MiR-146b-5p enriched bioinspired exosomes derived from fucoidan-directed induction mesenchymal stem cells protect chondrocytes in osteoarthritis by targeting TRAF6.

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation and inflammation. In recent years, mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) have attracted widespread attention for their potential role in modulating OA pathology. However, the unpredictable therapeutic effects of exosomes have been a significant barrier to their extensive clinical application. In this study, we investigated whether fucoidan-pretreated MSC-derived exosomes (F-MSCs-Exo) could better protect chondrocytes in osteoarthritic joints and elucidate its underlying mechanisms. In order to evaluate the role of F-MSCs-Exo in osteoarthritis, both in vitro and in vivo studies were conducted. MiRNA sequencing was employed to analyze MSCs-Exo and F-MSCs-Exo, enabling the identification of differentially expressed genes and the exploration of the underlying mechanisms behind the protective effects of F-MSCs-Exo in osteoarthritis. Compared to MSCs-Exo, F-MSCs-Exo demonstrated superior effectiveness in inhibiting inflammatory responses and extracellular matrix degradation in rat chondrocytes. Moreover, F-MSCs-Exo exhibited enhanced activation of autophagy in chondrocytes. MiRNA sequencing of both MSCs-Exo and F-MSCs-Exo revealed that miR-146b-5p emerged as a promising candidate mediator for the chondroprotective function of F-MSCs-Exo, with TRAF6 identified as its downstream target. In conclusion, our research results demonstrate that miR-146b-5p encapsulated in F-MSCs-Exo effectively inhibits TRAF6 activation, thereby suppressing inflammatory responses and extracellular matrix degradation, while promoting chondrocyte autophagy for the protection of osteoarthritic cartilage cells. Consequently, the development of a therapeutic approach combining fucoidan with MSC-derived exosomes provides a promising strategy for the clinical treatment of osteoarthritis.

Phenylacetyl-/Trolox- Amides: Synthesis, Sigma-1, HDAC-6, and Antioxidant Activities.

In search of novel multi-mechanistic approaches for treating Alzheimer's disease (AD), we have embarked on synthesizing single small molecules for probing contributory roles of the following combined disease targets: sigma-1 (σ-1), class IIb histone deacetylase-6 (HDAC-6), and oxidative stress (OS). Herein, we report the synthesis and partial evaluation of 20 amides (i.e., phenylacetic and Trolox or 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid derivatives). Target compounds were conveniently synthesized via amidation by either directly reacting acyl chlorides with amines or condensing acids with amines in the presence of coupling agents 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo [4,5-b] pyridinium 3-oxide hexafluorophosphate (HATU) or 1,1'-carbonyldiimidazole (CDI). Overall, this project afforded compound 8 as a promising lead with σ-1 affinity (Ki = 2.1 µM), HDAC-6 (IC50 = 17 nM), and antioxidant (1.92 Trolox antioxidant equivalents or TEs) activities for optimization in ensuing structure-activity relationship (SAR) studies.

Critical Evaluation of Different Lysosomal Labeling Methods Used to Analyze RNA Nanocarrier Trafficking in Cells.

