Diagnostic and Prognostic Risk Assessment of Heat Shock Protein HSPA1B rs2763979 Gene Variant in Asthma.

Given the significant role the heat shock protein Hsp70 plays in modulating cellular homeostasis in several chronic inflammatory disorders, the genetic variation of the inducible HSP70 (HSPA1B) gene may impact protein expression and disease phenotype. The HSPA1B rs2763979 variant has been associated with multiple inflammatory scenarios, but no previous studies have explored its association with asthma. In this sense, this cross-sectional study enrolled 90 children with asthma and 218 age-/sex-matched healthy volunteers for rs2763979 variant genotyping by TaqMan allelic discrimination analysis. The results were investigated under several genetic models and associated with disease susceptibility and clinicolaboratory data. Overall analysis, including the 308 participants, revealed a higher C allele frequency among patients relative to controls (43.0% vs. 33%, p = 0.006). Furthermore, patients with the C variant initially had a higher risk of asthma under heterozygous (OR = 2.75, 95%CI = 1.46-5.18, p = 0.003), homozygous (OR = 3.35, 95%CI = 1.19-9.39, p = 0.008), dominant (OR = 2.83, 95%CI = 1.52-5.25, p < 0.001), and overdominant (OR = 2.12, 95%CI = 1.20-3.74, p = 0.008) models. However, after employing a 1:1 nearest propensity matching analysis, the studied variant showed only borderline significance with asthma under the dominant model in 71 matched cohorts. Interestingly, patients who carry the rs2763979 CC genotype showed favorable spirometric parameters in terms of better (mean ± SD) forced vital capacity (86.3 ± 7.4 vs. 77.7 ± 6.1 and 75.7 ± 7.2 for CT and TT, respectively, p = 0.021), forced expiratory volume in one second before bronchodilation (60.7 ± 12.9 vs. 54.9 ± 7.6 and 56.1 ± 7.5 for CT and TT, respectively, p = 0.021), and an improvement in peak expiratory flow rate after inhaled salbutamol bronchodilator (p = 0.044) relative to the counterpart genotypes. In conclusion, the HSPA1B rs2763979 variant might have prognostic utility as a genetic marker for asthma in our population. Further larger studies on different ethnicities are recommended to validate the results.

Al-hijamah (the triple S treatment of prophetic medicine) significantly increases CD4/CD8 ratio in thalassemic patients via increasing TAC/MDA ratio: a clinical trial.

Beta thalassemia is associated with decreased immunity possibly due to iron overload. Al-hijamah (Hijamah) is wet cupping therapy (WCT) of prophetic medicine. Prophet Muhammad Peace be upon him said: "The best among your treatments is Al-hijamah". Al-hijamah is a promising excretory treatment to clear blood of causative pathological substances. Al-hijamah is a three-step technique (skin suction, scarification and suction) i.e. triple S technique). Recently, we introduced Al-hijamah as a novel iron excretion therapy (through pressure-dependent filtration then excretion via the skin dermal capillaries) that significantly decreased serum iron overload and related oxidative stress using a physiological excretory mechanism (Taibah mechanism). Iron overload was reported to impair both humoral immunity and cell mediated immunity in patients with beta thalassemia. In this study, twenty patients having ß-thalassemia major (maintained on iron chelation therapy) underwent a single session of Al-hijamah (30-60 minutes) using 4-5 sucking cups only. Another age and sex-matched control group of thalassemic patients received iron chelation therapy only. Al-hijamah enhanced the immunity of thalassemic patients in the form of increased CD4+ T cell count, from 124.10±36.98 to 326.20±57.94 cells/mm3, and an increased CD8+ T cell count from 100.30±36.98 to 272.40±46.37 cells/mm3. CD4/CD8 ratio significantly increased from 1.29 to 1.7 (P<0.001). There was a significant increase of ten times (P<0.001) in serum TAC/MDA ratio (reflects increased antioxidant capacity vs decreased oxidative load and stress) induced by Al-hijamah. After Al-hijamah, both CD4+ and CD8+ T cell counts significantly increased and positively correlated with TAC/MDA ratio (r = 0.246) and (r = 0.190), respectively. Moreover, CD4/CD8 ratio positively correlated with TAC/MDA after Al-hijamah (r = 0.285). In conclusion, Al-hijamah significantly increased CD4/CD8 ratio in thalassemic patients via increasing TAC/MDA ratio. Our study strongly recommends medical practice of Al-hijamah in hospitals for its immune potentiating effects in agreement with the evidence-based Taibah mechanism. Al-hijamah should be generalized for treating other immune-deficiency conditions. Al-hijamah-induced bloody excretion is so minimal and never aggravates the anaemic status.

