Clinicopathological Study of 307 Patients with Lichen Planus Actinicus and Pigmentosus Referred to Razi Skin Hospital From 2016 to 2021.

INTRODUCTION: The two less-known subtypes of lichen planus (LP) are lichen planus actinicus (LPA) and lichen planus pigmentosus (LPP), with the highest prevalence in the Middle East. OBJECTIVES: We aimed to evaluate the clinicopathological profile of these patients. METHODS: Three hundred and seven cases including 184 LPA and 123 LPP patients were recruited from the registered pathology reports of Razi Skin Hospital of Tehran from April 2016 to March 2021. The clinical features and pathological reports were extracted and analyzed. RESULTS: Among 307 patients, 117 (63.9%) in the LPA group and 88 (71.5%) in the LPP group were women. Duration of disease ranged from 1 month to 20 years and 1 month to 12 years in the LPA and LPP groups, respectively. Face (159 patients), limbs (68), and neck (23) were the most frequent sites of involvement in LPA patients, whereas face (60 patients), limbs (47), and trunk (42) were more commonly involved in the LPP patients. Pruritus and oral mucosal lesions were found with similar frequency in both groups. Pathological evaluation showed vacuolar degeneration of basal layer (100%), lymphocytes infiltration (97.3%), and melanin incontinence (58.2%) as the most frequent findings in LPA and vacuolar degeneration of basal layer (100%), lymphocytes infiltration (100%), and melanin incontinence (52/8%) as the most frequent findings in LPP cases. CONCLUSIONS: LPA and LPP were both more prevalent among women. Face was the most common site of involvement in both LPA and LPP. Vacuolar degeneration, lymphocyte infiltration, melanin incontinence, and hyperkeratosis were more common histological findings in this study.

Do we miss rare adverse events induced by COVID-19 vaccination?

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused many complications, the invention of coronavirus disease 2019 (COVID-19) vaccines has also brought about several adverse events, from common side effects to unexpected and rare ones. Common vaccine-related adverse reactions manifest locally or systematically following any vaccine, including COVID-19 vaccines. Specific side effects, known as adverse events of particular interest (AESI), are unusual and need more evaluation. Here, we discuss some of the most critical rare adverse events of COVID-19 vaccines.

Galangin Nanoparticles Protect Acetaminophen-Induced Liver Injury: A Biochemical and Histopathological Approach.

One of the main causes of acute liver failure is overdose with acetaminophen. Excessive consumption of acetaminophen leads to the production of NAPQI (N-acetyl-p-benzoquinone imine) through the activity of the enzyme cytochrome c oxidase. For this purpose, the effect of galangin nanoparticles with antioxidant activities will be evaluated for the treatment of acetaminophen-induced hepatotoxicity. In this study, after the synthesis of galangin nanoparticles and particle size determination, mice were divided into six groups. Before treatment, a single dose (350 mg/kg) of acetaminophen was administered by gavage in all groups. The activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), as well as biochemical factors FRAP and MDA in serum were measured and a histopathological study was performed. The prepared nanoparticles produced in this research were characterized by the SEM, DLS, and ZETA potential, and the average particle size was obtained in the range of 150 nm. Serum levels of liver enzymes (AST and ALT) in the nanoparticle group decreased significantly compared with the control group (P < 0.05). In the group without treatment, the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes increased significantly compared with the treatment groups. Also, galangin nanoparticles, at a dose of 20 mg/kg, improve cell damage in hepatocytes and preserve the tissue structure of the liver. Galangin nanoparticles reduce the acetaminophen-induced hepatotoxicity by reducing the number of liver function indices. According to our findings, the liver-protective effects of the nanoparticle may be due to its antioxidant properties.

COVID-19 in Iran: clinical presentations and outcomes in three different surges of COVID-19 infection.

