A bitter flavonoid gum from Dorema aucheri accelerate wound healing in rats: Involvement of Bax/HSP 70 and hydroxyprolin mechanisms.

BACKGROUND: Dorema aucheri gum (DAG) is a bitter flavonoid gum widely used for numerous medicinal purposes including wound recovery. The present work investigates the acute toxicity and wound-healing effects of DAG in excisional skin injury in rats. MATERIALS AND METHODS: Sprague Dawley rats (24) were clustered into four groups, each rat had a full-thickness excisional dorsal neck injury (2.00 cm) and addressed with 0.2 mL of the following treatments for 15 days: Group A (vehicle), rats addressed with normal saline; Group B, rats received intrasite gel; C and D, rats addressed with 250 and 500 mg/kg of DAG, respectively. RESULTS: The results revealed the absence of any toxic signs in rats who received oral dosages of 2 and 5 g/kg of DAG. Wound healing was significantly accelerated following DAG treatments indicated by smaller open areas and higher wound contraction percentages compared to vehicle rats. Histological evaluation revealed higher fibroblast formation, collagen deposition, and noticeably lower inflammatory cell infiltration in granulated skin tissues of DAG-addressed rats compared to vehicle rats. DAG treatment caused significant modulation of immunohistochemical proteins (decreased Bax and increased HSP 70) and inflammatory mediators (reduced TNF-α, IL-6, and magnified IL-10), which were significantly varied compared to vehicle rats. Moreover, topical DAG treatment led to significant upregulation of the hydroxyproline (HDX) (collagen) and antioxidant content. At the same time, decreased the lipid peroxidation (MDA) levels in healed tissues obtained from DAG-treated rats. CONCLUSION: The present wound contraction by DAG might be linked with the modulatory effect of its phytochemicals (polysaccharides, flavonoids, and phenolic) on the cellular mechanisms, which justify their folkloric use and provokes further investigation as therapeutic drug additives for wound contraction.

Trends of Coagulation Parameters in Human Immunodeficiency Virus Patients.

Background and Objectives: HIV disease is recognized to cause inconsistencies in coagulation via various pathways during infection. Some studies have indicated that HIV-infected patients are prone to developing thrombocytopenia, thrombosis, or autoantibodies that may cause difficulties in diagnosis. This study is intended to measure the trend of coagulation parameters in Sudanese patients with HIV. Materials and Methods: A cross-sectional study was carried out in patients with HIV admitted to the Sudan National AIDS Program (SNAP) from January 2018 to December 2019. Prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), D-dimer (DD), hemoglobin (HB), total lymphocyte count (TLC), platelet count (PLT), and a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13), were evaluated among HIV Sudanese patients. Results: Out of the 44 HIV patients included, 6 (13.6%) were found to have thrombotic thrombocytopenic purpura-like events and 12 (27.2%) had antiphospholipid antibodies, of whom 8 (66.6%) showed anticardiolipin antibody (1gG (75%) and IgM (25%)) and 4 showed lupus anticoagulants. The HB, TLC, and PLT values were found to be significantly lower in HIV patients than in control (p = 0.000, 0.000, and 0.050, respectively). The PT and ADAMTS13 values showed no significant difference between HIV patients and control (p = 0.613 and 0.266, respectively). The PTT, TT, and DD values were found to be augmented in HIV patients versus the control (p = 0.000). Conclusions: Thrombotic thrombocytopenic purpura-like events among HIV Sudanese patients were explored. In addition, antiphospholipid antibodies were strikingly seen in these patients. Additional research is anticipated to confirm these diagnoses.

Neuroprotective effects of trigonelline in kainic acid-induced epilepsy: Behavioral, biochemical, and functional insights.