The Preventive and Therapeutic Effects of Ajwa Date Fruit Extract Against Acute Diclofenac Toxicity-Induced Colopathy: An Experimental Study.

Background: Studies regarding treatment of acute toxicity with diclofenac (ATD) are quite few. Diclofenac is commonly prescribed in neurology, psychiatry, and general medicine practice. This study investigated possible colon-protective effects exerted by Ajwa date fruit extract (ADFE), a prophetic medicine remedy native to Al-Madinah, Saudi Arabia against ATD. Phytochemicals in ADFE as gallic acid and quercetin have reported protective effects against ATD. Methods: Total phenols and flavonoids in ADFE were estimated as equivalents to gallic acid and quercetin. Four experimental groups were allocated each of six rats: control group, ATD group received a single dose of 150 mg diclofenac intraperitoneally, toxicity prevention group received a single dose of ADFE orally followed 4 hours later by diclofenac injection, and toxicity treatment group received a similar diclofenac dose followed 4 hours later by a single dose of ADFE. Four days later, animals were sacrificed. Histological and biochemical examinations were done. Results: ADFE has a total phenolic content of 331.7 gallic acid equivalent/gram extract and a total flavonoid content of 70.23 quercetin equivalent/gram. ATD significantly increased oxidative stress markers as serum malondialdehyde (MDA) and hydrogen peroxide (H2O2). Serum MDA and H2O2 were significantly scavenged by ADFE. ATD significantly (p<0.001) decreased antioxidant power as serum total antioxidant capacity and catalase activity. That was reversed by ADFE in both prevention and treatment groups. Histologically, ATD caused complete destruction of colonic crypts architecture, patchy loss of the crypts, loss of the surface epithelium, absent goblet cells and submucosal exudate, heavy infiltration of the lamina propria and submucosa with inflammatory cells, mainly lymphocytes and eosinophils. There were mucosal haemorrhages and submucosal dilated congested blood vessels. All that was prevented and treated using ADFE. Conclusion: ADFE is rich in quercetin and gallic acid equivalents that exert potent antitoxic effects. ADFE is strongly recommended for preventive and therapeutic colon effects against ATD.

Impact of High Serum Levels of MMP-7, MMP-9, TGF-ß and PDGF Macrophage Activation Markers on Severity of COVID-19 in Obese-Diabetic Patients.

OBJECTIVE: The aim of this study was to identify an association between the severity of COVID-19 in obese-diabetic patients and altered serum levels of MMP-7, MMP-9, TGF-ß, and PDGF macrophage activation markers. METHODOLOGY: The study included 70 COVID-19 patients, divided into two groups: Group 1 included: Obese COVID-19 patients with type 2 diabetes mellitus (T2D, n=22 patients) and group 2 included; non-obese, non-diabetic COVID-19 patients as an age- and sex-matched control group (n=48 patients). Serum levels of the tested biomarkers were measured by ELISA at admission and after one weak follow-up. RESULTS: There was a significant reduction in the serum levels of LBP in obese-diabetic COVID-19 patients versus the control group (8.34±3.94 vs 20.78±7.61) (p 0.0001). Significant elevation of MMP-7, MMP-9, PDGF and TGF-ß was detected in obese diabetic COVID-19 patients compared to the non-obese non-diabetic group: 1044.7±519.6 vs 405.6±164.1, 483.05±46.5 vs 173.31±76.26, 154.5±62.78 vs 39.77±21.52, and 603.05±258.82 vs 180.29±97.17, respectively. The serum levels of macrophage activation markers in obese-diabetic patients one week after admission revealed that patients with acute respiratory distress syndrome (ARDS) had significantly higher serum levels of MMP-7 and MMP-9 than non-ARDS patients (p 0.02 and p 0.01 respectively). CONCLUSION: Macrophages were mainly polarized towards the M2 phenotype in obese-diabetic COVID-19 patients with significant upregulation of the pro-fibrotic markers MMP-7, MMP-9, PDGF, and TGF-ß. Thus, high levels of MMP-7 and MMP-9 are associated with ARDS in severe COVID-19 disease among obese-diabetic patients.

