Development and evaluation of methotrexate-loaded nanoemulsion formulation for topical treatment of psoriasis.

Psoriasis is a chronic inflammatory disease that is becoming widespread and is associated with many kinds of additional severe diseases. The present study aimed to develop a methotrexate-loaded almond oil-based nanoemulsion formulation (MTX NE) for topical administration. The drug-loaded nanoemulsion formulation was prepared by high shear homogenization technique.

A pH-responsive bi-MIL-88B MOF coated with folic acid-conjugated chitosan as a promising nanocarrier for targeted drug delivery of 5-Fluorouracil.

Cancer has remained one of the leading causes of death worldwide, with a lack of effective treatment. The intrinsic shortcomings of conventional therapeutics regarding tumor specificity and non-specific toxicity prompt us to look for alternative therapeutics to mitigate these limitations. In this regard, we developed multifunctional bimetallic (FeCo) bi-MIL-88B-FC MOFs modified with folic acid-conjugated chitosan (FC) as drug delivery systems (DDS) for targeted delivery of 5-Fluorouracil (5-FU).

Collaterally Sensitive β-Lactam Drugs as an Effective Therapy against the Pre-Existing Methicillin Resistant (MRSA) Biofilms.

Methicillin-resistant (MRSA) is among the leading causes of nosocomial infections and forms biofilms, which are difficult to eradicate because of their increasing resistance to antimicrobial agents. This is especially true for pre-existing biofilms. The current study focused on evaluating the efficacy of three β-lactam drugs, meropenem, piperacillin, and tazobactam, alone and in combination against the MRSA biofilms.

Partnership 4.0: smallholder farmer partnership solutions.

The current pseudo-partnership pattern causes the farmers' income to be low from the results of their farming activities, so a partnership pattern is needed that is able to create a mutual partnership. The research which was conducted in Cikarawang Village, Bogor Regency, West Java Province - Indonesia aims; (1) recognize the existing condition of farmers and the use of agricultural land; (2) knowing the distribution of agricultural commodities; (3) identify existing partnership patterns; and (4) provide solutions for partnership patterns that benefit farmers. By using mixed-methods combined with the Drone Participatory Mapping (DPM) approach to produce (DDP), this study succeeded in identifying three statuses of farmers, namely: cultivators, owners and cultivators of their own land, and owners who work on their own land at the same time working on other people's land, with an average access to land management of 3,437.

Define the Two Molecular Subtypes of Epithelioid Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a fatal disease of respiratory system. Despite the availability of invasive biomarkers with promising results, there are still significant diagnostic and therapeutic challenges in the treatment of MPM. One of three main mesothelioma cell types, epithelioid mesothelioma makes up approximately 70% of all mesothelioma cases.

Programmable Drug Release from a Dual-Stimuli Responsive Magnetic Metal-Organic Framework.

Along with the increasing incidence of cancer and drawbacks of traditional drug delivery systems (DDSs), developing novel nanocarriers for sustained targeted-drug release has become urgent. In this regard, metal-organic frameworks (MOFs) have emerged as potential candidates due to their structural flexibility, defined porosity, lower toxicity, and biodegradability. Herein, a FeMn-based ferromagnetic MOF was synthesized from a preassembled FeMn(μ-O) cluster.

Microwave-Assisted Physically Cross-Linked Chitosan-Sodium Alginate Hydrogel Membrane Doped with Curcumin as a Novel Wound Healing Platform.

This project purposes to develop chitosan and sodium alginate-based hydrogel membranes loaded with curcumin through microwave-based physical cross-linking technique and its evaluation for wound healing potential. For the purpose, curcumin-loaded chitosan and sodium alginate membranes were developed using microwave at fixed frequency of 2450 MHz, power 350 W for 60 s, and tested for their physicochemical attributes like swelling, erosion, surface morphology, drug content, and in vitro drug release. The membranes were also subjected to tensile strength and vibrational and thermal analysis followed by testing in vivo on animals.