Trigonelline, an alkaloid found in the seeds of Trigonella foenum-graecum L. (fenugreek), has been recognized for its potential in treating various diseases. Notably, trigonelline has demonstrated a neuroprotective impact by reducing intrasynaptosomal calcium levels, inhibiting the production of reactive oxygen species (ROS), and regulating cytokines. Kainic acid, an agonist of kainic acid receptors, is utilized for inducing temporal lobe epilepsy and is a common choice for establishing kainic acid-induced status epilepticus, a widely used epileptic model. The neuroprotective effect of trigonelline in the context of kainic acid-induced epilepsy remains unexplored. This study aimed to induce epilepsy by administering kainic acid (10 mg/kg, single subcutaneous dose) and subsequently evaluate the potential anti-epileptic effect of trigonelline (100 mg/kg, intraperitoneal administration for 14 days). Ethosuccimide (ETX) (187.5 mg/kg) served as the standard drug for comparison. The anti-epileptic effect of trigonelline over a 14-day administration period was examined. Behavioral assessments, such as the Novel Object Recognition (NOR) test, Open Field Test (OFT), and Plus Maze tests, were conducted 2 h after kainic acid administration to investigate spatial and non-spatial acquisition abilities in rats. Additionally, biochemical analysis encompassing intrasynaptosomal calcium levels, LDH activity, serotonin levels, oxidative indicators, and inflammatory cytokines associated with inflammation were evaluated. Trigonelline exhibited significant behavioral improvements by reducing anxiety in open field and plus maze tests, along with an amelioration of memory impairment. Notably, trigonelline substantially lowered intrasynaptosomal calcium levels and LDH activity, indicating its neuroprotective effect by mitigating cytotoxicity and neuronal injury within the hippocampus tissue. Moreover, trigonelline demonstrated a remarkable reduction in inflammatory cytokines and oxidative stress indicators. In summary, this study underscores the potential of trigonelline as an anti-epileptic agent in the context of kainic acid-induced epilepsy. The compound exhibited beneficial effects on behavior, neuroprotection, and inflammation, shedding light on its therapeutic promise for epilepsy management.

Mechanisms of anti-ulcer actions of Prangos pabularia (L.) in ethanol-induced gastric ulcer in rats.

Peptic ulcer disease is the greatest digestive disorder that has increased incidence and recurrence rates across all nations. Prangos pabularia (L.) has been well documented as a folkloric medicinal herb utilized for multiple disease conditions including gastric ulcers. Hence, the target study was investigation the gastro-protection effects of root extracts of Prangos pabularia (REPP) on ethanol-mediated stomach injury in rats. Sprague Dawley rats were clustered in 5 cages: A and B, normal and ulcer control rats pre-ingested with 1 % carboxymethyl cellulose (CMC)); C, reference rats had 20 mg/kg omeprazole; D and E, rats pre-supplemented with 250 and 500 mg/kg of REPP, respectively. After one hour, group A was given orally 1 % CMC, and groups B-E were given 100 % ethanol. The ulcer area, gastric acidity, and gastric wall mucus of all stomachs were determined. The gastric tissue homogenates were examined for antioxidant and MDA contents. Moreover, the gastric tissues were analyzed by histopathological and immunohistochemically assays. Acute toxicity results showed lack of any toxic effects or histological changes in rats exposed to 2 and 5 g/kg of REPP ingestion. The ulcer controls had extensive gastric mucosal damage with lower gastric juice and a reduced gastric pH. REPP treatment caused a significant reduction of the ethanol-induced gastric lacerations represented by an upsurge in gastric mucus and gastric wall glycoproteins (increased PAS), a decrease in the gastric acidity, leukocyte infiltration, positively modulated Bax and HSP 70 proteins, consequently lowered ulcer areas. REPP supplementation positively modulated oxidative stress (increased SOD, CAT, PGE2, and reduced MDA) and inflammatory cytokines (decreased serum TNF-α, IL-6, and increased IL-10) levels. The outcomes could be scientific evidence to back-up the folkloric use of A. Judaica as a medicinal remedy for oxidative stress-related disorders (gastric ulcer).

In-vitro and in-silico evaluation of rue herb for SARS-CoV-2 treatment.

