studies were collected from Scopus, Google Scholar, PubMed, and Cochrane Library for clinical, in-vivo, and in-vitro studies published on the impact of anti-diabetic drugs on TBI. RESULTS: Traumatic brain injury (TBI) is a serious brain disease that is caused by any type of trauma. The pathophysiology of TBI is not yet fully understood, though physical injury and inflammatory events have been implicated in TBI progression. Several signaling pathways are known to play pivotal roles in TBI injuries, including Nuclear factor erythroid 2-related factor 2 (Nrf2), High mobility group box 1 protein/Nuclear factor kappa B (HMGB1/NF-κB), Adiponectin, Mammalian Target of Rapamycin (mTOR), Toll-Like Receptor (TLR), Wnt/ß-catenin, Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT), Nod-like receptor protein3 (NLRP3) inflammasome, Phosphoglycerate kinase 1/Kelch-like ECH-associated protein 1 (PGK1/KEAP1)/Nrf2, and Mitogen-activated protein kinase (MAPK) . Recent studies suggest that oral anti-diabetic drugs such as biguanides, thiazolidinediones (TZDs), sulfonylureas (SUs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), dipeptidyl peptidase-4 inhibitors (DPPIs), meglitinides, and alpha-glucosidase inhibitors (AGIs) could have beneficial effects in the management of TBI complications. These drugs may downregulate the inflammatory pathways and induce antioxidant signaling pathways, thus alleviating complications of TBI. CONCLUSION: Based on this comprehensive literature review, antidiabetic medications might be considered in the TBI treatment protocol. However, evidence from clinical trials in patients with TBI is still warranted.

Cinnamic Acid Ameliorates Acetic Acid-induced Inflammatory Response through Inhibition of TLR-4 in Colitis Rat Model.

BACKGROUND: Cinnamic acid, an active compound in cinnamon spp., has anti-inflamatory and antioxidant characteristics and is favorable in managing inflammatory bowel diseases. OBJECTIVE: Evaluate cinnamic acid's effects on colitis in rats. METHODS: To induce colitis in experimental rats, excluding the sham group, a 4% intrarectal solution of acetic acid was administered. The rats were then given oral doses of cinnamic acid at 30, 45, and 90 mg/kg for two days. The animals were assessed for macroscopic and microscopic changes, and the levels of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) were measured using Eliza kits. Additionally, real-time PCR was performed to examine the gene level of toll-like receptor 4 (TLR-4) in the colon. RESULTS: Effective reduction of inflammation in acetic acid-induced colitis was achieved through cinnamic acid at doses of 45 and 90 mg/kg. The decrease was achieved by inhibiting the activities of TNF-α, IL-6, and MPO while downregulating the expression of TLR-4. It is important to note that macroscopic and microscopic evaluations were significant in determining the effectiveness of cinnamic acid in reducing inflammation. CONCLUSION: Downregulation of inflammatory cytokines and TLR-4 expression may contribute to cinnamic acid's anti-inflammatory effect.

Monophosphoryl lipid A as a co-adjuvant in methicillin-resistant Staphylococcus aureus vaccine development: improvement of immune responses in a mouse model of infection.

To increase the effectiveness of methicillin-resistant Staphylococcus aureus vaccines (MRSA), a new generation of immune system stimulating adjuvants is necessary, along with other adjuvants. In some vaccines, monophosphoryl lipid A (MPLA) as a toll-like receptor 4 agonist is currently used as an adjuvant or co-adjuvant. MPLA could increase the immune response and vaccine immunogenicity. The current investigation assessed the immunogenicity and anti-MRSA efficacy of recombinant autolysin formulated in MPLA and Alum as co-adjuvant/adjuvant. r-Autolysin was expressed and purified by Ni-NTA affinity chromatography and characterized by SDS-PAGE. Then, the vaccine candidate formulation in MPLAs and Alum was prepared. To investigate the immunogenic responses, total IgG, isotype (IgG1 and IgG2a) levels, and cytokines (IL-4, IL-12, TNF-α, and IFN-γ) profiles were evaluated by ELISA. Also, the bacterial burden in internal organs, opsonophagocytosis, survival rate, and pathobiology changes was compared among the groups. Results demonstrated that mice immunized with the r-Autolysin + Alum + MPLA Synthetic and r-Autolysin + Alum + MPLA Biologic led to increased levels of opsonic antibodies, IgG1, IgG2a isotype as well as increased levels of cytokines profiles, as compared with other experimental groups. More importantly, mice immunized with MPLA and r-Autolysin exhibited a decrease in mortality and bacterial burden, as compared with the control group. The highest level of survival was seen in the r-Autolysin + Alum + MPLA Synthetic group. We concluded that both MPLA forms, synthetic and biological, are reliable candidates for immune response improvement against MRSA infection.