Evaluation of sTREM1 and suPAR Biomarkers as Diagnostic and Prognostic Predictors in Sepsis Patients.

BACKGROUND: The purpose of this study was to explore the diagnostic role of sTREM1 in the diagnosis of sepsis and in differentiating between sepsis and systemic inflammatory response syndrome (SIRS). We also aimed to assess the prognostic value of suPAR in comparison to sequential organ-failure assessment (SOFA), acute physiology and chronic health evaluation (APACHE) II scores, and 28-day mortality. METHODS: This was a cross-sectional study conducted in the Medical Microbiology and Immunology Department and Central Research Laboratory, Faculty of Medicine, Sohag University from June 2019 to January 2021. The study population was classified into two groups: SIRS (no evidence of infection) and sepsis (with SIRS and evidence of infection). Patients were rated on the SOFA and APACHE II scoring systems at admission and after 7 days. Serum levels of sTREM1 and suPAR were measured by ELISA at the same time points. RESULTS: CRP and sTREM1 values were significantly higher in the sepsis group than the SIRS group on both days (P<0.0001). The area under the curve (AUC) for CRP was 0.87 on the first day and 0.97 on the seventh, while the AUC for sTREM1 was 1.00 and 0.93 on the first and seventh days, respectively. The sensitivity of sTREM1 was 100% and specificity 84% at a cutoff of 49 pg/mL. There was a significantly positive correlation between CRP and sTREM1 values (P<0.0001). On the seventh day, nonsurvivors had significantly higher serum levels of suPAR (median 4.9 ng/mL) than survivors (median 2.9 ng/mL; P<0.0001). Nonsurvivors also had significantly higher SOFA and APACHE II scores than survivors (P<0.0001 and P<0.0001, respectively). CONCLUSION: sTREM1 can be used as a good indicator for diagnosing sepsis in intensive care-unit patients. suPAR can also be used as a predictor of bad prognosis and poor survival at 7 days following admission.

Promising preventive and therapeutic effects of TaibUVID nutritional supplements for COVID-19 pandemic: towards better public prophylaxis and treatment (A retrospective study).