BACKGROUND: A few studies compared the characteristics and outcomes of COVID-19 patients during the first and second surges of the disease. We aimed to describe the clinical features and outcomes of COVID-19 patients across the first, second, and third surges of the disease in Tehran, Iran. METHOD: We conducted a retrospective cohort study of patients with COVID-19 admitted to Sina hospital in Tehran, Iran, during three surges of COVID-19 from February 16 to October 28, 2020. RESULT: Surge 1 patients were younger with more prevalence of hypertension. They also presented with significantly higher oxygen saturation, systolic blood pressure, and respiratory rate on admission. Patients had higher levels of neutrophil to lymphocyte ratio, Urea, CRP, and ESR, in surge 2. The incidence of dyspnea, chest pain, and neurological manifestations followed a significant increasing trend from surge 1 to surge 3. There was no difference in severity and in-hospital mortality between the surges. However, the length of hospital stays and acute cardiac injury (ACI) was less in surge 1 and acute respiratory distress syndrome (ARDS) in surge 2 than in other surges. CONCLUSION: Patients did not significantly differ in disease severity, ICU admission, and mortality between surges; however, length of hospital stay and ACI increased during surges, and the number of patients developing ARDS was significantly less in surge 2 compared to other peaks.

The Yin and Yang of toll-like receptors in endothelial dysfunction.

Endothelial cells (ECs) play a critical role in health and disease due to their widespread distribution and unique location. Although ECs are not regarded as classical immune cells, they actively participate in innate immune and inflammatory responses. EC function is affected by exogenous activators (i.e., infectious agents) and endogenous triggers (i.e., damage-associated molecular pattern molecules (DAMPs) released by stressed or injured cells). Toll-like receptors (TLRs) can recognize both infectious agents and DAMPs and play a key role in activating innate mechanisms in ECs. Endothelial dysfunction (EDF) may lead to tissue damage in various inflammatory and autoimmune diseases through TLRs. This review summarizes the current knowledge about the role of TLRs in a variety of EDF-related conditions, including autoimmunity and graft rejection, cancer, cardiovascular diseases, diabetes and related complications, ischemia and related injuries, and sepsis.

Protective Effect of Kaempferol and Its Nanoparticles on 5-Fluorouracil-Induced Cardiotoxicity in Rats.

BACKGROUND: Fluorouracil (5-FU) is the third most common chemotherapeutic agent used in the treatment of solid tumors. 5-FU-associated cardiotoxicity ranks the second causes of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Kaempferol (KPF), a common flavonoid, possessing anti-inflammatory, antiapoptotic, antioxidative properties, and its protective effects on cardiovascular disease has been reported in various studies. The current study is aimed at appraising the effect of KPF and KPF nanoparticles (NPs) on 5-FU-induced cardiotoxicity in rats. METHODS: Thirty Male Wistar rats were divided into five groups as follows: control, 5-FU, 5-FU+10 mg/kg vitamin C, 5-FU+ 1 mg/kg KPF, and 5-FU+ 1 mg/kg KPF-NPs. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-FU (100 mg/kg). The control group received normal saline, and the treatment groups received KPF and KPF-NPs with an intraperitoneal injection for 14 days. Each heart histopathological lesions were given a score of 0 to 3 in compliance with the articles for statistical analysis. RESULTS: 5-FU resulted in a significant cardiotoxicity represented by an increase in cardiac enzymes, MDA (malondialdehyde) levels, COX-2 (cyclooxygenase-2) expression, and histopathological degenerations. 5-FU treatment also decreased body weight, TAC (total antioxidant capacity) values, VEGF (vascular endothelial growth factor) expression, blood cells, and hemoglobin (Hb) levels. Treatment with KPF and KPF-NPs reduced oxidative stress, cardiac enzymes, COX-2 expression, and VEGF expression. The number of blood cells, Hb levels, and histopathological degenerations, in cardiac tissue also body weight of animals, increased, followed by treatment with KPF and KPF-NPs. CONCLUSION: Our results demonstrated that treatment with KPF and KPF-NPs significantly improved cardiotoxicity induced by 5-FU in rats.

