Potential Impact of SOD2 (rs4880; p.Val16Ala) Variant with the Susceptibility for Childhood Bronchial Asthma.

Oxidative stress is a sophisticated situation that orignates from the accumulation of reactive free radicals within cellular compartments. The antioxidant mechanism of the MnSOD enzyme facilitates the removal of these lethal oxygen species from cellular components. The main goal of this pertained work is to study the contribution of the SOD2 (rs4880; p.Val16Ala) variant to the development of bronchial asthma among children. The study's design was carried out based on a total of 254 participants including 127 asthmatic children (91 atopic and 36 non-atopic) along with 127 unrelated healthy controls. Allelic discrimination analysis was executed using the T-ARMS-PCR protocol. This potential variant conferred a significant association with decreased risk of bronchial asthmatic children under allelic (OR = 0.56, P-value = 0.002), recessive (OR = 0.32, P-value = 0.011), and dominant (OR = 0.51, P-value = 0.040) models. Additionally, atopic and non-atopic asthmatic children indicated a protection against bronchial asthma development under allelic, and dominant models (p-value < 0.05). Our findings suggested that the SOD2*rs4880 variant was correlated with decreased risk of childhood bronchial asthma.

Effectiveness of intralesional vitamin D3 injection in the treatment of common warts: Single-blinded placebo-controlled study.

Warts are common viral infection of the skin, usually treated with destructive methods like electrocautery, cryotherapy or laser ablation. Topical vitamin D has been used to treat warts with variable success is to evaluate the efficacy of intralesional vitamin D3 injection in the treatment of common warts. Fifty patients were divided into two groups: 30 patients as cases group who received intralesional injection of 0.2 mL of vitamin D3 (300,000 IU) into the base of mother wart for two sessions and another 20 patients as a control group who were injected with normal saline solution. Standardized photographs were taken before the procedure, and 1 month and 3 months after the procedure. The degree of the response was classified into complete, partial, and no response. Complete clearance of the target injected warts occurred in 40% of patients in cases group while it occurred only in 5% of patients in control group (p ≤ .001) that was statistically significant. Intralesional injection of vitamin D3 may be considered a good and safe modality for the treatment of common warts.

High versus low-dose caffeine for apnea of prematurity: a randomized controlled trial.

UNLABELLED: The optimum caffeine dose in preterm infants has not been well investigated. We aimed to compare the efficacy and safety of high versus low-dose caffeine citrate on apnea of prematurity (AOP) and successful extubation of preterm infants from mechanical ventilation. We compared high-dose (loading 40 mg/kg/day and maintenance of 20 mg/kg/day) versus low-dose (loading 20 mg/kg/day and maintenance of 10 mg/kg/day) caffeine citrate in preterm infants <32 weeks gestation, presented with AOP within the first 10 days of life. A total of 120 neonates (60 in each group) were enrolled. High-dose caffeine was associated with a significant reduction in extubation failure in mechanically ventilated preterm infants (p<0.05), the frequency of apnea (p<0.001), and days of documented apnea (p<0.001). High-dose caffeine was associated with significant increase in episodes of tachycardia (p<0.05) without a significant impact on physician decision to withhold caffeine. CONCLUSION: The use of higher, than current standard, dose of caffeine may decrease the chance of extubation failure in mechanically ventilated preterm infants and frequency of AOP without significant side effects. WHAT IS KNOWN: • Caffeine therapy for treatment of apnea of prematurity has been well established over the past few years. The optimal loading and maintenance dose of caffeine in preterm infants is not well-studied. What is New: • This double blind randomized controlled trial demonstrated that using a higher, than current standard, loading and maintenance doses of caffeine for treatment of apnea in preterm infants is well tolerated and significantly decrease the frequency of apnea.

Multifunctional liposomal nanostructure-mediated siRNA/bortezomib co-delivery for SHARP1 knockdown in MLL-AF6 acute myeloid leukemia.