Adjuvant nutritional treatment is a commonly overlooked topic when treating lethal viral diseases as COVID-19 pandemic. We recently introduced TaibUVID nutritional supplements (nigella sativa, chamomile and natural honey) as adjuvants for COVID-19 contacts, patients and public prophylaxis. TaibUVID Forte adds costus, senna and fennel to TaibUVID. Meta-analyses and systematic reviews confirmed evidence-based therapeutic benefits of TaibUVID components in treating many human diseases e.g. diabetes mellitus and hypertension, common co-morbidities in COVID-19 patients. Double-blind clinical trials for treating COVID-19 patients with TaibUVID supplements were inapplicable. In this retrospective study in Egypt, COVID-19 patients and contacts knew TaibUVID via social media and voluntarily used them. 65% of COVID-19 patients (n = 13) received both pharmacological treatments and adjuvant TaibUVID nutritional supplements. 35% (n = 7) received TaibUVID only. Lymphopenia rapidly improved to lymphocytosis upon regular TaibUVID intake. TaibUVID nutritional supplements helped COVID-19 contacts' prophylaxis. 70% of COVID-19 contacts (n = 14) (on regular TaibUVID intake) did not get SARS-COV2 infection. 30% (n = 6) were not using TaibUVID regularly and got mild flu-like symptoms and upon using both TaibUVID and pharmacological treatments, all improved and got negative nasopharyngeal swabs PCR. COVID-19 contacts were mainly physicians (40%, n = 8) (dealing with COVID-19 patients daily) and members of physicians' families (45%). Main presentations reported by COVID-19 patients (n = 20) were cough (90%), fever (55%), anosmia (45%), taste loss (45%), sore throat (45%), respiratory difficulty (45%) and malaise (35%). TaibUVID inhalation therapy (nigella sativa/anthemis/costus solution nebulization) was used by 65% of COVID-19 patients (n = 13) and alleviated respiratory manifestations e.g. cough and respiratory difficulty and was life-saving in some cases. 70% of COVID-19 patients (n = 14) improved in 1-4 days, 25% (n = 5) improved in 5-10 days while 5% improved in more than 10 days. TaibUVID nutritional supplements were tolerable and significantly satisfactory (P<0.01). 81.25% of COVID-19 patients (n = 13) did not report side effects. 18.25% (n = 3) reported mild diarrhea, sweating and hyperglycemia (not confirmed to be due to TaibUVID supplements). 31.25% of patients (n = 5) were satisfied by 100% with TaibUVID nutritional supplements. 37.5% (n = 6) of patients were satisfied by 75%. In conclusion, TaibUVID nutritional supplements are recommended for public prophylaxis (to decrease emergence of new cases) and treatment in COVID-19 pandemic. Clinical trials and further investigations are recommended.

TaibUVID nutritional supplements help rapid cure of COVID-19 infection and rapid reversion to negative nasopharyngeal swab PCR: for better public prophylaxis and treatment of COVID-19 pandemic.

Public prophylaxis to decrease the emergence of new daily COVID-19 cases is vital. Adjuvant TaibUVID nutritional supplements are promising home-made or hospital-made supplements suggested for rapidly preventing and treating COVID-19 pandemic. We report here a 44 years old male physician who caught COVID-19 infection at hospital in Egypt with confirmed positive nasopharyngeal swab PCR. Ethical committee approval and informed patient's consent were gained before performing this study. Chest X-ray revealed increased bronchovascular markings. Close follow-up was done with no treatment given and he was sent for home isolation. Few days later, he developed progressive non-productive cough and a sense of difficult breathing with no associated fever or chest pain. An antitussive drug was given to him. The patient read about TaibUVID supplements from social media and started to feel improvement after TaibUVID inhalation therapy (using the heated solution of nigella sativa and chamomile five times a day). He also received a home-made TaibUVID nutritional supplement (nigella sativa, chamomile and natural honey) five times daily for four consecutive days. The next day, he was quite better with mild symptoms. Two days later, nasopharyngeal swab PCR was negative while other patients still had positive nasopharyngeal swabs. As few attacks of mild cough and breathing difficulty existed, he was admitted to hospital. A nasopharyngeal swab PCR was done for him again and the result was negative also. Blood gases were normal. He had lymphocytosis (possibly due to TaibUVID effects) that counteract lymphopenia seen in COVID-19 patients. Biochemical and hematological evaluation were quite normal apart from increased serum chloride and lactate dehydrogenase. There was a mild decrease in serum CO2 and alkaline phosphatase. Chest CT report revealed symmetrically inflated both lungs with non-specific focal nodular infiltrates (scattered in basal and medial lung segments) in left lower lobes with faint ground glass opacities. He was discharged home. Few days later, he was quite improved with no symptoms and returned to his work comfortably. In conclusion, TaibUVID nutritional supplements may be effective in rapidly changing the nasopharyngeal swab PCR from positive to negative. TaibUVID nutritional supplements are advisable as a natural, safe and effective prophylaxis to stop COVID-19 infectiousness, transmission and emergence of new cases. Clinical studies to investigate TaibUVID nutritional benefits are strongly recommended. TaibUVID may be promising and recommended for public prophylaxis to decrease emergence of new COVID-19 cases.

Al-hijamah (the triple S treatment of prophetic medicine) exerts cardioprotective, tissue-protective and immune potentiating effects in thalassemic children: a pilot clinical trial.