LRRK2; Communicative Role in the Treatment of Parkinson's Disease and Ulcerative Colitis Overlapping.

BACKGROUND: Involvement of gastrointestinal inflammation in Parkinson's disease (PD) pathogenesis and movement have progressively emerged. Inflammation is involved in the etiology of both PD and inflammatory bowel disease (IBD). Transformations in leucine-rich recurrent kinase 2 (LRRK2) are among the best hereditary supporters of IBD and PD. Elevated levels of LRRK2 have been reported in stimulated colonic tissue from IBD patients and peripheral invulnerable cells from irregular PD patients; thus, it is thought that LRRK2 directs inflammatory cycles. OBJECTIVE: Since its revelation, LRRK2 has been seriously linked in neurons, albeit various lines of proof affirmed that LRRK2 is profoundly communicated in invulnerable cells. Subsequently, LRRK2 might sit at a junction by which stomach inflammation and higher LRRK2 levels in IBD might be a biomarker of expanded risk for inconsistent PD or potentially may address a manageable helpful objective in incendiary sicknesses that increment the risk of PD. Here, we discuss how PD and IBD share covering aggregates, especially regarding LRRK2 and present inhibitors, which could be a helpful objective in ongoing treatments. METHOD: English data were obtained from Google Scholar, PubMed, Scopus, and Cochrane library studies published between 1990-December 2022. RESULT: Inhibitors of the LRRK2 pathway can be considered as the novel treatment approaches for IBD and PD treatment. CONCLUSION: Common mediators and pathways are involved in the pathophysiology of IBD and PD, which are majorly correlated with inflammatory situations. Such diseases could be used for further clinical investigations.

Systematic Review on Herbal Preparations for Controlling Visceral Hypersensitivity in Functional Gastrointestinal Disorders.

BACKGROUND: Visceral hypersensitivity (VH) is an overreaction of the gastrointestinal (GI) tract to various stimuli and is characterized by hyperalgesia and/or allodynia. VH contributes to the etiology of many GI dysfunctions, particularly irritable bowel syndrome (IBS). Although the exact mechanisms underlying VH are yet to be found, inflammation and oxidative stress, psychosocial factors, and sensorimotor alterations may play significant roles in it. OBJECTIVE: In this review, we provide an overview of VH and its pathophysiological function in GI disorders. Adverse effects of synthetic drugs may make herbal agents a good candidate for pain management. Therefore, in this review, we will discuss the efficacy of herbal agents in the management of VH with a focus on their anti-inflammatory and antioxidant potentials. METHODS: Data were extracted from clinical and animal studies published in English between 2004 and June, 2020, which were collected from PubMed, Google Scholar, Scopus, and Cochrane Library. RESULTS: Overall, Radix, Melissia, Glycyrrhizae, Mentha, and Liquorice were the most efficient herbals for VH management in IBS and dyspepsia, predominantly through modulation of the mRNA expression of transient receptor potential vanilloid type-1 (TRPV1) and suppression of 5- hydroxytryptamine 3 (5-HT3) or the serotonin receptors. CONCLUSION: Considering the positive effects of herbal formulations in VH management, further research on novel herbal and/or herbal/chemical preparations is warranted.

Spinal Muscular Atrophy Treatment: The MTOR Regulatory Intervention.

Spinal muscular atrophy (SMA) is a hereditary disorder affecting neurons and muscles, resulting in muscle weakness and atrophy. Most SMA cases are diagnosed during infancy or early childhood, the most common inherited cause of infant mortality without treatment. Still, SMA might appear at older ages with milder symptoms. SMA patients demonstrate progressive muscle waste, movement problems, tremors, dysphagia, bone and joint deformations, and breathing difficulties. The mammalian target of rapamycin (mTOR), the mechanistic target of rapamycin, is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases encoded by the mTOR gene in humans. The mTOR phosphorylation, deregulation, and autophagy have shown dissimilarity amongst SMA cell types. Therefore, exploring the underlying molecular process in SMA therapy could provide novel insights and pave the way for finding new treatment options. This paper provides new insight into the possible modulatory effect of mTOR/ autophagy in SMA management.

Superoxide dismutase: a key target for the neuroprotective effects of curcumin.