Acute myeloid leukemia (AML) has an extremely poor prognosis and high relapse and fatality rates. New therapeutic mechanisms for molecular targeted delivery are urgently needed to improve patient survival. In this study, we targeted the oncogenic transcription factor SHARP1 using multifunctional small interfering RNA (siRNA) and bortezomib (BTZ)-loaded cRGD-guided PEGylated cationic liposomal nanostructures to monitor their antileukemic activity in MLL-AF6 AML cells. Efficient siRNA/BTZ co-delivery by the nanostructures inhibited cell viability and the clonogenic growth as well as stimulated apoptosis of AML cells. We hypothesized that SHARP1 downregulation induced the accumulation of non-functional MLL-AF6, DOT1L, MEN1, and LEDGF fusion proteins, preventing MLL-AF complex formation and downregulating RAS-GTP and Bcl-2 expression, consequently triggering autophagy and apoptosis. The BTZ combination substantially augmented therapeutic synergy and enhanced autophagic and apoptotic events. Our findings demonstrate a state-of-the-art biodegradable nanoplatform for siRNA/BTZ co-delivery with targeted SHARP1 knockdown, demonstrating a potential therapeutic option for MLL-AF6 AML.

Bioengineered PLEKHA7 nanodelivery regularly induces behavior alteration and growth retardation of acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most lethal leukemia with an extremely poor prognosis and high relapse rates. In leukemogenesis, adhesion abnormalities can readily guide an imbalance between hematopoietic progenitor cells and bone marrow stromal cells, altering the normal hematopoietic bone marrow microenvironment into leukemic transformation that enhances leukemic proliferation. Here, we have firstly studied the PLEKHA7 expression in leukemic cells to assess their growth capability affected by the restoration of PLEKHA7 in the cells. The efficacy of PLEKHA7-loaded cRGD-mediated PEGylated cationic lipid nanoparticles for efficient PLEKHA7 delivery in leukemic cells as well as the effect of PLEKHA7 on the regulated induction of AML behavior and growth alterations were investigated. PLEKHA7 re-expression diminished colony-forming ability and reinforced the incidence of growth retardation without apoptosis in AML cell lines. PLEKHA7 regulated the restoration of cell surface adhesion and integrity during normal homeostasis. Our findings revealed that PLEKHA7 functions as a behavior and growth modulator in AML. To our knowledge, the role of PLEKHA7 in AML had not been studied previously and our data could be exploited for further mechanistic studies and insights into altering human AML behavior and growth.

Anterior Segment Optical Coherence Tomography (AS-OCT) Guided Reversal of Edematous Punctal Occlusion.

AIM: To evaluate the role of anterior segment-optical coherence tomography (AS-OCT) in the diagnosis of punctal stenosis and to compare punctal parameters before and after medical treatment. PATIENTS AND METHODS: The study was conducted on 40 eyes of 24 patients who had acquired inflammatory punctal stenosis and had persistent epiphora (persistent epiphora group - PEG), and 20 eyes of 10 subjects with normal punctal openings as a control group (control group - CG). We measured the outer punctal diameter (OPD), recorded the visibility of the internal punctum and punctal depth (PD) using AS-OCT, before and 1 month after treatment with preservative free methylprednisolone 5% eye drops. Punctal diameter, tear meniscus height (TMH) and Munk's score were compared to the control group before and after treatment. RESULTS: The mean OPD of the PEG before treatment (455.5 ± 174 µm) was significantly smaller than that of the CG (590.9 ± 106.6 µm) (P= 0.002). The mean OPD of the PEG significantly increased to 484.6 ± 175.5 µm after treatment (P <0.001). Also, the visibility of vertical canaliculus lumen and PD were restored in 70% of eyes. The TMH was much higher in the PEG than in the CG before treatment (P<0.05). However, after treatment the difference was not statistically significant. CONCLUSION: AS-OCT parameters were useful in monitoring and measuring the efficacy of medical treatment in relieving punctal edema, which subsequently resulted in reducing the epiphora symptoms.

Aegicetus gehennae, a new late Eocene protocetid (Cetacea, Archaeoceti) from Wadi Al Hitan, Egypt, and the transition to tail-powered swimming in whales.

