Cardiovascular diseases are the leading cause of death worldwide. There are many evidences that the dysfunctioning lipotoxicity is the one of major factors of cardiovascular diseases such as, atherosclerosis, hypertension, and coronary heart disease. Obesity and diabetes increase circulating lipids that are likely with more generation of toxic intermediates, which leading to the complications associated with cardiovascular diseases. Indeed, lipotoxicity is a metabolic syndrome caused by abnormal lipid accumulation, which leads to cellular dysfunction and necrosis. Here we review the factors that induced pathogenesis of cardiovascular diseases by lipid accumulation and the mechanisms underlying the lipotoxicity.

Objective: In end stage renal disease, the synthesis of vitamin D is disturbed.Hyperparathyroidism is one of the key factors in the pathogenesis of many of the complications of dialysis mainly bone and cardiovascular complications.Aim:This study aimed at assessing vitamin D receptor gene polymorphisms BsmIand FokI in Egyptian patients with end stage renal disease on maintenance haemodialysis and the assosciation of these polymorphisms with cardiovascular complications and hyperparathyroidism among these patients. Methods: One hundred subjects, recruited from Medical Research Institute, from March to July 2014, divided into two main groups; the control group which included thirty apparently healthy subjects and the patients group which included seventy patients with end stage renal disease on maintenance haemodialysis with median 4 years. To all studied subjects, detailed history was taken, thorough physical examination, carotid intima media thickness, presence of plaques and ECG ischemic changes. Laboratory investigations included serum levels of: glucouse, urea, creatinine, uric acid, albumin, total cholesterol, low and high density lipoproteins, calcium, phosphorus, and CRP as well as plasma PTH level. For molecular studies, the detection of BsmI and FokI polymorphisms using polymerase chain reaction and restriction fragment length polymorphism (PCR / RFLP) technique. Results: 1.No statistically significant difference could be detected in both BsmI and FokI gene polymorphisms between the hemodialysis patients and the controls, suggesting that the development of ESRD had no relation with either VDR BsmI or FokI gene polymorphisms.2.No statistically significant difference were found in these polymorphisms between the hemodialysis patients with or without cardiovascular complications or between patients with PTH level less or more than 300 pg/ml. These results suggest that the development of cardiovascular complications and secondary hyperparathyroidism among Egyptian patients on maintenance haemodialysis cannot be attributed to these two gene polymorphisms. Conclusion: No association could be found between the variant alleles of BsmI and FokI gene polymorphisms and the development of ESRD, cardiovascular complications and secondary hyperparathyroidism among the studied samples of Egyptian patients on maintenance haemodialysis.

Uterine sections from 6 patients with incidental nodal lymphangioleiomyomatosis (LAM) were examined for LAM lesions by screening these sections with cathepsin K immunohistochemistry (IHC) stains. The hysterectomy specimens were all concurrent with the lymph node dissections in which the nodal LAM was discovered. In 4 of 6 patients microscopic lesions of pre-LAM were identified and confirmed by IHC staining for HMB-45 and beta-catenin. All lesions were grossly inapparent and also inapparent by routine hematoxylin and eosin stains. Three variants of pre-LAM lesions were identified. None of the pre-LAM lesions had an associated lymphatic proliferation. It is proposed that these pre-LAM lesions gave rise to the incidental nodal LAM lesions. Furthermore, it is suggested that the absence of an associated lymphatic proliferation associated with these lesions may be a factor in the attenuated potential for spread and the only rare association of these nodal lesions with pulmonary LAM.