Over the past few years, the prevalence of neurodegenerative diseases (NDD) has increased dramatically. The community health system is burdened by the high healthcare costs associated with NDD. Superoxide dismutase (SOD) is a type of metalloenzyme that possesses a distinct characteristic of protecting the body from oxidative stress through antioxidants. In this way, SOD supplementation may activate the endogenous antioxidant mechanism in various pathological conditions and could be used to neutralize free radical excess. Several factors are responsible for damaging DNA and RNA in the body, including the overproduction of reactive species, particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS). Excessive ROS/RNS have deleterious effects on mitochondria and their metabolic processes, mainly through increased mitochondrial proteins, lipids and DNA oxidation. Studies have shown that oxidative stress is implicated in the etiology of many diseases, including NDD. It is thought that anti-inflammatory compounds, particularly phytochemicals, can interfere with these pathways and regulate inflammation. Extensive experimental and clinical research has proven that curcumin (Cur) has anti-inflammatory and anti-neurologic properties. In this review, we have compiled the available data on Cur's anti-inflammatory properties, paying special attention to its therapeutic impact on NDD through SOD.

The time interval between injection of nicotine and tremor initiation: a new index for evaluating nicotine efficacy in rodents.

Tremor is one of the effects of nicotine as a toxic substance, especially in animal models. The intensity and duration of tremors were used to evaluate the effect of nicotine on locomotor activity in laboratory animals. In our observations, the time interval between nicotine injection and the onset of tremor changed depending on the dose. Therefore, by increasing the dose of nicotine in rats, the time interval of tremor onset was also shortened. These results suggest that the time interval between nicotine injection and the onset of tremors can be used as a complementary index for better evaluation of nicotine-derived motor disturbances.

Therapeutic approaches for cholestatic liver diseases: the role of nitric oxide pathway.

Cholestasis describes bile secretion or flow impairment, which is clinically manifested with fatigue, pruritus, and jaundice. Neutrophils play a crucial role in many diseases such as cholestasis liver diseases through mediating several oxidative and inflammatory pathways. Data have been collected from clinical, in vitro, and in vivo studies published between 2000 and December 2021 in English and obtained from the PubMed, Google Scholar, Scopus, and Cochrane libraries. Although nitric oxide plays an important role in the pathogenesis of cholestatic liver diseases, excessive levels of NO in serum and affected tissues, mainly synthesized by the inducible nitric oxide synthase (iNOS) enzyme, can exacerbate inflammation. NO induces the inflammatory and oxidative processes, which finally leads to cell damage. We found that natural products such as baicalin, curcumin, resveratrol, and lycopene, as well as chemical likes ursodeoxycholic acid, dexamethasone, rosuvastatin, melatonin, and sildenafil, are able to markedly attenuate the NO production and iNOS expression, mainly through inducing the nuclear factor κB (NF-κB), Janus kinase and signal transducer and activator of transcription (JAK/STAT), and toll like receptor-4 (TLR4) signaling pathways. This study summarizes the latest scientific data about the bile acid signaling pathway, the neutrophil chemotaxis recruitment process during cholestasis, and the role of NO in cholestasis liver diseases. Literature review directed us to propose that suppression of NO and its related pathways could be a therapeutic option for preventing or treating cholestatic liver diseases.

TLR/mTOR inflammatory signaling pathway: novel insight for the treatment of schizophrenia.

The Toll-like receptor (TLR)/mammalian target of rapamycin (mTOR) signaling pathway is involved in the intracellular regulation of protein synthesis, specifically the ones that mediate neuronal morphology and facilitate synaptic plasticity. The activity of TLR/mTOR signaling has been disrupted, leading to neurodevelopment and deficient synaptic plasticity, which are the main symptoms of schizophrenia. The TLR receptor activates the mTOR signaling pathway and increases the elevation of inflammatory cytokines. Interleukin (IL)-6 is the most commonly altered cytokine, while IL-1, tumor necrosis factor, and interferon (IFN) also lead to SCZ. Anti-inflammatory and anti-oxidative agents such as celecoxib, aspirin, minocycline, and omega-3 fatty acids have shown efficiency against SCZ. As a result, inhibition of the inflammatory process could be suggested for the treatment of SCZ. So mTOR/TLR blockers represent the treatment of SCZ due to their inflammatory consequences. The objective of the present work was to find a novel anti-inflammatory agent that may block the mTOR/TLR inflammatory signaling pathways and might pave the way for the treatment of neuroinflammatory SCZ. Data were collected from experimental and clinical studies published in English between 1998 and October 2022 from Google Scholar, PubMed, Scopus, and the Cochrane library.

Juglone Mediates Inflammatory Bowel Disease Through Inhibition of TLR-4/NF KappaB Pathway in Acetic Acid-induced Colitis in Rats.

