Probiotics with ameliorating effects on the severity of skin inflammation in psoriasis: Evidence from experimental and clinical studies

Experimental and clinical studies have confirmed safety and the medical benefits of probiotics as immunomodulatory medications. Recent advances have emphasized the critical effect of gastrointestinal bacteria in the pathology of inflammatory disorders, even, outside the gut. Probiotics have shown promising results for curing skin-influencing inflammatory disorders through modulating the immune response by manipulating the gut microbiome. Psoriasis is a complex inflammatory skin disease, which exhibits a microbiome distinct from the normal skin. In the present review, we considered the impact of gastrointestinal microbiota on the psoriasis pathogenesis, and through literature survey, attempted to explore probiotic species utilized for psoriasis treatment.     

Lentiviral Expression of Rabies Virus Glycoprotein in the Rat Hippocampus Strengthens Synaptic Plasticity

Rabies virus (RABV) is a neurotropic virus exclusively infecting neurons in the central nervous system. RABV encodes five proteins. Among them, the viral glycoprotein (RVG) plays a key role in viral entry into neurons and rabies pathogenesis. It was shown that the nature of the C-terminus of the RABV G protein, which possesses a PDZ-binding motif (PBM), modulates the virulence of the RABV strain. The neuronal protein partners recruited by this PBM may alter host cell function. This study was conducted to investigate the effect of RVG on synaptic function in the hippocampal dentate gyrus (DG) of rat. Two μl (10⁸ T.U./ml) of the lentiviral vector containing RVG gene was injected into the DG of rat hippocampus. After 2 weeks, the rat’s brain was cross-sectioned and RVG-expressing cells were detected by fluorescent microscopy. Hippocampal synaptic activity of the infected rats was then examined by recording the local field potentials from DG after stimulation of the perforant pathway. Short-term synaptic plasticity was also assessed by double pulse stimulation. Expression of RVG in DG increased long-term potentiation population spikes (LTP-PS), whereas no facilitation of LTP-PS was found in neurons expressing δRVG (deleted PBM). Furthermore, RVG and δRVG strengthened paired-pulse facilitation. Heterosynaptic long-term depression (LTD) in the DG was significantly blocked in RVG-expressing group compared to the control group. This blockade was dependent to PBM motif as rats expressing δRVG in the DG-expressed LTD comparable to the RVG group. Our data demonstrate that RVG expression facilitates both short- and long-term synaptic plasticity in the DG indicating that it may involve both pre- and postsynaptic mechanisms to alter synaptic function. Further studies are needed to elucidate the underlying mechanisms.

     

First report of c. 1499G>C mutation in a 6-month-child with cystic fibrosis

So far, more than 1800 mutations identified in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In this case report, we presented first report of c. 1499G>C mutation in a 6-month-old girl with cystic fibrosis (CF) diagnosis. A 6-month-old girl with weakness and meconium Ileus referred to the pediatric clinic in Ilam, in the west of Iran. Patient''s skin was dark and suffered from bronchiectasis. The sweat test was performed, and the concentration of chloride and sodium in patient''s sweat was 130-135 mmol/L and 125-128 mmol/L, respectively. The exon 10 mutation analysis of a CF patient was performed. CFTR mutation analysis revealed the identification of 2 mutations in patient, the mutations were p.F508del (ΔF508) and c. 1499G>C (cd500), respectively. The mutation c. 1499G>C (cd500) were found for the first time in the world. Assessing this mutation in future study and genetic investigation is recommended.     

A novel synthetic sRNA promoting protein overexpression in cell-free systems

Bacterial small RNAs (sRNAs) that regulate gene expression have been engineered for uses in synthetic biology and metabolic engineering. Here, we designed a novel non-Hfq-dependent sRNA scaffold that uses a modifiable 20 nucleotide antisense binding region to target mRNAs selectively and influence protein expression. The system was developed for regulation of a fluorescent reporter in vivo using Escherichia coli, but the system was found to be more responsive and produced statistically significant results when applied to protein synthesis using in vitro cell-free systems (CFS). Antisense binding sequences were designed to target not only translation initiation regions but various secondary structures in the reporter mRNA. Targeting a high-energy stem loop structure and the 3′ end of mRNA yielded protein expression knock-downs that approached 70%. Notably, targeting a low-energy stem structure near a potential RNase E binding site led to a statistically significant 65% increase in protein expression (p < 0.05). These results were not obtainable in vivo, and the underlying mechanism was translated from the reporter system to achieve better than 75% increase in recombinant diaphorase expression in a CFS. It is possible the designs developed here can be applied to improve/regulate expression of other proteins in a CFS.     

