Identification of two novel FUT1 mutations in people with Bombay phenotype from Iran.

BACKGROUND AND PURPOSE: Bombay and Para-Bombay phenotypes are characterized by FUT1 gene mutation and lack of H antigen expression in red blood cells. ABH antigens are not present in the body secretions of Bombay individuals, while they are expressed in the secretions of para-Bombay. The aim of this study was to investigate the molecular basis of FUT1 and FUT2 genes in Iranians with the Bombay or Para-Bombay phenotype. MATERIALS AND METHODS: ABO phenotype analysis and routine serological tests were performed on 11 people with Bombay and Para-Bombay phenotypes. The coding regions of FUT1 and FUT2 genes were amplified by PCR followed by sequencing. The ABO genotypes were also determined by sequencing exons 6 and 7 of the ABO gene. RESULTS: Serological investigations confirmed the Bombay phenotype in 8 samples and the Para-Bombay phenotype in 3 samples. Family members with the Bombay phenotype had the classic c 0.725 T > G mutation in the FUT1 gene, accompanied by deletion of the FUT2 gene. Other samples had c.653 A>G, c 0.661 C>T, c 0.652 C>G, and c.722 A>C mutations in the FUT1 while FUT2 was silenced by c 0.461 G>A. CONCLUSION: In this research, we identified two novel mutations in the FUT1 gene in individuals with the Bombay phenotype. This and previous works confirm the variety of FUT1 mutations.

(E)-2-Benzylidenecyclanones: Part XVIII Study the Possible Link between Glutathione Reactivity and Cancer Cell Cytotoxic Effects of Some Cyclic Chalcone Analogs A Comparison of the Reactivity of the Open-Chain and the Seven-Membered Homologs.

Non-enzymatic thiol addition into the α,ß-unsaturated carbonyl system is associated with several biological effects. In vivo, the reactions can form small-molecule thiol (e.g., glutathione) or protein thiol adducts. The reaction of two synthetic (4'-methyl- and 4'-methoxy substituted) cyclic chalcone analogs with reduced glutathione (GSH) and N-acetylcysteine (NAC) was studied by (high-pressure liquid chromatography-ultraviolet spectroscopy) HPLC-UV method. The selected compounds displayed in vitro cancer cell cytotoxicity (IC50) of different orders of magnitude. The structure of the formed adducts was confirmed by (high-pressure liquid chromatography-mass spectrometry) HPLC-MS. The incubations were performed under three different pH conditions (pH 3.2/3.7, 6.3/6.8, and 8.0/7.4). The chalcones intrinsically reacted with both thiols under all incubation conditions. The initial rates and compositions of the final mixtures depended on the substitution and the pH. The frontier molecular orbitals and the Fukui function were carried out to investigate the effects on open-chain and seven-membered cyclic analogs. Furthermore, machine learning protocols were used to provide more insights into physicochemical properties and to support the different thiol-reactivity. HPLC analysis indicated diastereoselectivity of the reactions. The observed reactivities do not directly relate to the different in vitro cancer cell cytotoxicity of the compounds.

Reaction of Chalcones with Cellular Thiols. The Effect of the 4-Substitution of Chalcones and Protonation State of the Thiols on the Addition Process. Diastereoselective Thiol Addition.

Several biological effects of chalcones have been reported to be associated with their thiol reactivity. In vivo, the reactions can result in the formation of small-molecule or protein thiol adducts. Both types of reactions can play a role in the biological effects of this class of compounds. Progress of the reaction of 4-methyl- and 4-methoxychalcone with glutathione and N-acetylcysteine was studied by the HPLC-UV-VIS method. The reactions were conducted under three different pH conditions. HPLC-MS measurements confirmed the structure of the formed adducts. The chalcones reacted with both thiols under all incubation conditions. The initial rate and composition of the equilibrium mixtures depended on the ratio of the deprotonated form of the thiols. In the reaction of 4-methoxychalcone with N-acetylcysteine under strongly basic conditions, transformation of the kinetic adduct into the thermodynamically more stable one was observed. Addition of S-protonated N-acetylcysteine onto the polar double bonds of the chalcones showed different degrees of diastereoselectivity. Both chalcones showed a Michael-type addition reaction with the ionized and non-ionized forms of the investigated thiols. The initial reactivity of the chalcones and the equilibrium composition of the incubates showed a positive correlation with the degree of ionization of the thiols. Conversions showed systematic differences under each set of conditions. The observed differences can hint at the difference in reported biological actions of 4-methyl- and 4-methoxy-substituted chalcones.

Some of the effective factors in the pathogenesis of gastro-oesophageal reflux disease.