SARS-CoV-2, a ß-coronavirus responsible for the COVID-19 pandemic, has resulted in approximately 4.9 million fatalities worldwide. Despite the urgent need, there is currently no specific therapeutic developed for treating or preventing SARS-CoV-2 infections. The virus enters the host by engaging in a molecular interaction between the viral Spike glycoprotein (S protein) and the host ACE2 receptor, facilitating membrane fusion and initiating infection. Inhibiting this interaction could impede viral activity. Therefore, this study aimed to identify natural small molecules from perennial rue herb (Ruta graveolens) as potential inhibitors against the S protein, thus preventing virus infection. Initially, a screening process was conducted on 53 compounds identified from rue herbs, utilizing pharmacophore-based virtual screening approaches. This analysis resulted in the identification of 12 hit compounds. Four compounds, namely Amentoflavone (CID: 5281600), Agathisflavone (CID: 5281599), Vitamin P (CID: 24832108), and Daphnoretin (CID: 5281406), emerged as potential S protein inhibitors through molecular docking simulations, exhibiting binding energies in kcal/mol of -9.2, -8.8, -8.2, and -8.0, respectively. ADMET analysis revealed favorable pharmacokinetics and toxicity profiles for these compounds. The compounds' stability with respect to the target S protein was evaluated using MD simulation and MM-GBSA approaches. The analysis revealed the stability of the selected compounds with the target protein. Also, PCA revealed distinctive movement patterns in four selected compounds, offered valuable insights into their functional behaviors and potential interactions. In-vitro assays revealed that rue herb extracts containing these compounds displayed potential inhibitory properties against the virus, with an IC50 value of 1.299 mg/mL and a cytotoxic concentration (CC50) value of 11.991 mg/mL. The compounds derived from rue herb, specifically Amentoflavone, Agathisflavone, Vitamin P, and Daphnoretin, show promise as candidates for the therapeutic intervention of SARS-CoV-2-related complications.

Sinomenine accelerate wound healing in rats by augmentation of antioxidant, anti-inflammatory, immunuhistochemical pathways.

Sinomenine (SN) is a well-documented unique plant alkaloid extracted from many herbal medicines. The present study evaluates the wound healing potentials of SN on dorsal neck injury in rats. A uniform cut was created on Sprague Dawley rats (24) which were arbitrarily aligned into 4 groups receiving two daily topical treatments for 14 days as follows: A, rats had gum acacia; B, rats addressed with intrasite gel; C and D, rats had 30 and 60 mg/ml of SN, respectively. The acute toxicity trial revealed the absence of any toxic signs in rats after two weeks of ingestion of 30 and 300 mg/kg of SN. SN-treated rats showed smaller wound areas and higher wound closure percentages compared to vehicle rats after 5, 10, and 15 days of skin excision. Histological evaluation of recovered wound tissues showed increased collagen deposition, fibroblast content, and decreased inflammatory cells in granulated tissues in SN-addressed rats, which were statistically different from that of gum acacia-treated rats. SN treatment caused positive augmentation of Transforming Growth Factor Beta 1 (angiogenetic factor) in wound tissues, denoting a higher conversion rate of fibroblast into myofibroblast (angiogenesis) that results in faster wound healing action. Increased antioxidant enzymes (SOD and CAT), as well as decreased MDA contents in recovered wound tissues of SN-treated rats, suggest the antioxidant potentials of SN that aid in faster wound recovery. Wound tissue homogenates showed higher hydroxyproline amino acid (collagen content) values in SN-treated rats than in vehicle rats. SN treatment suppressed the production of pro-inflammatory cytokines and increased anti-inflammatory cytokines in the serum of wounded rats. The outcomes present SN as a viable pharmaceutical agent for wound healing evidenced by its positive modulation of the antioxidant, immunohistochemically proteins, hydroxyproline, and anti-inflammatory cytokines.

Wood calamint ameliorates ethanol-induced stomach injury in rats by augmentation of hsp/bax and inflammatory mechanisms.

Clinopodium menthifolium (wood calamint) is a folkloric medicinal plant ingested as a treatment for many human disorders including gastric disorders. Our study evaluates the anti-ulcer potentials of Clinopodium menthifolium ethanol extracts (CMEE) in induced gastric ulcers in rats. Thirty Dawley male rats were divided into 5 groups: normal and ulcer controls, treated orally with Tween 20%; reference rats treated with Omeprazole 20 mg/kg, and the remaining two groups received 250 and 500 mg/kg CMEE for 2 weeks. After that, food was taken away for 24 h, and then, rats received ethanol-induced gastric ulceration (except normal control), 80% (1 ml/rat). After anesthetization and sacrificing, the ulcer index, mucus content, and other ulcer measurements were obtained from dissected rat stomachs. Stomach tissues were also analyzed by different histology procedures and homogenized stomach tissues were assessed for their antioxidant contents. The toxicity trial showed the absence of any toxic signs in rats supplemented with 2 and 5 g/kg of CMEE. The gastroprotective results showed a significantly lower ulcer index and higher gastric mucin content in CMEE-ingested rats compared to ulcer controls. Furthermore, CMEE treatments significantly increased the intensity of periodic acid Schiff stained (PAS), HSP 70 protein, and down-regulation of Bax protein expression in the stomach epithelium. Rats supplemented with 500 mg/kg revealed noticeable changes in their serum inflammatory cytokines along with positive regulations of antioxidant enzymes. The outcomes provide a scientific backup behind the gastroprotective potential effect of CMEE that could serve as a natural resource against peptic ulcers.