A Participatory Investigation of Bovine Health and Production Issues in Pakistan.

Systems to record the frequency of animal health events in Pakistan are limited. A participatory approach was used to address gaps in farmers' knowledge and understanding of bovine health and production issues in five agroecological zones (AEZs) of Pakistan. Participatory tools, including simple ranking, pairwise ranking, constraint impact scoring, and constraint profiling were used in group discussions with farmers and animal health professionals (AHPs) in six districts of two provinces, Punjab and Sindh.

Molecular docking, anti-proliferative activity and induction of apoptosis in human liver cancer cells treated with androstane derivatives: Implication of PI3K/AKT/mTOR pathway.

Worldwide, cancer is still an area with high unmet medical need. Lead optimization efforts towards structure-based drug design were employed to discover newly synthesized hetero-steroid derivatives with promising anticancer effects against hepatocellular carcinoma (HCC). The aim of our study is to evaluate the anti-proliferative activity and the mechanism, a dual PI3K/mTOR inhibitor, and mechanism of action of a series of heterocylic androstane derivatives as anti-HCC agent.

Exome sequence analysis in consanguineous Pakistani families inheriting Bardet-Biedle syndrome determined founder effect of mutation c.299delC (p.Ser100Leufs*24) in BBS9 gene.

Background: Bardet-Biedl syndrome (BBS) is characterized by a heterogeneous phenotypic spectrum of retinopathy, intellectual disability (ID), obesity, polydactyly, and kidney dysfunctions as the major clinical features. Genetic investigations have reported 21 BBS genes, the products of which are mostly located at the centrosome, basal body or the ciliary transition zone.

Methods: In the present genetic report, we analyzed two apparently unrelated consanguineous BBS families from Dera Ismail Khan (D.

Detection of rifampicin resistance of Mycobacterium tuberculosis using multiplex allele specific polymerase chain reaction (MAS-PCR) in Pakistan.

Drug resistance in tuberculosis (TB) is a major public health challenge in developing countries such as Pakistan. Multiplex allele specific polymerase chain reaction (MAS-PCR) is a DNA amplification method that could contribute to rapid detection and control of drug resistant tuberculosis (DR-TB) in Pakistan. The purpose of this study was to test the utility of MAS-PCR to detect resistance in Pakistan.

Molecular genetic analysis of consanguineous families with primary microcephaly identified pathogenic variants in the ASPM gene.

Autosomal recessive primary microcephaly is a rare genetic disorder that is characterized by reduced head circumference and a varying degree of intellectual disability. Genetic studies on consanguineous families with primary microcephaly have identified 15 (MCPH) causative genes that include MCPH1, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1, CDK6, CENPE, SASS6 MFSD2A ANKLE2 and CIT (Khan et al. 2014; Yamamoto et al.

Ophthalmo-genetic analysis of Pakistani patients with nonsyndromic oculocutaneous albinism through whole exome sequencing.

Oculocutaneous albinism (OCA) is a disorder of defective melanin biosynthesis that is characterized by hypo-pigmentation of skin, hair and retinal pigment epithelium. Phenotypically, OCA patients exhibit white milky skin, whitish to golden hair and deterioration of retinal cells. Until recently, genetic studies have reported seven causative genes (TYR, TYRP1, OCA2, SLC45A2, SLC24A2, C10ORF11 and MCIR) and an uncharacterized OCA5 locus.

The Molecular Genetics of Autosomal Recessive Nonsyndromic Intellectual Disability: a Mutational Continuum and Future Recommendations.

Intellectual disability (ID) is a clinical manifestation of the central nervous system without any major dysmorphologies of the brain. Biologically it affects learning capabilities, memory, and cognitive functioning. The basic defining features of ID are characterized by IQ<70, age of onset before 18 years, and impairment of at least two of the adaptive skills.

Proliferation status defines functional properties of endothelial cells.