Thalassemia is a major health problem in affected children due to iron overload, increased oxidative stress, atherogenic lipid profile and tissue-damage. This study aims at investigating the cardioprotective and tissue-protective benefits of Al-hijamah and their impact on cell-mediated immunity for treating thalassemic children. This study aimed also at investigating the tissue-clearance principle of Taibah mechanism: whenever pathological substances are to be cleared from the human body, Al-hijamah is indicated. Al-hijamah was done to thalassemic children (15 males and 5 females having a mean age of 9.07 ± 4.26 years) using sterile disposable sets in a complete aseptic hospital environment. Prior ethical committee agreement (in addition to written patient's consents) was obtained from Tanta Faculty of Medicine, Egypt. Twenty thalassemic children received iron chelation therapy plus Al-hijamah for one session (30-60 minutes) versus an age and sex-matched thalassemic control group treated with iron chelation therapy only. Al-hijamah is a quite safe outpatient hematological procedure that significantly decreased serum cholesterol (from 129.75 ± 3.67 to 103.5 ± 4.18 mg/dl) and decreased serum triglycerides (from 109.25 ± 8.96 to 91.95 ± 7.22 mg/dl). Interestingly, Al-hijamah exerted significant tissue-protective effects (it decreased serum GPT from 98.65 ± 12.27 to 71.65 ± 32.78 U/L and serum GOT from 96.35 ± 14.33 to 69.35 ± 34.37 U/L). Al-hijamah-induced ferritin excretion caused decreased serum ferritin (high serum ferritin negatively correlated with cell mediated immunity). Al-hijamah exerted cardioprotective and tissue-protective and hypolipidemic effects. Al-hijamah decreased serum cholesterol and is cardioprotective for thalassemic patients as it protects against atherogenesis and atherosclerosis. Medical practice of Al-hijamah is strongly recommended in hospitals. Al-hijamah cleared blood significantly from causative pathological substances e.g. serum ferritin resulting in enhanced cell-mediated immunity (in agreement with the evidence-based Taibah mechanism).

Association of Autoimmune Regulator Gene Rs2075876 Variant, but Not Gene Expression with Alopecia Areata in Males: A Case-control Study.

Alopecia areata (AA) is a non-scarring hair loss of autoimmune etiology. The autoimmune regulator (AIRE) gene is believed to be an important driver in AA pathogenesis. Genetic variants can alter mRNA expression levels which may provoke an autoimmune response. A total of 337 males (97 AA patients and 240 controls) were enrolled in the current case-control study. On screening of the most frequent variants in the gene, rs2075876 (A/G) polymorphism in intron 5 was selected and genotyped using Real-Time PCR (polymerase chain reaction) technology. Additionally, circulatory AIRE expression levels were quantified by quantitative reverse-transcription PCR (qRT-PCR). Allelic discrimination analysis revealed GG genotype to be more frequent in patients (90.7% in AA compared to 32.5% in controls, p < .001). G variant conferred increased risk to alopecia under homozygote comparison (GG versus AA: OR = 16.1, 95%CI = 5.57-46.3), dominant model (GG+AG versus AA: OR = 7.24, 95%CI = 2.5-20.5), recessive model (GG versus AG+AA: OR = 20.3, 95%CI = 9.7-42.4), and allelic model (G versus A: OR = 11.6, 95%CI = 6.47-21.1). The expression levels of AIRE gene did not differ significantly between patients and controls and were not related to rs2075876 variant. In conclusion, the intronic variant (rs2075876) is suggested to be a potent susceptibility variant for AA development in the studied population.Abbreviations: AA: Alopecia areata; AIRE: Autoimmune Regulator; APECED: Autoimmune, Polyendocrinopathy Candidiasis Ectodermal Dystrophy; DLQI: Dermatology life quality index questionnaire; MIQE: Minimum information for publication of quantitative real-time PCR experiments; mTEC: Medullary thymic epithelial cells; PHD: Plant homeodomain; qRT-PCR: Quantitative reversetranscription-polymerase chain reaction; RA: Rheumatoid arthritis.