A triterpenoid (corosolic acid) ameliorated AOM-mediated aberrant crypt foci in rats: modulation of Bax/PCNA, antioxidant and inflammatory mechanisms.

Corosolic acid (CA) is a well-known natural pentacyclic triterpene found in numerous therapeutic plants that can exhibit many bioactivities including anti-inflammatory and anti-tumor actions. The current investigation explores the chemoprotective roles of CA against azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Thirty Sprague Dawley rats were grouped in 5 cages; Group A, normal control rats inoculated subcutaneously (sc) with two doses of normal saline and fed orally on 10% tween 20; Groups B-E received two doses (sc) of azoxymethane in two weeks and treated with either 10% tween 20 (group B) or two intraperitoneal injections of 35 mg/kg 5-fluorouracil each week for one month (group C), while group D and E treated with 30 and 60 mg/kg, respectively, for 2 months. The toxicity results showed lack of any behavioral abnormalities or mortality in rats ingested with up-to 500 mg/kg of CA. The present AOM induction caused a significant initiation of ACF characterized by an increased number, larger in size, and well-matured tissue clusters in cancer controls. AOM inoculation created a bizarrely elongated nucleus, and strained cells, and significantly lowered the submucosal glands in colon tissues of cancer controls compared to 5-FU or CA-treated rats. CA treatment led to significant suppression of ACF incidence, which could be mediated by its modulatory effects on the immunohistochemical proteins (pro-apoptotic (Bax) and reduced PCNA protein expressions in colon tissues). Moreover, CA-treated rats had improved oxidative stress-mediated cytotoxicity indicated by increased endogenous antioxidants (SOD and CAT) and reduced lipid peroxidation indicators (MDA). In addition, CA ingestion (30 and 60 mg/kg) suppressed the inflammatory cascades, indicated by decreased serum TNF-α and IL-6 cytokines and increased anti-inflammatory (IL-10) cytokines consequently preventing further tumor development. CA treatment maintained liver and kidney functions in rats exposed to AOM cytotoxicity. CA could be a viable alternative for the treatment of oxidative-related human disorders including ACF.

The Association of Human Leukocyte Antigens Complex with Type 1 Diabetes in the Omani Population.

Objectives: Identification of the high risk alleles, genotypes and haplotypes of the human leukocyte antigens (HLA) in different populations is beneficial for understanding their roles in type 1 diabetes (T1D) pathogenesis and intervention practices. This study aimed to identify T1D-associated HLA gene alleles in the Omani population. Methods: The present case-control study included 73 diabetic seropositive children (mean age 9.08 ± 3.27 years) attending the paediatric clinic at Sultan Qaboos University Hospital in Muscat, Oman, and 110 healthy controls. HLA-A, -B, -C, -DRB1 and -DQB1 genes were genotyped using a sequence-specific primer polymerase chain reaction (SSP-PCR). Results: Two HLA class I alleles (B*08, B*58) and three class II alleles (DQB1*02, DRB1*03 and DRB1*04) were associated with T1D susceptibility, while one class I (B*51) and three class II (DQB1*05, DQB1*06 and DRB1*16) alleles were associated with T1D protection. HLA-DRB1*03 and DQB1*02 alleles showed the strongest risk association among all alleles. Six DRB1 residues (E9, S11, S13, Y30, V70 and K71) were significantly associated with T1D susceptibility. Heterozygous genotypes, HLA-DRB1*03/*04 and DQB1*02/*03 were significantly associated with T1D susceptibility (P <0.0001, odds ratio [OR] = 63.21 and P = 0.02, OR = 3.63, respectively). Furthermore, a significant combined action of DRB1*03-DQB1*02 haplotype in T1D risk (P = 0.000176, OR = 15) and DRB1*16-DQB1*05 haplotype in protection (P = 0.0312, OR = 0.48) was detected. Conclusion: Known HLA class II gene alleles are associated with T1D in Omani children.