Aegicetus gehennae is a new African protocetid whale based on a partial skull with much of an associated postcranial skeleton. The type specimen, Egyptian Geological Museum, Cairo [CGM] 60584, was found near the base of the early-Priabonian-age (earliest late Eocene) Gehannam Formation of the Wadi Al Hitan World Heritage Site in Egypt. The cranium is distinctive in having ventrally-deflected exoccipitals. The vertebral column is complete from cervical C1 through caudal Ca9, with a vertebral formula of 7:15:4:4:9+, representing, respectively, the number of cervical, thoracic, lumbar, sacral, and caudal vertebrae. CGM 60584 has two more rib-bearing thoracic vertebrae than other known protocetids, and two fewer lumbars. Sacral centra are unfused, and there is no defined auricular surface on the ilium. Thus there was no weight-bearing sacroiliac joint. The sternum is distinctive in being exceptionally broad and flat. The body weight of CGM 60584, a putative male, is estimated to have been about 890 kg in life. Long bones of the fore and hind limbs are shorter than expected for a protocetid of this size. Bones of the manus are similar in length and more robust compared to those of the pes. A log vertebral length profile for CGM 60584 parallels that of middle Eocene Maiacetus inuus through the anterior and middle thorax, but more posterior vertebrae are proportionally longer. Vertebral elongation, loss of a sacroiliac articulation, and hind limb reduction indicate that Aegicetus gehennae was more fully aquatic and less specialized as a foot-powered swimmer than earlier protocetids. It is doubtful that A. gehennae had a tail fluke, and the caudal flattening known for basilosaurids is shorter relative to vertebral column length than flattening associated with a fluke in any modern whale. Late protocetids and basilosaurids had relatively long skeletons, longer than those known earlier and later, and the middle-to-late Eocene transition from foot-powered to tail-powered swimming seemingly involved some form of mid-body-and-tail undulation.

Stomach contents of the archaeocete Basilosaurus isis: Apex predator in oceans of the late Eocene.

Apex predators live at the top of an ecological pyramid, preying on animals in the pyramid below and normally immune from predation themselves. Apex predators are often, but not always, the largest animals of their kind. The living killer whale Orcinus orca is an apex predator in modern world oceans. Here we focus on an earlier apex predator, the late Eocene archaeocete Basilosaurus isis from Wadi Al Hitan in Egypt, and show from stomach contents that it fed on smaller whales (juvenile Dorudon atrox) and large fishes (Pycnodus mokattamensis). Our observations, the first direct evidence of diet in Basilosaurus isis, confirm a predator-prey relationship of the two most frequently found fossil whales in Wadi Al-Hitan, B. isis and D. atrox. This extends our understanding of their paleoecology. Late Eocene Basilosaurus isis, late Miocene Livyatan melvillei, and modern Orcinus orca are three marine apex predators known from relatively short intervals of time. Little is known about whales as apex predators through much of the Cenozoic era, and whales as apex predators deserve more attention than they have received.

Antitumor activity of intratracheal inhalation of temozolomide (TMZ) loaded into gold nanoparticles and/or liposomes against urethane-induced lung cancer in BALB/c mice.

The current study aimed to develop gold nanoparticles (GNPs) and liposome-embedded gold nanoparticles (LGNPs) as drug carriers for temozolomide (TMZ) and investigate the possible therapeutic effects of intratracheal inhalation of nanoformulation of TMZ-loaded gold nanoparticles (TGNPs) and liposome-embedded TGNPs (LTGNPs) against urethane-induced lung cancer in BALB/c mice. Physicochemical characters and zeta potential studies for gold nanoparticles (GNPs) and liposome-embedded gold nanoparticles (LGNPs) were performed. The current study was conducted by inducing lung cancer chemically via repeated exposure to urethane in BALB/C mice. GNPs and LGNPs were exhibited in uniform spherical shape with adequate dispersion stability. GNPs and LGNPs showed no significant changes in comparison to control group with high safety profile, while TGNPs and LTGNPs succeed to improve all biochemical data and histological patterns. GNPs and LGNPs are promising drug carriers and succeeded in the delivery of small and efficient dose of temozolomide in treatment lung cancer. Antitumor activity was pronounced in animal-treated LTGNPs, these effects may be due to synergistic effects resulted from combination of temozolomide and gold nanoparticles and liposomes that may improve the drug distribution and penetration.