Emerging evidence indicates that micronutrient deficiency could play a significant role in the pathogenesis and progression of many chronic diseases including diabetes mellitus, hypertension, obesity, dyslipidemia, hyperuricemia, kidney disease, cancer, anemia and other cardio-metabolic and neurodegenerative diseases through the induction of Insulin resistance (IR). However, there are still gaps in our scientific knowledge regarding the links between micronutrient deficiencies, IR, and cardio metabolic disorders. This review provides current information on recent advances and a global perspective regarding the relationship between micronutrient deficiency, IR, and cardio metabolic disorders. Empirical evidence indicates that deficiencies in either micronutrients associated with insulin activity (such as Chromium, manganese, magnesium, and iron) or antioxidant enzyme cofactors (such as vitamin A, copper, zinc, and manganese) could impact several physiological processes leading to a cascade of metabolic and biochemical derangements such as B-cell apoptosis, loss of islet cell mass, defective tyrosine kinase activity, oxidative stress, pancreatic β-cell dysfunction, reduction in lean body mass, defective insulin signaling mechanism, elevated protein kinase C activity, and excess intracellular calcium. Collaboratively, these states of metabolic malfunctioning are associated with IR, which triggers the onset of many cardio metabolic diseases. Undoubtedly, the prevention of micronutrient deficiency may indeed ameliorate the incidence of IR and cardio-metabolic disorders in those at risk and in the general population.

The pandemic of COVID-19 has adversely affected the world in many aspects. The health and economic sectors suffer most of the repercussions of this disease. The search for a cure for this rapidly spreading virus which is causing massive life losses worldwide requires clear understanding of the immunopathogenesis of this virus so as to develop pinpointed targeted therapies rather than relying mainly on supportive care measures and drug repurposing to fight this life-threatening virus infection. Neutrophils, neutrophil extracellular traps (NETs), and NETosis are not well studied not only in COVID-19, but also in coroviruses in general. The review will shed lights on the functions of neutrophils, NETs, and NETosis in various infectious complications as well as in sepsis and acute lung conditions in an attempt to understand their actual roles and in order to help in designing targeted therapies in the near future.

Varicella zoster virus behaves differently from other herpes viruses as it differs from them in many aspects. Recently, there has been growing evidence on the beneficial effects of the virus in immune compromised hosts and these effects are translated into prolongation of survival. The reported beneficial effects of the virus include: (1) stimulation of bone marrow activity in patients with hematologic malignancies and bone marrow failure syndromes, (2) antitumor effects in various hematologic malignancies and solid tumors, and (3) association with graft versus host disease which has anticancer effects. Additionally, there are several reports on the safety of the live-attenuated even in severely immune suppressed individuals and on the emerging role of the virus in cancer immunotherapy. In this review, the following aspects of the virus will be thoroughly discussed: (1) new data on the genetic background, pathogenesis, vaccination, and new therapeutic modalities; (2) bone marrow microenvironment and hematopoiesis; (3) cells involved in the pathogenesis of the virus such as: mesenchymal stem cells, dendritic cells, natural killer cells, T-cells and mononuclear cells; (4) cellular proteins such as open reading frames, glycoproteins, promyelocytic leukemia protein, chaperons, and SUMOs; (5) extracellular vesicles, exosomes, and micro-RNAs; and (6) signaling pathways, cytokines, and interferons.

There is growing evidence that gastroesophageal disease is influenced by the esophageal microbiome, and that commensal bacteria of the oropharynx, stomach, and colon are thought to have a role in modulatiing pathogenesis. These emerging hypotheses are based on observed changes in the composition of the esophageal flora, notably, repeated observations: 1. There is an abundance of gram-positive bBacteria in the healthy esophagus. are more gram positive prevalent 2. The esophageal bacterial population becomes increasingly gram negative with disease progression. Associated with this shift to a more gram negative prevalence is an increase in the potential for the presence of antigenic lipopolysaccharide (LPS). The immunoreactivity of LPS endotoxin thought to promote susceptibility to inflammation and disease. The pathogenesis of the more common diseases of the esophagus e.g. gastroesophageal reflux disease (GERD), esophageal dysmotility (achalasia), eosinophilic esophagitis (EoE), Barrett’s esophagus (BE), and esophageal cancer, are well-established. Emerging data suggest however, that these are all characterized by an immune-mediated inflammatory cascade, propogated by a dysbiotic state. Thereby, the ability of the healthy “normative state” to protect against foreign bacteria is compromised. This dysbiosis thereby can create adverse inflammatory or immunoregulatory responses with progression of disease. In the normal healthy state, the esophageal microbiome is constituted in-part, by a multitude of gram positive bacteria, many of which produce antibacterial peptides called bacteriocins. Bacteriocins are selective and used to maintain population integrity by killing off foreign bacteria. When the “normative biome” is interrupted (e.g. antibiotics, medications, diet, environmental factors), the constitutional changes may allow a more hospitable imbalance favoring the proliferation of opportunistic pathogens. Therefore it seems rational that defining, perhaps that defining, perhaps cultivating, a protective bacterial community that could help prevent or mitigate inflammatory diseases of the esophagus. Furthermore, in conjunction with evidence demonstrating that some bacteriocins are cytotoxic or antiproliferative toward cancer cell lines, further exploration might provide a rich source of effective peptide-based drug targets. Therapeutic options targeting the microbiome, including prebiotics, probiotics, antibiotics and bacteriocins, have been studied, albeit the attributable effects on the esophagus for the most part, have been unrecognized by clinicians. This review focuses on the current knowledge of the involvement of the microbiome in esophageal diseases (most notably GERD/Barrett’s esophagus/esophageal cancer) and identifies emerging new concepts for treatment.