QbD Design, Formulation, Optimization and Evaluation of Trans-Tympanic Reverse Gelatination Gel of Norfloxacin: Investigating Gene-Gene Interactions to Enhance Therapeutic Efficacy.

Traditional otic drug delivery methods lack controlled release capabilities, making reverse gelatination gels a promising alternative. Reverse gelatination gels are colloidal systems that transition from a sol to a gel phase at the target site, providing controlled drug release over an extended period. Thermosensitive norfloxacin reverse gelatination gels were developed using a Quality by Design (QbD)-based optimization approach. The formulations were evaluated for their in vitro release profile, rheological behavior, visual appearance, pH, gelling time, and sol-gel transition temperature. The results show that the gelation temperatures of the formulations ranged from 33 to 37 °C, with gelling durations between 35 and 90 s. The drug content in the formulations was uniform, with entrapment efficiency ranging from 55% to 95%. Among the formulations, F10 exhibited the most favorable properties and was selected for a stability study lasting 60 days. Ex-vivo release data demonstrate that the F10 formulation achieved 95.6percentage of drug release at 360 min. This study successfully developed thermosensitive norfloxacin reverse gelatination gels using a QbD-based optimization approach. The selected formulation, F10, exhibited desirable properties in terms of gelling temperature, drug content, and release profile. These gels hold potential for the controlled delivery of norfloxacin in the treatment of ear infections.

Antimicrobial, antioxidant and cytotoxic activities and phytochemical screening of some yemeni medicinal plants.

The traditional medicine still plays an important role in the primary health care in Yemen. The current study represents the investigation of 16 selected plants, which were collected from different localities of Yemen. The plants were dried and extracted with two different solvents (methanol and hot water) to yield 34 crude extracts. The obtained extracts were tested for their antimicrobial activity against three Gram-positive bacteria, two Gram-negative bacteria, one yeast species and three multiresistant Staphylococcus strains using agar diffusion method, for their antioxidant activity using scavenging activity of DPPH radical method and for their cytotoxic activity using the neutral red uptake assay. In addition, a phytochemical screening of the methanolic extracts was done. Antibacterial activity was shown only against Gram-positive bacteria, among them multiresistant bacteria. The highest antimicrobial activity was exhibited by the methanolic extracts of Acalypha fruticosa, Centaurea pseudosinaica, Dodonaea viscosa, Jatropha variegata, Lippia citriodora, Plectranthus hadiensis, Tragia pungens and Verbascum bottae. Six methanolic extracts especially those of A. fruticosa, Actiniopteris semiflabellata, D. viscosa, P. hadiensis, T. pungens and V. bottae showed high free radical scavenging activity. Moreover, remarkable cytotoxic activity against FL-cells was found for the methanolic extracts of A. fruticosa, Iris albicans, L. citriodora and T. pungens. The phytochemical screening demonstrated the presence of different types of compounds like flavonoids, terpenoids and others, which could be responsible for the obtained activities.

Correction: Frankincense essential oil suppresses melanoma cancer through down regulation of Bcl-2/Bax cascade signaling and ameliorates heptotoxicity via phase I and II drug metabolizing enzymes.

[This corrects the article DOI: 10.18632/oncotarget.26930.].

Frankincense essential oil suppresses melanoma cancer through down regulation of Bcl-2/Bax cascade signaling and ameliorates heptotoxicity via phase I and II drug metabolizing enzymes.

