Saikosaponin-d,a novel SERCA inhibitor,induces autophagic cell death in apoptosis-defective cells

Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase pump, leading to autophagy induction through the activation of the Ca²⁺/calmodulin-dependent kinase kinase–AMP-activated protein kinase–mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells.     

Distribution of Streptomycin Resistant Strains of Erwinia amylovora in Egypt during 1988

A survey of the occurrence of strains of Erwinia amylovora resistant to streptomycin in certain Egyptian pear orchards was earned out during April and May 1988. Twenty-two isolates out of 604 isolates collected from 11 orchards showed resistance to streptomycin. All the streptomycin resistant (Str^r) strains isolated in the present work were resistant to high levels of streptomycin with minimal inhibitory concentrations ranging from 1000 to 3000 μg/ml. The occurrence of Str^r strains in Egypt is still limited and the population of resistant strains was at relatively low level. However, such occurrence of E. amylovora with resistance to streptomycin is a potentially serious situation.     

Effect of RA233 on Platelet Function In Vitro

RA233, a new pyrimido-pyrimidine compound, is a powerful inhibitor of platelet function tested in vitro; it inhibits calcium and adenosine diphosphate (A.D.P.)-induced platelet aggregation, inhibits the retention of platelets by glass beads, decreases the release of platelet factor 3 by kaolin, and inhibits clot retraction. In some in-vitro systems RA233 is significantly more potent that its analogue RA433 in inhibiting platelet function.     

Clinical signs and household characteristics associated with human fascioliasis among rural population in Egypt: a case-control study

The symptomatology associated with human fascioliasis has been studied mostly in hospitalised subjects. Very little is known about clinical signs and symptoms associated with infections in human endemic zones, as well as on possible new ways of transmission which might be responsible for the increased number of human cases reported in recent years. This information is of great importance to facilitate diagnosis and plan effective control measures. With the objective to identify clinical signs, blood tests, household characteristics and hygienic habits associated with human fascioliasis, a cross-sectional case-control study was implemented among the rural population of three endemic foci in the Nile Delta, Egypt. Clinical history was collected from 53 cases of fascioliasis and the same number of individually matched controls. They received a complete clinical examination and a range of blood tests was performed on them. Information on socio-economic conditions, dietary and hygienic habits was also collected. The most important complaints, associated with the infection, were right abdominal pain (Odds Ratio 20, P = 0.005), epigastric burning (o.r. 16, P = 0.007) and nausea (o.r. 8, P = 0.05). Blood analyses reported a marked increase in blood eosinophils (o.r 1.3, P = 0.001) among cases. The presence of cows (o.r 3.2), buffaloes (o.r 3.0) and goats (o.r 2.6) in the household was closely associated with the infection together with the habit to bring those animals to the canal for bathing and/or drinking (o.r. 3.2). Among dietary habits investigated, eating raw seeds was more common in cases than controls (o.r. 9, P = 0.03) and emerged as a possible new way of infection.     

An extensive review on antifungal approaches in the treatment of mucormycosis

During the period of COVID-19, the occurrences of mucormycosis in immunocompromised patients have increased significantly. Mucormycosis (black fungus) is a rare and rapidly progressing fungal infection associated with high mortality and morbidity in India as well as globally. The causative agents for this infection are collectively called mucoromycetes which are the members of the order Mucorales. The diagnosis of the infection needs to be performed as soon as the occurrence of clinical symptoms which differs with types of Mucorales infection. Imaging techniques magnetic resonance imaging or computed tomography scan, culture testing, and microscopy are the approaches for the diagnosis. After the diagnosis of the infection is confirmed, rapid action is needed for the treatment in the form of antifungal therapy or surgery depending upon the severity of the infection. Delaying in treatment declines the chances of survival. In antifungal therapy, there are two approaches first-line therapy (monotherapy) and combination therapy. Amphotericin B ( 1 ) and isavuconazole ( 2 ) are the drugs of choice for first-line therapy in the treatment of mucormycosis. Salvage therapy with posaconazole ( 3 ) and deferasirox ( 4 ) is another approach for patients who are not responsible for any other therapy. Adjunctive therapy is also used in the treatment of mucormycosis along with first-line therapy, which involves hyperbaric oxygen and cytokine therapy. There are some drugs like VT-1161 ( 5 ) and APX001A ( 6 ), Colistin, SCH 42427, and PC1244 that are under clinical trials. Despite all these approaches, none can be 100% successful in giving results. Therefore, new medications with favorable or little side effects are required for the treatment of mucormycosis.     

Ultrasound system to measure esophageal varix pressure: an in vitro validation study

We report our experience with an ultrasound system to measure esophageal varix pressure in an in vitro model. The ultrasound system consists of a 12.5 MHz frequency intraluminal ultrasound probe, a water infusion catheter, and a manometry catheter, all contained within a nondistensible latex bag. Esophagi and external jugular veins were harvested from five pigs. The vein and ultrasound system were placed inside the esophagus. One end of the vein was connected to a water reservoir to modulate its pressure; the other end was connected in two different ways to simulate hydrodynamic and hydrostatic flow conditions. The bag was inflated with water until vein occlusion was discernible on the ultrasound images. The influences of vein pressure, vein cross-sectional area and esophageal elasticity on the ultrasound measurement of vein pressure were assessed. A total of 108 trials were performed at nine different vein pressures. Complete vein occlusion occurred when the bag pressure was slightly greater (1.4 +/- 0.7 mmHg) than the vein pressure. For a vein pressure of 25 mmHg, the average occlusion and opening pressures were 27 +/- 0.2 and 25.7 +/- 0.3 mmHg, respectively (P < .05) suggesting that the vein opening pressure on the ultrasound images is more accurate than the vein closing pressure. In conclusion, the ultrasound technique can accurately measure intravariceal pressure in vitro. The bag pressure at the point of vein reopening is the best determinant of the vein pressure.     

Polymorphisms of TNFalpha, IL1beta, and IL1RN genes in chronic obstructive pulmonary disease

It is recognized that genetic factors play a role in the susceptibility to COPD. COPD is characterized by airflow limitation. Chronic inflammation causes small airway disease and parenchymal destruction, leading to the airflow limitation. Polymorphisms in pro-inflammatory cytokine genes may confer a risk for the development of COPD. A case-control association study was performed in Japanese population (88 COPD patients and 61 controls) and Egyptian population (106 patients and 72 controls). Genotype and allele frequencies of the TNFalpha -308 G/A and +489 G/A polymorphisms, the IL1beta -511 C/T, -31 T/C, and +3954 C/T polymorphisms, and a VNTR polymorphism in intron 2 of the IL1RN gene were investigated. In addition, pairwise haplotype frequencies were analyzed. When studied independently, none of the polymorphisms were associated with the development of COPD in both populations. However, in the Egyptian population, the distributions of the haplotype (IL1beta -31 T/C : IL1beta +3954 C/T) were significantly different between the COPD patients and the controls (p(corr)=0.0037). Our findings suggest that this haplotype within the IL1beta gene may be involved in the pathogenesis of COPD and that the genetic factors of COPD susceptibility might be different between different populations.