Colchicine Ameliorates 5-Fluorouracil-Induced Cardiotoxicity in Rats.

Background and Objective. 5-Fluorouracil is one of the most common chemotherapeutic agents used in the treatment of solid tumors. 5-Fluorouracil-associated cardiotoxicity is the second cause of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Colchicine is a strong anti-inflammatory drug used to prevent and treat acute gout and treat familial Mediterranean fever. And also, its protective effects on cardiovascular disease have been reported in various studies. The current study is aimed at appraising the effect of colchicine on 5-fluorouracil-induced cardiotoxicity in rats. Methods. Twenty male Wistar rats were divided into four groups as follows: control, 5-fluorouracil, colchicine (5 mg/kg), and 5-fluorouracil+5 mg/kg colchicine. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-fluorouracil (100 mg/kg). The control group received normal saline, and the treatment groups received colchicine with an intraperitoneal injection for 14 days. Findings. 5-Fluorouracil resulted in significant cardiotoxicity represented by an increase in cardiac enzymes, malondialdehyde levels, cyclooxygenase-2 and tumor necrosis factor-alpha expression, cardiac enzymes, and histopathological degenerations. 5-Fluorouracil treatment also decreased body weight, total antioxidant capacity and catalase values, blood cells, and hemoglobin levels. In addition, 5-fluorouracil disrupted electrocardiographic parameters, including increased elevation in the ST segment and increased QRS duration. Treatment with colchicine reduced oxidative stress, cardiac enzymes, histopathological degenerations, and cyclooxygenase-2 expression in cardiac tissue, improved electrocardiographic disorders, and enhanced the number of blood cells and total antioxidant capacity levels. Moreover, body weight loss was hampered after treatment with colchicine. Our results demonstrated that treatment with colchicine significantly improved cardiotoxicity induced by 5-fluorouracil in rats.

Aluminum Poisoning with Emphasis on Its Mechanism and Treatment of Intoxication.

Aluminum poisoning has been reported in some parts of the world. It is one of the global health problems that affect many organs. Aluminum is widely used daily by humans and industries. Residues of aluminum compounds can be found in drinking water, food, air, medicine, deodorants, cosmetics, packaging, many appliances and equipment, buildings, transportation industries, and aerospace engineering. Exposure to high levels of aluminum compounds leads to aluminum poisoning. Aluminum poisoning has complex and multidimensional effects, such as disruption or inhibition of enzymes activities, changing protein synthesis, nucleic acid function, and cell membrane permeability, preventing DNA repair, altering the stability of DNA organization, inhibition of the protein phosphatase 2A (PP2A) activity, increasing reactive oxygen species (ROS) production, inducing oxidative stress, decreasing activity of antioxidant enzymes, altering cellular iron homeostasis, and changing NF-kB, p53, and JNK pathway leading to apoptosis. Aluminum poisoning can affect blood content, musculoskeletal system, kidney, liver, and respiratory and nervous system, and the extent of poisoning can be diagnosed by assaying aluminum compounds in blood, urine, hair, nails, and sweat. Chelator agents such as deferoxamine (DFO) are used in the case of aluminum poisoning. Besides, combination therapies are recommended.

The interplay between aryl hydrocarbon receptor, H. pylori, tryptophan, and arginine in the pathogenesis of gastric cancer.