Cogrinding as a Tool to Produce Sustained Release Behavior for Theophylline Particles Containing Magnesium Stearate

The aim of the present study was to explore the cogrinding technique as a tool to slow down the drug release from capsule formulations. To this end, the physical mixtures of theophylline–magnesium stearate were prepared and subjected to different milling times (1, 15, 30, 120 min). In order to investigate the effect of magnesium stearate concentration on drug release, various concentrations of magnesium stearate (1%, 3%, 5%, and 10%, w/w) were used. The dissolution rate of the drug from coground samples and physical mixtures were determined at pH 6.5 according to USP. The results showed that all coground formulations showed slower release rates than their physical mixture counterparts. The effect of cogrinding time on the drug release was complex. Cogrinding time had no significant effect on drug release when the amount of magnesium stearate was 1% (w/w). When the amount of magnesium stearate was increased from 1% to 3% and cogrinding time increased from 1 to 5 min, there was a significant reduction in drug release. Beyond 5-min cogrinding, the drug release increased again. For coground samples containing 5% or 10% (w/w) magnesium stearate, generally, the highest drug release was obtained at higher cogrinding time. This was due to a significant increase in surface area of particles available for dissolution as proven by scanning electron microscopy results. Fourier transform infrared and differential scanning calorimetry results ruled out any significant interaction between theophylline and magnesium stearate in solid state.     

Delayed diagnosis of spinal cord schistosomiasis in a non-endemic country: A tertiary referral centre experience

BackgroundNeuroschistosomiasis is a severe complication of schistosomiasis, triggered by the local immune reaction to egg deposition, with spinal cord involvement the most well recognised form. Early treatment with praziquantel and high dose steroids leads to a reduction of neurological sequelae. The rarity of this condition in returning travellers to high income countries can result in delayed diagnosis and treatment. We aimed to evaluate the diagnosis and management of neuroschistosomiasis in a UK national referral centre.Materials/MethodsA retrospective review of confirmed clinical cases of spinal schistosomiasis referred to the Hospital for Tropical Diseases, UK, between January 2016 and January 2020 was undertaken. Electronic referral records were interrogated and patient demographic, clinical, laboratory, and radiological data collected.ResultsFour cases of neuroschistosomiasis were identified. The median age at diagnosis was 28 (range 21 to 50) with three male patients. All patients had epidemiological risk factors for schistosomiasis based on travel history and freshwater exposure; two in Uganda (River Nile), one in Malawi and one in Nigeria. All patients presented with features of transverse myelitis including back pain, leg weakness, paraesthesia and urinary dysfunction. The mean time from presentation to health services to definitive treatment was 42.5 days (range 16–74 days). Diagnosis was confirmed with CSF serology for schistosomiasis in all cases. Radiological features on MRI spine included enhancement focused predominantly in the lower thoracic spinal cord in three cases and the conus in one patient. All patients received a minimum of three days of oral praziquantel and high dose steroids. At three-month follow-up, one patient had complete resolution of symptoms and three had residual deficit; one patient was left with urinary and faecal incontinence, another had urinary retention, and the final patient has persistent leg pains and constipation.ConclusionWe observed a marked delay in diagnosis of neuroschistosomiasis in a non-endemic country. We advocate undertaking a thorough travel history, early use of imaging and CSF schistosomal serology to ensure early diagnosis of neuroschistosomiasis in patients presenting with consistent symptoms. If schistosomal diagnostics are not immediately available, presumptive treatment under the guidance of a tropical medicine specialist should be considered to minimize the risk of residual disability. We advocate for consensus guidelines to be produced and reporting to be performed in a uniform way for patients with spinal schistosomiasis.     

Contribution of atherosclerotic plaque location and severity to the near-wall hemodynamics of the carotid bifurcation: an experimental study and FSI modeling

Biomechanics and Modeling in Mechanobiology - Atherosclerosis is initiated by endothelial injury that is related to abnormal values of hemodynamic parameters such as wall shear stress (WSS),...     

Three-dimensional cell culture (3DCC) improves secretion of signaling molecules of mesenchymal stem cells (MSCs)

Biotechnology Letters - The secretome of mesenchymal stem cells (MSCs), also called MSC-conditioned media (MSC-CM), represents one of the promising strategies for cellular therapy and tissue repair...