Oesophageal adenocarcinoma is one of the most fatal tumours to affect the digestive tract and is the eighth most common malignancy worldwide. Gastro-oesophageal reflux has an important role in the incidence of adenocarcinoma of the oesophagus. Gastro-oesophageal reflux disease (GERD) is a multifactorial, acid-peptic disorder that results from the reflux of noxious material from the stomach into the oesophagus. The refluxed material causes the occurrence of oesophageal inflammation which creates a condition that is called reflux oesophagitis. The prevalence of this disease has increased dramatically in recent decades, mostly in the western world, where it affects about 10% to 30% of the population. The aetiology of oesophageal mucosal damage is complicated. Many inflammatory mediators are produced within the gastrointestinal (GI) tract, but their contributions in pathophysiology and disease pathogenesis have not been well investigated. Despite the protective barrier provided by the oesophageal mucosa, refluxed materials can cause oxidative injury and in?ammatory responses that involve the epithelium and immune cells. The analysing cellular events in gastro- oesophageal reflux disease and physiological responses to such conditions are important and necessary for a better grasp of the pathogenesis of GERD and the expansion of new treatments. Therefore, we want to discuss some of the important and key factors of GERD disease in this article.

The effect of temperature and storage time on DNA integrity after freeze-drying sperm from individuals with normozoospermia.

OBJECTIVE: This study evaluated the effects of temperature and storage time on the quality and DNA integrity of freeze-dried sperm from individuals with normozoospermia. METHODS: Normal sperm samples from 15 men aged 24 to 40 years were studied. Each sample was divided into six groups: fresh, freezing (frozen in liquid nitrogen), freeze-dried then preserved at room temperature for 1 month (FD-1m-RT), freeze-dried then preserved at room temperature for 2 months (FD-2m-RT), freeze-dried then preserved at 4 °C for 1 month (FD-1m-4 °C), and freeze-dried then preserved at 4 °C for 2 months (FD-2m-4 °C). The morphology, progressive motility, vitality, and DNA integrity of the sperm were evaluated in all groups. RESULTS: In all freeze-dried groups, sperm cells were immotile after rehydration. The freeze-dried groups also showed significantly less sperm vitality than the fresh and frozen groups. Significantly more morphological sperm abnormalities were found in the freeze-dried groups, but freeze-drying did not lead to a significantly higher DNA fragmentation index (DFI). The DFI was significantly higher in the FD-2m-RT group than in the other freeze-dried groups. CONCLUSION: The freeze-drying method preserved the integrity of sperm DNA. The temperature and duration of storage were also identified as factors that influenced the DFI. Accordingly, more research is needed on ways to improve sperm quality in the freeze-drying process.

Dermatofibrosarcoma protuberans challenges: a case series and review of the literature.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare variant of skin sarcoma which is characterized by proliferation of spindle cells in a storiform pattern. Although it is mostly benign in its primary stages, it can cause a high burden of morbidity unless it is thoroughly excised. CASE PRESENTATION: Here, we review six cases of DFSP which were characterized by skin lesions in various parts of the body. Patients were from 26 to 51 years old; four were Asian men and two were Asian women. Wide surgical excision was performed for all these patients and no extra treatment was considered. Samples were studied by hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) tests. Only one of our patients experienced recurrence after the initial surgery. CONCLUSION: Determining the best surgical method is still a dilemma in the treatment of DFSP lesions. There are numerous studies to prove the efficacy of various surgical interventions. Although DFSP is not commonly known as a malignant skin lesion, delay in treatment will have a catastrophic impact on patients' lives. Thus, applying an in-time surgical method (wide local excision in our cases) in treating DFSP is crucial in preventing recurrence as well as decreasing the morbidity burden of DFSP.

Splenogonadal fusion: A rare case report and literature review.

INTRODUCTION AND IMPORTANCE: Splenogonadal fusion is a rare congenital anomaly occurs when splenic tissue presents near or within a gonad. It mostly involves male children. Although it is benign and rare, making a pre-operation precise diagnosis is challenging which can lead to unnecessary invasive treatments. CASE PRESENTATION: A 3-year-old boy was presented by the chief complaint of a painless mass on the left testis and left inguinal hernia. He had a previous history of bilateral cryptorchidism and orchiopexy. Ultrasonography showed a small mass on the inferior pole of left testis and left reducible inguinal hernia. He went under left orchiectomy and hernia repair. Pathological investigation of the specimen resembled normal splenic tissue next to testicular tissue and the diagnosis of splenogonadal fusion was made. CLINICAL DISCUSSION: Splenogodal fusion cases can be challenging. Pain and sensation of mass in the scrotal sac are the most common presentation of splenogonadal fusion. Testicular malignancies can be considered as their main differential diagnosis, despite the fact that imaging and intra-operation frozen section can be helpful in making a definite diagnosis in some cases. It is mostly diagnosed incidentally during other procedures such as hernia repair or orchiopexy. Since it is benign, removal of tumor without orchiectomy is curative. CONCLUSION: In dealing with testicular mass in children, raising awareness of splenogonadal fusion have utmost importance to prevent unnecessary radical surgical interventions.