Background: Multiple sclerosis (MS) is an autoimmune disorder of the central nerve system (CNS), which affects the brain and spinal cord. Experimental autoimmune encephalomyelitis (EAE) is the most commonly applied experimental model for studying the MS. The aim of this study was to determine the effects of Sesamum indicum seeds oil on Experimental Autoimmune Encephalomyelitis (EAE) in mice. Methods: Sesame oil was administrated intraperitoneally three days before immunization. IFN-γ, IL-10, IL-17 and TGF-β levels and mRNA expression in supernatant of and within cultured mononuclear cells were assessed. Results: According to our results, sesame oil treated mice demonstrated significant disease severity reduction (P=0.01 and 0.001, respectively). Treated EAE mice also represented statistically significant delay in the onset of symptoms in comparison with control group. The average IFN-γ levels and mRNA of sesame oil treated EAE mice were less than untreated EAE group. IL-10 and TGF-β levels and mRNA did not differ significantly in sesame oil treated EAE mice in comparison to untreated EAE group. IL-17 levels and mRNA were also found to be decreased significantly in treated mice in comparison to untreated mice. Conclusions: Even thoughTH1 and TH17 cells through secretion of IFN-γ and IL-17, respectively, are involved in the pathogenesis of multiple sclerosis and EAE, but IL-10 has been shown to exhibit suppressive effects on these disorders. It can be concluded that sesame oil is able to induce TH2 and TH17-related immune responses and suppress TH1 type in EAE

Asthma is a chronic respiratory disease which characterized by recurrent airflow obstruction, wheezing, chest tightness and coughing. Management of allergic asthma especially in children, is main problem for industrial world. Immunological factors have critical role in pathogenesis of allergic asthma. Cytokines as major controller of immune system, are important in this reaction. Allergic asthma is a disease with symptoms: eosinophilic inflammation, mucus hyper secretion, airway obstruction, airways hyperresponsivness, IgE high level production, smooth muscle spasm. Cytokines have main and complicated role in pathophysiology of allergic asthma.

Gastroesophageal reflux disease (GERD) is a quite common disease caused by the reflux of gastric contents into the esophagus and manifested by heartburn and acid regurgitation. Apart from the esophageal manifestations, GERD is implicated in extraesophageal manifestations including pulmonary manifestations i.e. asthma, chronic cough, pneumonia, idiopathic pulmonary fibrosis, otolaryngological manifestations i.e. laryngitis, otitis, polyps, cancer of the larynx, chest pain [1,2]. The relationship between GERD and pulmonary manifestations is quite challenging and ongoing research efforts have focused on the elucidation of the pathogenesis of GERD induced asthma. 