BACKGROUND: Juglone is a phenolic bioactive compound with antimicrobial, antitumour, antioxidant, and anti-inflammatory characteristics. Given its anti-inflammatory and antioxidant effects, it was selected for evaluation in the inflammatory bowel diseases (IBD) model. OBJECTIVE: The current study was performed to evaluate the therapeutic impacts of the juglone in acetic acid-induced colitis in male Wistar rats. METHODS: Juglone was extracted from Pterocarya fraxinifolia via maceration method. Colitis was induced in 36 male Wistar rats (n = 6), except in the sham group, 1 ml of acetic acid 4% was administered intrarectally. Twenty-four hours after induction of colitis, in 3 groups, juglone was administered orally (gavage) at 3 doses of 50, 100, and 150 mg/kg for 2 successive days (once a day). Other groups included the control group (only treated with acetic acid), sham group (normal saline), and standard group (Dexamethasone). To evaluate the inflammation sites, macroscopic and microscopic markers were assessed. The mRNA expression of interleukin (IL)-1ß, and tumor necrosis factor-alpha (TNF)-α were assessed by real-time PCR, while myeloperoxidase (MPO) was measured spectrophotometrically. ELISA assay kits were used to determine the colonic levels of SOD, ROS, NF-κB, and TLR-4. RESULTS: Macroscopic and microscopic assessments revealed that juglone significantly decreased colonic tissue damage and inflammation at 150 mg/kg. Juglone at 100, 150 mg/kg significantly decreased the TNF-α, MPO, and TLR-4 levels, as well as the SOD activity. All juglone-treated groups reduced the NF-κB levels compared to the control group (p < 0.001). The compound decreased the IL-1ß, and ROS levels at the concentration of 150 mg/kg. Juglone attenuated colitis symptoms, reduced inflammation cytokines, declined neutrophil infiltration, and suppressed IL- 1ß and TNF-α expressions in acetic acid-induced colitis rats. It may be proposed that juglone improved colitis in animal model through suppression of inflammatory parameters and downregulation of the NF-κB-TLR-4 pathway. CONCLUSION: Juglone exhibited anti-inflammatory and antioxidant effects in the experimental colitis model and could be a therapeutic candidate for IBD. Juglone should be a subject for further animal and clinical trials in IBD models and for safety concerns.

An Overview of the Pharmacological Properties of Calebin-A.

The natural polyphenol, calebin-A, was recently discovered and identified as a novel phytopharmaceutical with anti-inflammatory, anti-tumor, and antiproliferative properties. Calebin-A occurs naturally in trace quantities in Curcuma longa/C cassia, commonly known as turmeric, from the Zingiberaceae family. Calebin-A is a curcumin analog or 'chemical cousin' of curcumin with a similar chemical structure. Although few research studies have been conducted on the pharmacological and therapeutic properties of calebin-A, it is a very promising molecule with a variety of pharmacological properties. Some studies have suggested that calebin-A is helpful in treating various cancers due to its inhibitory effect on cell growth and anti-inflammatory properties. Other studies have suggested that calebin-A may improve neurocognitive status associated with neurodegeneration caused by Alzheimer's disease (AD) by inhibiting the aggregation of ß-amyloid. Finally, several studies have proposed that calebin-A may potentially be therapeutically beneficial in treating patients with obesity. This novel compound downregulates nuclear factor (NF)-κB-mediated processes involved with cancer, such as tumor cell invasion, proliferation, metastasis, and, most profoundly, inflammation. Moreover, calebin-A influences the activities of mitogen-activated protein kinases (MAPKs) in cancer cells. The present review identifies and discusses the pharmacological and phytochemical properties of calebin-A, as well as its therapeutic benefits and limitations, for future scientists and clinicians interested in exploring calebin-A's medicinal qualities.

Sodium Glucose Transporter-2 Inhibitors (SGLT2Is)-TLRs Axis Modulates Diabetes.

Diabetes affects millions of people worldwide and is mainly associated with impaired insulin function. To date, various oral anti-diabetic drugs have been developed, of which, the sodium glucose transporter-2 inhibitors (SGLT2Is) are of the most recent classes that have been introduced. They differ from other classes in terms of their novel mechanism of actions and unique beneficial effects rather than just lowering glucose levels. SGLT2Is can protect body against cardiovascular events and kidney diseases even in non-diabetic individuals. SGLT2Is participate in immune cell activation, oxidative stress reduction, and inflammation mediation, thereby, moderating diabetic complications. In addition, toll like receptors (TLRs) are the intermediators of the immune system and inflammatory process, thus it's believed to play crucial roles in diabetic complications, particularly the ones that are related to inflammatory reactions. SGLT2Is are also effective against diabetic complications via their anti-inflammatory and oxidative properties. Given the anti-inflammatory properties of TLRs and SGLT2Is, this review investigates how SGLT2Is can affect the TLR pathway, and whether this could be favorable toward diabetes.