Melanoma is a deadly form of malignancy and according to the World Health Organization 132,000 new cases of melanoma are diagnosed worldwide each year. Surgical resection and chemo/drug treatments opted for early and late stage of melanoma respectively, however detrimental post surgical and chemotherapy consequences are inevitable. Noticeably melanoma drug treatments are associated with liver injuries such as hepatitis and cholestasis which are very common. Alleviation of these clinical manifestations with better treatment options would enhance prognosis status and patients survival. Natural products which induce cytotoxicity with minimum side effects are of interest to achieve high therapeutic efficiency. In this study we investigated anti-melanoma and hepatoprotective activities of frankincense essential oil (FEO) in both in vitro and in vivo models. Pretreatment with FEO induce a significant (p < 0.05) dose-dependent reduction in the cell viability of mouse (B16-F10) and human melanoma (FM94) but not in the normal human epithelial melanocytes (HNEM). Immunoblot analysis showed that FEO induces down regulation of Bcl-2 and up regulation of BAX in B16-F10 cells whereas in FM94 cells FEO induced dose-dependent cleavage of caspase 3, caspase 9 and PARP. Furthermore, FEO (10 µg/ml) treatment down regulated MCL1 in a time-dependent manner in FM94 cells. In vivo toxicity analysis reveals that weekly single dose of FEO (1200 mg/kg body weight) did not elicit detrimental effect on body weight during four weeks of experimental period. Histology of tissue sections also indicated that there were no observable histopathologic differences in the brain, heart, liver, and kidney compare to control groups. FEO (300 and 600 mg/kg body weight) treatments significantly reduced the tumor burden in C57BL/6 mice melanoma model. Acetaminophen (750 mg/kg body weight) was used to induce hepatic injury in Swiss albino mice. Pre treatment with FEO (250 and 500 mg/kg body weight) for seven days retained hematology (complete blood count), biochemical parameters (AST, ALT, ALK, total bilirubin, total protein, glucose, albumin/globulin ratio, cholesterol and triglyceride), and the level of phase I and II drug metabolizing enzymes (cytochrome P450, cytochromeb5, glutathione-S-transferase) which were obstructed by the administration of acetaminophen. Further liver histology showed that FEO treatments reversed the damages (central vein dilation, hemorrhage, and nuclei condensation) caused by acetaminophen. In conclusion, FEO elicited marked anti-melanoma in both in vitro and in vivo with a significant heptoprotection.

Induction of HT-29 Colon Cancer Cells Apoptosis by Pyrogallol with Growth Inhibiting Efficacy Against Drug-Resistant Helicobacter pylori.

BACKGROUND: Colon cancer is the most aggressive form of cancers, that causes 0.5 million deaths per year around the globe. Targeting colon cancer by conventional therapeutic options elicits toxicity. Traditional medicines take a lead to alleviate the existing clinical challenges. OBJECTIVE: To investigate antibacterial activity against Helicobacter Pylori and in vitro anti-colon cancer activity by Acacia nilotica extract (ACE) and its active constituent pyrogallol. METHODS: Pyrogallol isolated from A. nilotica by column chromatography and HPLC and structure was elucidated by spectral analysis. Antibacterial activity was done by flow cytometry. Cytotoxicity was measured by MTT assay. Apoptotic morphology and nuclear fragmentation were assessed with AO/ethidium bromide and DAPI staining. DNA fragmentation was done by electrophoresis. Western blot used to analyze the molecular mechanism of apoptosis. Cell cycle arrest was determined using flow cytometry of propidium iodide stained cells. Cell migration was determined by wound healing assay. RESULTS: ACE (20 µg/ml) and pyrogallol (10 µg/ml) treatment reduced the survival of H.pylori at 61% and 62%, respectively. MTT results show that HT-29 cells are more sensitive to pyrogallol with an IC50 value of 35µg/ml compared to ACE. Pyrogallol treated HT-29 cells reached dead state i.e. late apoptotic state with severe nuclear fragmentation. Pyrogallol elicits dose dependent DNA fragmentation in HT-29 cells. Pyrogallol induced apoptosis by simultaneous down-regulation of Bcl-2 and up-regulation of BAX and cytochrome c. Pyrogallol arrested HT-29 cells in S and G2/M phase of cell cycle. Further pyrogallol exhibited marked antimetastatic potential by inhibiting the migration of HT-29 cells dose dependently. CONCLUSION: Both ACE and pyrogallol repressed the growth of H.pylori and as significant anti-colon cancer agent.

Altered blood cytokines, CD4 T cells, NK and neutrophils in patients with obstructive sleep apnea.