Asthma is a chronic inflammatory disease of the airways characterized by airway inflammation, bronchial hyperresponsiveness, reversible airflow obstruction and recurrent symptoms. Patients often present with coughing, wheezing, dyspnea, and chest tightness, were they usually responds to the mainstay of treatment that relies on inhaled glucocorticoids (ICS), and long acting β2 agonist (LABA), along with leukotriene. In around 20% of the patient’s morbidity, mortality and cost of therapy increased because they fail to benefit from the existing gold standard therapy regimen. Both immunoglobulin-E (IgE), interlukin-5 (IL-5) had proven to play important major role in asthma pathogenesis. Over the past two decades biologic therapy that targeting IgE begins the era in treating severe asthma, and recently anti-IL-5, revealed major role in eosinophils maturation, activation, survival, and recruitment process of severe asthma. The different biologic therapy that is currently available in the market are supported by solid evidence from controlled randomized clinical trials, to guide the clinician on the type of patients that will benefit from the therapy, with an insight on the appropriate monitoring parameters and patient evaluation plans. This review was conducted by searching PubMed, EMBASE, and Google Scholar to identify peer-reviewed clinical trials, guidelines, and review articles published in English in the role of biologic therapy in severe asthma. The main aim from publishing this review is to summarize the current available evidence on the approved biologic therapy in treating patients with severe asthma.

Background: Globally, Alzheimer’s disease (AD) affects millions of elderly individuals are affected with AD who suffer from decline in cognitive ability. However, immune system dysfunction has a role in AD pathogenesis. However, pharmacological therapeutic intervention for caring of ADis not available. Therefore there is a need to develop novel therapeutic modalities for AD individual care. Objective: The objective of the this trial was to detect immune system and quality of life (QOL) response following aerobic versus resisted exercise training among AD subjects. Methods: Fifty older with AD disease the range of age ranged was 61 to 73 years enrolled in the current study. However, smoking, liver, chest, renal, metabolic and cardiac dysfunction considered as exclusion criteria. Participants were randomly enrolled into group (A) who applied aerobic exercise intervention, while group (B) applied resisted exercise intervention for period of six months. Results: The SF-36 which measure QOL along with in the immunological parameters (CD3 count, CD4 count, CD8 count and CD4/CD8 ratio) showed significant improvement following aerobic and resisted exercise. However, comparing between both groups showed significant differences with greater significant improvement in all measured parameters following aerobic exercise training (p < 0.05). Conclusion: Aerobic exercise is the most appropriate exercise to improve immune system and quality of life among elderly Alzheimer’s.

Background: Pulmonary fibrosis is a clinical problem with an enigmatic etiology with no effective therapy. Current therapies for lung fibrosis are ineffective for progression of lung fibrosis and preventing respiratory failure. Objectives: The aim of this study is to explore the expression of Desmin, α-smooth muscle actin (α-SMA) and the telomerase subunit: human telomerase reverse transcriptase (h-TERT) in a spectrum of lung tissue samples consist of lung fibrosis, lung cancer, and healthy controls. Materials and Methods: The expression of Desmin, α-SMA and hTERT were studied in samples of 15 pulmonary fibrosis samples, 16 samples of lung cancer and 14 healthy controls investigated. We evaluated Desmin, α-SMA as well as the expression of components of telomerase (TERT), by methods: RNA Extraction and cDNA synthesis, Real-Time quantitative PCR, Immunohistochemistry, all prepared from lung tissue paraffin blocked. Results: α-SMA marker detected 1(8.3%) of healthy control and 11(91.7%) of lung fibrosis samples. The difference between groups was significant (p<0.001). Also the difference between healthy control 1(6.7%) and lung cancer 14 (93.3%) for α-SMA marker was a significant (P<0.001). It was a significant difference between healthy control and lung cancer for TERT expression (P=.005). TERT was not positive in any sample of neither healthy control nor lung fibrosis. For TERT, it was a significant difference between lung fibrosis and lung cancer by Fisher’s Exact Test (P=.004). Expression of TERT and α-SMA between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was not statistically significant (P=.700, P=0758), respectively. Conclusions: We recommend more investigation to regard α-SMA, Desmin in patients with lung fibrosis and follow them for possible cancer risk. Also, more study is needed to regard TERT as a marker in lung cancer. Assessment of these markers may have future implication to explain the same way of pathogenesis and carcinogenesis of fibrosis and cancer and for prevention or treatment

The article presents the results of x-ray anatomical studies of 56 whole lung preparations, which were carried out immediately after the autopsy of children who died from АP. In 47 cases it was carried out the contrast of the vessels and in 9 cases the bronchial tree. The results allowed to clarify some details of the pathogenesis of АP and were additional arguments in support of the new doctrine of the disease.