Several risk factors are known to be involved in the initiation and development of gastric cancer. Among them, H. pylori is one of the most prominent with multiple virulence factors contributing to its pathogenicity. In this study, we have discussed an interesting immunological cycle exploring the interplay between H. pylori, aryl hydrocarbon receptor (AHR), tryptophan, arginine, and the metabolites of these two amino acids in the development of gastric cancer. AHR is a ligand-activated transcription factor which acts as a regulator for a diverse set of genes and has various types of exogenous and endogenous ligands. The tryptophan metabolite, kynurenine, is one of these ligands that can interact with AHR, leading to immune suppression and subsequently, susceptibility to gastric cancer. On the other hand, H. pylori downregulates the expression of AHR and AHR repressor (AHRR), leading to increased inflammatory cytokine production. A metabolite of the kynurenine pathway, xanthurenic acid, is a potent inhibitor of a terminal enzyme in the synthetic pathway of tetrahydrobiopterin (BH4). BH4, itself, is a cofactor in the process of nitric oxide (NO) production from arginine that has been shown to have immune-enhancing properties. Arginine has also been evidenced to have anti-tumoral function through inducing apoptosis in gastric cell lines; however, controversy exists regarding the anti-tumor role of arginine and BH4, since they are also associated with increased NO production, subsequently promoting tumor angiogenesis. Hence, although several synergistic connections result in immunity improvement, these correlations can also act as a double-edged sword, promoting tumor development. This emphasizes on the need for further investigations to better understand this complex interplay.

Antibody Fragment and Targeted Colorectal Cancer Therapy: A Global Systematic Review.

BACKGROUND AND AIMS: Antibody-based therapeutics have been shown to be promising for the treatment of colorectal cancer patients. However, the size and long-circulating half-lives of antibodies can limit their reproducible manufacture in clinical studies. Consequently, in novel therapeutic approaches, conventional antibodies are minimized and engineered to produce fragments like Fab, scFv, nanobody, bifunctional antibody, bispecific antibody, minibody, and diabody to preserve their high affinity and specificity to target pharmaceutical nanoparticle conjugates. This systematic review for the first time aimed to elucidate the role of various antibody fragments in colorectal cancer treatment. METHODS: A systematic literature search in the web of sciences, PubMed, Scopus, Google Scholar, and ProQuest was conducted. Reference lists of the articles were reviewed to identify the relevant papers. The full-text search included articles published in English during 19902021. RESULTS: Most of the 53 included studies were conducted in vitro and in most conducted studies singlechain antibodies were among the most used antibody fragments. Most antibodies targeted CEA in the treatment of colorectal cancer. Moreover, a large number of studies observed apoptosis induction and tumor growth inhibition. In addition, few studies implicated the role of the innate immune system as an indirect mechanism of tumor growth by enhancing NK-cell killing. CONCLUSION: Antibody-based therapy was demonstrated to be of great promise in the treatment of colorectal cancer rather than common treatments such as radiotherapy, chemotherapy, and surgical operations. This type of specified cancer treatment can also induce the activation of the innate and specific immune systems to eradicate tumor cells.

Stem Cell-based Therapeutic and Diagnostic Approaches in Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative impairment mainly recognized by memory loss and cognitive deficits. However, the current therapies against AD are mostly limited to palliative medications, prompting researchers to investigate more efficient therapeutic approaches for AD, such as stem cell therapy. Recent evidence has proposed that extensive neuronal and synaptic loss and altered adult neurogenesis, which is perceived pivotal in terms of plasticity and network maintenance, occurs early in the course of AD, which exacerbates neuronal vulnerability to AD. Thus, regeneration and replenishing the depleted neuronal networks by strengthening the endogenous repair mechanisms or exogenous stem cells and their cargoes is a rational therapeutic approach. Currently, several stem cell-based therapies as well as stem cell products like exosomes, have shown promising results in the early diagnosis of AD. OBJECTIVE: This review begins with a comparison between AD and normal aging pathophysiology and a discussion on open questions in the field. Next, summarizing the current stem cell-based therapeutic and diagnostic approaches, we declare the advantages and disadvantages of each method. Also, we comprehensively evaluate the human clinical trials of stem cell therapies for AD. METHODOLOGY: Peer-reviewed reports were extracted through Embase, PubMed, and Google Scholar until 2021. RESULTS: With several ongoing clinical trials, stem cells and their derivatives (e.g., exosomes) are an emerging and encouraging field in diagnosing and treating neurodegenerative diseases. Although stem cell therapies have been successful in animal models, numerous clinical trials in AD patients have yielded unpromising results, which we will further discuss.