Pharmacological activities of turmerones.

Turmerones are major bioactive compounds of Curcuma species with several beneficial pharmacological activities. In addition, various in vivo and in vitro studies noted that turmerones could affect different cytokines, metabolic pathways, and targets. Turmerones will have the potential to be a candidate agent to lessen many pathological and immunological conditions as a result of these pharmacological activities. In this review, we provided information about the pharmacological actions of turmerones using search engines such as PubMed, Google Scholar, Scopus, and Web of Science.

Impact of curcumin on p38 MAPK: therapeutic implications.

Curcumin (diferuloylmethane) is a herbal remedy which possesses numerous biological attributes including anti-inflammatory, anti-oxidant and anti-cancer properties. Curcumin has been shown to impact a number of signaling pathways including nuclear factor kappa B (NF-KB), reactive oxygen species (ROS), Wingless/Integrated (Wnt), Janus kinase-signal transducer and activator of mitogen-activated protein kinase (MAPK) and transcription (JAK/STAT). P38 belongs to the MAPKs, is known as a stress-activated MAPK and is involved in diverse biological responses. P38 is activated in various signaling cascades. P38 plays a role in inflammation, cell differentiation, proliferation, motility and survival. This cascade can serve as a therapeutic target in many disorders. Extensive evidence confirms that curcumin impacts the P38 MAPK signaling pathway, through which it exerts anti-inflammatory, neuroprotective, and apoptotic effects. Hence, curcumin can positively affect inflammatory disorders and cancers, as well as to increase glucose uptake in cells. This review discusses the pharmacological and therapeutic effects of curcumin as effected through p38 MAPK.

The Relationship Between Psoriasis, COVID-19 Infection and Vaccination During Treatment of Patients.

Since the outbreak of the COVID-19 pandemic in December 2019, scientists worldwide have been looking for a way to control this global threat. One of the most successful and practical solutions has been the development and worldwide distribution of the COVID-19 vaccines. However, in a small percentage of cases, vaccination can lead to de novo development or exacerbation of immune or inflammatory conditions such as psoriasis. Due to the immunomodulatory nature of this disease, people affected by psoriasis and other related skin conditions have been encouraged to receive COVID-19 vaccines, which are immunomodulatory by nature. As such, dermatological reactions are possible in these patients, and cases of onset, exacerbation or change in the type of psoriasis have been observed in patients administered with COVID-19 vaccines. Considering the rarity and minor nature of some of these cutaneous reactions to COVID-19 vaccination, there is a general consensus that the benefits of vaccination outweigh the potential risks of experiencing such side effects. Nevertheless, healthcare workers who administer vaccines should be made aware of the potential risks and advise recipients accordingly. Furthermore, we suggest careful monitoring for potentially deleterious autoimmune and hyperinflammatory responses using point-of-care biomarker monitoring.

Statins: Beneficial Effects in Treatment of COVID-19.

The recent viral disease COVID-19 has attracted much attention. The disease is caused by SARS-CoV-19 virus which has different variants and mutations. The mortality rate of SARS-CoV-19 is high and efforts to establish proper therapeutic solutions are still ongoing. Inflammation plays a substantial part in the pathogenesis of this disease causing mainly lung tissue destruction and eventually death. Therefore, anti-inflammatory drugs or treatments that can inhibit inflammation are important options. Various inflammatory pathways such as nuclear factor Kappa B (NF-κB), signal transducer of activators of transcription (STAT), nod-like receptor family protein 3 (NLRP), toll-like receptors (TLRs), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways and mediators, such as interleukin (IL)-6, IL-1ß, tumor necrosis factor-α (TNF-α), and interferon-γ (INF-γ), cause cell apoptosis, reduce respiratory capacity and oxygen supply, eventually inducing respiratory system failure and death. Statins are well known for controlling hypercholesterolemia and may serve to treat COVID-19 due to their pleiotropic effects among which are anti-inflammatory in nature. In this chapter, the anti-inflammatory effects of statins and their possible beneficial effects in COVID-19 treatment are discussed. Data were collected from experimental and clinical studies in English (1998-October 2022) from Google Scholar, PubMed, Scopus, and the Cochrane Library.