Hairy polyp and choristoma are rare benign developmental malformations. Hairy polyp mainly occurs in the nasopharynx whereas choristoma occurs in the dorsum of the tongue. Aetiology and pathogenesis of both hairy polyp and choristoma still remain unknown. Diagnosis is made by histological examination and complete excision is the treatment of choice. We report a case of hairy polyp and choristoma on the palate and the dorsum of the tongue respectively in a seventeen days old baby.

Obesity is a chronic and metabolic disease with a high increasing prevalence worldwide. It has multifactorial pathogenesis including genetic and behavioral factors [1-5]. Overweight and obesity have been defined and classified by the World Health Organization (WHO) and the National Institutes of Health (NIH) [2,3]. A person with a normal weight has Body Mass Index (BMI) of 18.5-24.9. A person with a BMI under 18.5 is called underweight. An adult having a BMI of 25-29.9 is overweight and pre-obese. Class 1 obesity is defined as a BMI between 30.00-34.99. Class 2 (Severe) Obesity is to have a BMI between 35.00-39.99. Morbid (Extreme, Class 3) obesity is to have a BMI over 40 [1-5]. Obesity is significantly associated with enhanced morbidity and mortality rates. It has also various economic, medical and psychological effects and causes health problems including many systemic diseases, economic costs and burdens, social and occupational stigmatization and discrimination and productivity loss [4-6]. Obesity carries the increased risk of development of many systemic and chronic diseases, including sleep apnea, depression, insulin resistance, Type 2 (adult-onset) diabetes, Gout and related arthritis, degenerative arthritis, hypertension, dyslipidemia, heart disease such as myocardial infarction, congestive heart failure, or coronary artery disease, polycystic ovary syndrome and reproductive disorders, Pickwickian syndrome (obesity, red face and hypoventilation), metabolic syndrome, non-alcoholic fatty liver disease, cholecystitis, cerebrovascular accident, colonic and renal cancer, rectal and prostatic cancer in males, and gallbladder, uterus and breast cancer in females [6-12]. In recent years, some publications reported that obesity has been strongly associated with some ocular diseases including age-related cataract and maculopathy, glaucoma, and diabetic retinopathy [13-16]. The recent reports demonstrated that the central corneal thickness and intraocular pressure were increased while as mean thickness of RNFL and retinal ganglion cell and choroidal thickness (CT) were decreased in the morbidly obese subjects [17-19]. However, another study has reported that CT increased in obese children [20]. On the other hand, a recent study reported that all values of the specific tests used to evaluate the ocular surface were within the normal range [21]. In some experimental studies, it has been demonstrated that obesity may cause retinal degeneration [22,23]. Additionally, in a past meeting presentation, it has been speculated that keratoconus is associated with severe obesity [24]. Teorically, idiopathic intracranial hypertension, and papilledema may also be associated with obesity [25]. Obesity may be also a cause of mechanical eyelid abnormalities such as entropion [26]. However, further investigations are needed to detect the significant relationship between these diseases and obesity. On the other hand, the ocular surgeries of obese patients are difficult compared to normal weight-subjects. The posterior capsule rupture and vitreous loss may easily develop during cataract surgery of these patients because obese patients have an elevated vitreous pressure and operating table cannot often be lowered or surgeon’s chair cannot be elevated sufficiently to provide the clear viewing of the operating area and tissues. So, some different surgical manipulations such as standing phacoemulsification technique and reverse Trendelenburg position have been developed. Additionally, the standing vitrectomy technique has been used for vitreoretinal interventions in morbidly obese patients [27,28]. In conclusion, all obese subjects should be subjected to a completed ophthalmological examination and to relevant clinics for the detection of possible comorbidities and diseases