Protective Effect of Quercetin Nanoemulsion on 5-Fluorouracil-Induced Oral Mucositis in Mice.

The target of this study was to evaluate the efficacy, histopathological, oxidative stress, and molecular effects of quercetin (QRC) in mice with oral mucositis induced by 5-fluorouracil (5-FU). Thirty-six albino male mice with oral mucositis induced by 5-FU as a chemotherapeutic agent were used in this study. The animals were randomly divided into 6 groups: control group, mucositis (MUC) group, pretreatment group, posttreatment group, and two last groups including nanoemulsion form of QRC with a dose of 5 mg/kg in both pretreatment and posttreatment. In the present evaluation, fewer oral lesions were observed in the QRC posttreatment groups compared to the pretreatment and nanoemulsion receiving groups. In the SOD assay, the most significant difference was observed in the posttreatment nanogroup (41.073 ± 1.24) and pretreatment nanogroup (43.453 ± 2.60) in comparison to the 5-FU group (30.897 ± 1.93). The results of CAT assay also showed a significant difference in nano-posttreatment (124.60 ± 10.85), posttreatment (135.4 ± 9.82), and nano-pretreatment groups (128.80 ± 7.20) compared to the 5-FU group (55.07 ± 8.91). The expression of inflammatory genes such as Hif-1α and NfκB in this group was lower than in the other groups, although this difference was not significant. It seems that the use of QRC can improve the treatment process of oral mucositis induced by 5-FU.

Ameliorative effect of Alpinia officinarum Hance extract on nonylphenol-induced reproductive toxicity in male rats.

Nonylphenol (NP), an endocrine-disrupting chemical, interferes with reproductive function and induces oxidative stress in different organs, including the testis and prostate. Alpinia officinarum Hance (ALP), a plant species of the Zingiberaceae family, has proven antioxidant properties. This study aimed to evaluate the effect of the alcoholic extract of ALP treatment on NP-induced reproductive toxicity and oxidative stress in male rats using biochemical and histopathological biomarkers. Our experimental groups were defined as follows: oil treatment (control), NP 10 mg/kg, ALP 10 mg/kg (ALP HD), NP + ALP 5 mg/kg (NP + ALP LD) and NP + ALP 10 mg/kg (NP + ALP HD). NP administration caused significant cytotoxicity and a significant increase in oxidative stress prostate-specific antigen (PSA) levels accompanied by a significant reduction in testosterone levels. The relative weight of the testis of both NP + ALP LD and NP + ALP HD groups was significantly decreased compared to the control group. Histopathological evaluations revealed destructive effects in testis and prostate tissue samples. In conclusion, ALP administration improved cytotoxicity, oxidative stress, testosterone and PSA levels, and testis and prostate tissue destructive effects induced by the NP in male rats.

An epidemiological study of poisoning cases in Babol (northern Iran) from 2015 to 2018.

BACKGROUND: Poisoning is a major public health problem that constitutes a significant share of the global burden of disease. Previous studies conducted in this area indicated the importance of such epidemiological studies. The most critical impact of these studies is their effect on changing current regulations and, therefore, decreasing poisoning cases. We aimed to evaluate all poisoning cases with regard to the patients' demographics and the involved intoxicants. METHODS: The present study was conducted to investigate all poisoning cases who were admitted during a three-year period. Causes of poisoning, hospitalization, management procedures and outcome of the cases were surveyed. A total of 1448 patients referred to Shahid Beheshti Hospital (Babol, Iran) from 2015 to 2018. RESULTS: More than half of the patients were females (51.7%), and the majority of poisoning cases were seen in patients aged between 15 to 25 years (34.2%). It was found that suicide made a large part of poisoning cases (65.6%), and females tend to attempt suicide more than males (64.3% vs. 35.7%, respectively). Also, regular drugs followed by club drugs were the most abundant toxic agents (52.1% and 23.3%, respectively). Aluminum phosphide (AlP) was the most lethal intoxicant in our study, accounting for 68.2% of all deaths. CONCLUSION: According to the results, it is concluded that the existing regulations for drug control and suicide prevention have not been efficient enough and further actions yet to be made to reduce the consequences of drug- and non-drug-related toxicities.