Homeostasis of solid tissue is characterized by a low proliferative activity of differentiated cells while special conditions like tissue damage induce regeneration and proliferation. For some cell types it has been shown that various tissue-specific functions are missing in the proliferating state, raising the possibility that their proliferation is not compatible with a fully differentiated state. While endothelial cells are important players in regenerating tissue as well as in the vascularization of tumors, the impact of proliferation on their features remains elusive.

Highly biocompatible behaviour and slow degradation of a LDH (layered double hydroxide)-coating on implants in the middle ear of rabbits.

Chronic inflammation can irreversibly damage components of the ossicular chain which may lead to sound conduction deafness. The replacement of impaired ossicles with prostheses does not reduce the risk of bacterial infections which may lead to loss of function of the implant and consequently to additional damage of the connected structures such as inner ear, meninges and brain. Therefore, implants that could do both, reconstruct the sound conduction and in addition provide antibacterial protection are of high interest for ear surgery.

Controlled drug release from antibiotic-loaded layered double hydroxide coatings on porous titanium implants in a mouse model.

As an alternative to degradable organic coatings the possibility of using layered double hydroxides (LDHs) to generate implant coatings for controlled drug delivery was evaluated in vivo and in vitro. Coatings prepared from LDH suspensions dissolved slowly and appeared compatible with cultured cells. LDH coatings loaded with an antibiotic resulted in antibacterial effects in vitro.

De novo hem- and lymphangiogenesis by endothelial progenitor and mesenchymal stem cells in immunocompetent mice.

Cellular pro-angiogenic therapies may be applicable for the treatment of peripheral vascular diseases. Interactions between mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) may provide such a treatment option. With the exception of some studies in man, experiments have only been performed in immunodeficient mice and rats.

Assessment of cellular reactions to magnesium as implant material in comparison to titanium and to glyconate using the mouse tail model.

Purpose: Nowadays, research in magnesium alloys as a biodegradable implant material has increased. The aim of this study was to examine osteoinductive properties and tissue responses to pure magnesium in comparison to conventional permanent (titanium) and to degradable (glyconate) implant materials.

Methods: Magnesium wires (0.

The formation of an organic coat and the release of corrosion microparticles from metallic magnesium implants.

Magnesium alloys have been proposed as prospective degradable implant materials. To elucidate the complex interactions between the corroding implants and the tissue, magnesium implants were analyzed in a mouse model and the response was compared to that induced by Ti and by the resorbable polymer polyglactin, respectively. One month after implantation, distinct traces of corrosion were apparent but the magnesium implants were still intact, whereas resorbable polymeric wound suture implants were already fragmented.

Layered double hydroxides as efficient drug delivery system of ciprofloxacin in the middle ear: an animal study in rabbits.

Chronic otitis media is a common disease often accompanied by recurrent bacterial infections. These may lead to the destruction of the middle ear bones such that prostheses have to be implanted to restore sound transmission. Surface coatings with layered double hydroxides (LDHs) are evaluated here as a possibility for drug delivery systems with convenient advantages such as low cytotoxicity and easy synthesis.

Evaluation of single-cell force spectroscopy and fluorescence microscopy to determine cell interactions with femtosecond-laser microstructured titanium surfaces.

One goal in biomaterials research is to limit the formation of connective tissue around the implant. Antiwetting surfaces are known to reduce ability of cells to adhere. Such surfaces can be achieved by special surface structures (lotus effect).

Comparison of in vitro and in vivo protein release from hydrogel systems.

Hydrogel systems based on hydroxyethyl starch-polyethylene glycol methacrylate (HES-P(EG)(6)MA) or hydroxyethyl starch methacrylate (HES-MA) were used to assess the protein release behavior. Here, we analyzed the in vitro release of FITC-anti-human antibodies incorporated in either HES-P(EG)(6)MA or HES-MA hydrogel delivery systems in PBS or human serum. In addition, hydrogel disks and microparticles prepared from the two polymers were subcutaneously implanted in BALB/c mice.