BACKGROUND: There are contradictory reports on the effects of obstructive sleep apnea (OSA) on the immune system. In order to clarify the effect of OSA on the different components of the immune system, we studied the association of OSA with changes in cytokine and chemokine levels, proliferative patterns of CD4 and CD8 T lymphocytes as well as NK cells ex vivo and neutrophil functions. METHODS: We investigated the association of OSA with potential alterations in 14 Th1/Th2 and inflammatory cytokines and chemokines, CD4 and CD8 T cells, NK cells, and the NADPH oxidase activation and phagocytic functions in neutrophils. RESULTS: Our results suggest that the increase in CD4 T cell frequency in OSA is associated with an increased expression of the nuclear protein Ki67 (p<0.05; power>0.8), and is correlated with the levels of IL-1ß (p<0.05; power>0.8). The levels of IL-1ß as well as IL-6 showed a potential increase, while the levels of IFN-γ (p<0.05; power>0.8) and the ratio IFN-γ/IL-4 in the blood were possibly decreased in OSA. Additionally, we observed a potential increase in the expression of Ki67 in CD8hi and CD8lo NK cells (p<0.05; power>0.8). Our results also suggest that neutrophils have a decreased capacity to phagocytose bacteria and activate NADPH oxidase in OSA patients (p<0.05; power>0.8). CONCLUSION: OSA may be associated with inflammatory and pro-Th2 immune responses, an increased proliferative potential of NK and CD4 T cells and a decreased capacity of neutrophils to phagocytose bacteria and produce ROS.

HLA-A68 and HLA-B15 alleles correlate with poor immune response among AIDS patients on combined antiretroviral therapy.

Around 15-30% of AIDS patients fail to recover their CD4(+) T cell levels following combined antiretroviral therapy despite successful inhibition of HIV-1 replication. The exact reasons for this immune recovery failure are not completely understood. HLA alleles are among the candidate that may explain this failure. A total of 65 adult AIDS patients, with viral load of <50 copies per ml were investigated. Viral load and CD4 T cells counts were performed following standard techniques. HLA genotyping was performed using PCR-SSP technique. The Statistical Package for Social Sciences (SPSS version 19) was used for data processing and analysis. A significantly higher proportion of poor immune responders were carrying HLA-A68 (4.8% compared to 25.0%, P=0.025) and HLA-B15 (2.4% compared to 20.8%, P=0.023). The etiological fraction (Efe%) among carriers of HLA-A68 was 57.89% (95% CI=26.79, 75.79) and was 61.35% (95% CI=35.33, 76.91) among carriers of HLA-B15.

High Levels of IgA Antibodies to Helicobacter Pylori among Omani Women during Pregnancy and after Delivery.

BACKGROUND: Helicobacter pylori (H. pylori), is a common infection in pregnant women accompanied by variations in the levels of the IgM, IgA and IgG antibody isotypes. The variations of anti-H. pylori antibodies during and after pregnancy, and the extent of protection they provide to the mother and the fetus are not completely understood. OBJECTIVES: To investigate the changes of the anti-H. pylori IgM, IgA and IgG levels in healthy Omani pregnant women during pregnancy and 3 months after delivery. METHODS: Serum samples obtained from 70 Omani healthy pregnant women, with no history of autoimmune diseases, were tested for anti-H. pylori IgM, IgA and IgG in the first trimester of pregnancy and 3 months after delivery. In parallel and as a control group, sera obtained from a group of 70 healthy non-pregnant Omani women were tested. The levels of anti-H. pylori IgM, IgA and IgG were measured using standard Enzyme Linked Immunosorbent Assays (ELISAs). RESULTS: Anti-H. pylori IgA levels were found to be significantly higher during pregnancy (p=0.046) and after delivery (p=0.02) when compared to the control group. Moreover, a significant increase in the levels of anti-H. pylori IgM, IgA and IgG was detected after delivery (p=0.002) when compared to the levels during pregnancy. CONCLUSION: Pregnancy is associated with an increase in the levels of anti-H. pylori IgA antibodies. In addition, anti-H. pylori IgM, IgG and IgA antibody levels increase after delivery.

In Vitro Apoptosis Triggering in the BT-474 Human Breast Cancer Cell Line by Lyophilised Camel's Milk.