SARS-CoV-2 infection in patients with diabetes mellitus and hypertension: a systematic review.

After the emergence of the novel 2019 coronavirus disease in P. R. China, this highly contagious disease has been currently spread out to almost all countries, worldwide. Novel 2019 coronavirus disease, Middle East respiratory syndrome, and severe acute respiratory syndrome are reported to cause a higher risk for severe infections in patients with chronic comorbidities, such as hypertension and diabetes. These severe infections can contribute to higher rates of morbidity and mortality in these patients. In the present review, we discussed the role and underlying mechanisms of the two most common chronic diseases, type-2 diabetes mellitus and hypertension, in clinical manifestations and disease severity of novel 2019 coronavirus disease, Middle East respiratory syndrome and severe acute respiratory syndrome, with the hope to provide evidence for better decision-making in the treatment of this vulnerable population.

Angiotensin-converting enzyme 2 (ACE2) receptor and SARS-CoV-2: Potential therapeutic targeting.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta coronavirus that uses the human angiotensin-converting enzyme 2 (ACE2) receptor as a point of entry. The present review discusses the origin and structure of the virus and its mechanism of cell entry followed by the therapeutic potentials of strategies directed towards SARS-CoV2-ACE2 binding, the renin-angiotensin system, and the kinin-kallikrein system. SARS-CoV2-ACE2 binding-directed approaches mainly consist of targeting receptor binding domain, ACE2 blockers, soluble ACE2, and host protease inhibitors. In conclusion, blocking or manipulating the SARS-CoV2-ACE2 binding interface perhaps offers the best tactic against the virus that should be treated as a fundamental subject of future research.

Contribution of inflammasome complex in inflammatory-related eye disorders and its implications for anti-inflammasome therapy.

Inflammasome complex is regarded as a major molecular regulator that exerts a significant function in caspase-1 activation and consequently, the development of cytokines like interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). The secretion of these cytokines may induce inflammation. The role of inflammasomes in the pathologic process of eye-related illnesses like glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy has been well studied over the past decade. However, the detailed pathogenic mechanism of inflammasomes in these retinal diseases is still unknown. Therefore, further investigation and understanding various aspects of inflammasome complexes as well as their pivotal roles in the immunopathology of human ocular illnesses are essential. The present review aims to describe the significant involvement of inflammasomes in the immunopathology of important inflammatory retinal illnesses, including glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy focusing on anti-inflammasome therapy as a promising approach in the treatment of inflammation-related eye diseases.

Curcumin-loaded nanoparticles: a novel therapeutic strategy in treatment of central nervous system disorders.

Curcumin as a hydrophobic polyphenol is extracted from the rhizome of Curcuma longa. Curcumin is widely used as a dietary spice and a topical medication for the treatment of inflammatory disorders in Asia. This compound also possesses remarkable anti-inflammatory and neuroprotective effects with the ability to pass from the blood brain barrier. Based on several pharmacological activities of curcumin, it has been introduced as an ideal candidate for different neurological disorders. Despite the pleiotropic activities of curcumin, poor solubility, rapid clearance and low stability have limited its clinical application. In recent years, nano-based drug delivery system has effectively improved the aqueous solubility and bioavailability of curcumin. In this review article, the effects of curcumin nanoparticles and their possible mechanism/s of action has been elucidated in various central nervous system (CNS)-related diseases including Parkinson's disease, Huntington disease, Alzheimer's disease, Multiple sclerosis, epilepsy and Amyotrophic Lateral Sclerosis. Furthermore, recent evidences about administration of nano-curcumin in the clinical trial phase have been described in the present review article.