Cystoid macular edema is a common cause for unexplained painless vision loss after cataract surgery. Even the pathogenesis of pseudophakic cystoid macular edema (PCME) still remains undefined, it can most frequently occur in eyes with high vasoactive profile, had complicated cataract surgery such as posterior capsule rupture and risk of inflammation. Increased inflammation, ultimately leading to the breakdown of the blood-retinal barrier and cystic accumulation of extracellular intraretinal fluid. The natural history of PCME is spontaneous resolution without any treatment in most of patient, but it may take weeks or months, in addition permanent visual morbidity may occur in some cases. Therefore there is lack of consensus regarding treatment approach for this common ocular condition. In this review treatment alternatives of PCME and its relation with underlying patho-physiologic mechanism are evaluated.

Retinopathy of prematurity (ROP) is a consequence of an arrest in normal retinal neural and vascular development, which determines the aberrant retinal regeneration [1,2]. ROP is a disease process mostly reported in preterm neonates ranging from mild, transient changes in the retina with regression to severe progressive vasoproliferation, scarring, detachment of retina and blindness and it is common blinding disease in children and a major cause of vision loss among preterm infants [3]. Today it is well known that oxygen therapy is not the single causative factor, but many other risk factors play a causative role in the pathogenesis of ROP [4,5]. The risk factors for ROP include oxygen administration, hypoxia, hypercapnia, blood transfusion exchange transfusion, apnea,sepsis and total parenteral nutrition. The incidence of ROP has been reported to be similar in multiple and singleton births [6-8]. Twin studies show that from 70% to 80% of the susceptibility to ROP is conditioned by genetic factors [9,10]. Hence this study is to find out the incidence of ROP in twins in a tertiary care centre in a developing country. It also attempts to identify the difference in risk factors among twins which predispose to ROP in Neonatal Intensive Care Unit.

Bronchiolitis obliterans (BO) is an infrequent clinical syndrome characterized by the chronic obstruction of small airways due to fibrosis [1]. Intravenous immunoglobulin (IVIG) could be used for treatment while underlying immune mechanisms in the pathogenesis of BO exist [2]. Here, we present two children with BO due to adenovirus infection whose complaints resolved after IVIG replacement.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and its prevalence and incidence is also related to smoking behavior [1]. COPD is still a chronic inflammatory and progressive disease caused by multifactorial agents including environmental pollutants [2]. Besides that, it is emerging that endogenous epigenetic factors induced by lifestyle and environment [3] could play a role in the etiopathogenesis of the disease [4]. In the last years, several authors suggested that low vitamin D levels seem to be related with the increase of COPD manifestations [5]. Moreover, a multicentre, double-blind, randomised controlled trial documented that vitamin D supplementation protects against moderate or severe exacerbation of the disease, but not by upper respiratory infections [6]. However, low levels of vitamin D can be extended to many other diseases, including multiple sclerosis, diabetes, colon rectal cancer, headache or drug use [7-11]. Moreover, it is also important to remember that Vitamin D deficiency is common in high latitude regions, such as northern Europe, New Zealand, northern USA, and Canada where weaker ultraviolet B rays is not able to produce enough vitamin D. Finally, methodological factors (using low sensitivity methods) could contribute to misleading evaluation of circulating vitamin D levels. In any case, here we shall remind that vitamin D has a fundamental role in immunity [12]. In particular, it has been reported that vitamin D is able to shift the pro-inflammatory T-helper cell 1 to anti-inflammatory T-helper cell 2 [13]. Therefore, benefits of vitamin D supplementation in chronic diseases which directly or indirectly affect immune system are obvious. Today, the burden of COPD in never smokers is higher than previously believed. Therefore, more research is needed to unravel the characteristics of non-smokers COPD [1]. Notably, vitamin D levels are reported to be significantly lower in smoker’ssubjects than in non-smokers ones [14]. Therefore, low plasma vitamin D levels in COPD seems to be more a causality than a correlation.