Breast cancer is a global health concern and is a major cause of death among women. In Oman, it is the most common cancer in women, with an incidence rate of 15.6 per 100,000 Omani females. Various anticancer remedies have been discovered from natural products in the past and the search is continuing for additional examples. Cytotoxic natural compounds may have a major role in cancer therapy either in potentiating the effect of chemotherapy or reducing its harmful effects. Recently, a few studies have reported advantages of using crude camel milk in treating some forms of cancer. However, no adequate data are available on the lyophilised camel's milk responsibility for triggering apoptosis and oxidative stress associated with human breast cancer. The present study aimed to address the role of the lyophilised camel's milk in inducing proliferation repression of BT-474 and HEp-2 cells compared with the non-cancer HCC1937 BL cell line. Lyophilized camel's milk fundamentally repressed BT-474 cells growth and proliferation through the initiation of either the intrinsic and extrinsic apoptotic pathways as indicated by both caspase-3 mRNA and its action level, and induction of death receptors in BT-474 but not the HEp-2 cell line. In addition, lyophilised camel's milk enhanced the expression of oxidative stress markers, heme-oxygenase-1 and reactive oxygen species production in BT-474 cells. Increase in caspase-3 mRNA levels by the lyophilised camel's milk was completely prevented by the actinomycin D, a transcriptional inhibitor. This suggests that lyophilized camel's milk increased newly synthesized RNA. Interestingly,it significantly (p<0.003) repressed the growth of HEp-2 cells and BT-474 cells after treatment for 72 hours while 24 hours treatment repressed BT-474 cells alone. This finding suggests that the lyophilised camel's milk might instigate apoptosis through initiation of an alternative apoptotic pathway.

High levels of Zinc-α-2-Glycoprotein among Omani AIDS patients on combined antiretroviral therapy.

OBJECTIVE: To investigate the levels of zinc-α-2-glycoprotein (ZAG) among Omani AIDS patients receiving combined antiretroviral therapy (cART). METHODS: A total of 80 Omani AIDS patients (45 males and 35 females), average age of 36 years, who were receiving cART at the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, were tested for the levels of ZAG. In addition, 80 healthy blood donors (46 males and 34 females), average age of 26 years, attending the SQUH Blood Bank, were tested in parallel as a control group. Measurement of the ZAG levels was performed using a competitive enzyme-linked immunosorbent assay and in accordance with the manufacturer's instructions. RESULTS: The ZAG levels were found to be significantly higher among AIDS patients compared to the healthy individuals (P=0.033). A total of 56 (70%) of the AIDS patients were found to have higher levels of ZAG and 16 (20%) AIDS patients were found to have high ZAG levels, which are significantly (P>0.031) associated with weight loss. CONCLUSIONS: ZAG levels are high among Omani AIDS patients on cART and this necessitates the measurement of ZAG on routine basis, as it is associated with weight loss.

Fluctuation in the Levels of Immunoglobulin M and Immunoglobulin G Antibodies for Cardiolipin and ß2-Glycoprotein among Healthy Pregnant Women.

OBJECTIVES: Antiphospholipid antibodies fluctuate during a healthy normal pregnancy. This study aimed to investigate the levels of both immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies for cardiolipin and ß2-glycoprotein (ß2GP) among healthy pregnant women. METHODS: This study was conducted between May 2010 and December 2012. A total of 75 healthy Omani pregnant women with no history of autoimmune disease were investigated during their pregnancy and 90 days after delivery at the Armed Forces Hospital in Muscat, Oman. A control group of 75 healthy Omani non-pregnant women were also investigated as a comparison. Levels of IgM and IgG antibodies for both anti-cardiolipin antibodies (ACAs) and ß2GP were measured using a standard enzyme-linked immunosorbent assay. RESULTS: The ACA IgM levels were significantly higher in the control group compared to the pregnant women (P <0.001). No significant differences were observed in the ACA IgM levels between the control group and the pregnant women after delivery. In contrast, ACA IgG levels were significantly higher during pregnancy and after delivery compared with those of the healthy control group (P = 0.007 and 0.002, respectively). The levels of ß2GP IgG were significantly higher during pregnancy than after delivery and in the control group (P = 0.001 and <0.001, respectively). CONCLUSION: In this study, ACA IgG levels increased during healthy pregnancies and after normal deliveries whereas ß2GP IgG levels increased transiently during the pregnancies. Both phenomena were found to be significantly associated with a transient decline in the levels of IgM specific for these antigens. Therefore, the levels of these antibodies may be regulated during a healthy pregnancy.