The use of nucleic acids to regulate gene expression is a rapidly developing field with immense clinical potential. Nanomaterials are frequently used to deliver nucleic acids into cells as they can overcome the poor cellular uptake and endo/lysosomal degradation of bare nucleic acids. For these nanocarriers to be effective, they must escape endo/lysosomal compartments to deliver their nucleic acid cargo into the cytosol (for ribonucleic acid (RNA)) or nucleus (for deoxyribonucleic acid (DNA)). This process is poorly understood and remains an area of active research toward the goal of developing effective delivery strategies. Fluorescent endo/lysosomal markers are among the most widely employed tools used to evaluate the endosomal escape of nucleic acid nanocarriers. However, the endo/lysosomal labeling method may alter the extent of and route of nanocarrier uptake by cells. The impact of these markers on cellular function and cell-nanocarrier interactions has not been probed in a systematic manner. To investigate this, we compared the effects of several common lysosomal labeling methods, namely, LysoTracker Red (LT Red), transient lysosomal-associated membrane protein 1-mutant green fluorescent protein (LAMP1-mGFP) transfection (Transient GFP), and stable lentiviral LAMP1-mGFP transfection (Stable GFP), on cellular metabolic activity, nanocarrier uptake, nanocarrier/lysosomal label colocalization, and gene silencing potency in U87 glioblastoma and MDA-MB-231 breast cancer cells using polyethyleneimine (PEI)/ribonucleic acid (RNA) polyplexes as a model nanocarrier. In both U87s and MDA-MB-231s, Transient GFP and LT Red labeling reduced metabolic activity relative to untransfected (Parental) cells, while Stable GFP labeling increased metabolic activity. Congruently, flow cytometry indicates Stable GFP cells have greater polyplex uptake than LT Red-labeled cells in both cell lines. Despite these similar trends in uptake, polyplex intracellular trafficking differs in the two cell lines, as confocal imaging revealed greater polyplex/lysosome colocalization in Stable GFP U87 cells than LT Red-labeled U87 cells, while the trend was reversed in MBA-MB-231s. The level of RNA-mediated gene silencing achieved in Parental versus Stable GFP U87 and MDA-MB-231 cells agreed with the observed levels of polyplex/lysosome colocalization, supporting the established concept that endosomal escape is the rate-limiting step for RNA interference. These findings indicate that lysosomal labels can profoundly alter cellular function and cell-nanocarrier interactions, presenting critical new considerations for researchers investigating nanoparticle trafficking.

Polymersomes for Therapeutic Delivery of Protein and Nucleic Acid Macromolecules: From Design to Therapeutic Applications.

Macromolecule-based therapeutic agents, particularly proteins, antigens, monoclonal antibodies, transcription factors, nucleic acids, and gene editing enzymes, have the potential to offer cures for previously untreatable diseases. However, they present an enormous delivery challenge due to poor absorption and rapid metabolism in the body. Polymersomes have tremendous potential in delivering these agents to their desired intracellular location due to increased circulation times, decreased macromolecule degradation, and decreased immune responses. In this Review, we highlight the key factors in design, development, and improved performance of these vesicles for macromolecular delivery. The recent progress made toward preclinical application of these vesicles for protein and gene delivery is also covered.

Persistent prolate polymersomes for enhanced co-delivery of hydrophilic and hydrophobic drugs.

Self-assembled polymersomes encapsulate, protect, and deliver hydrophobic and hydrophilic drugs. Though spherical polymersomes are effective, early studies suggest that non-spherical structures may enhance specificity of delivery and uptake due to similarity to endogenous uptake targets. Here we describe a method to obtain persistent non-spherical shapes, prolates, via osmotic pressure and the effect of prolates on uptake behavior. Polyethylene glycol-b-poly(lactic acid) polymersomes change in diameter from 145 ± 6 nm to 191 ± 1 nm and increase in polydispersity from 0.05 ± 0.02 to 0.12 ± 0.01 nm after addition of 50 mM salt. Transmission and scanning electron microscopy confirm changes from spheres to prolates. Prolate-like polymersomes maintain their shape in 50 mM NaCl for seven days. Nile Red and bovine serum albumin-Fluorescein dyes are taken up in greater amounts by SH-SY5Y neural cells when encapsulated in polymersomes. Prolate polymersomes may be taken up more efficiently in neural cells than spherical polymersomes.

Development of "CLAN" Nanomedicine for Nucleic Acid Therapeutics.

Nucleic acid-based macromolecules have paved new avenues for the development of therapeutic interventions against a spectrum of diseases; however, their clinical translation is limited by successful delivery to the target site and cells. Therefore, numerous systems have been developed to overcome delivery challenges to nucleic acids. From the viewpoint of clinical translation, it is highly desirable to develop systems with clinically validated materials and controllability in synthesis. With this in mind, a cationic lipid assisted PEG-b-PLA nanoparticle (CLAN) is designed that is capable of protecting nucleic acids via encapsulation inside the aqueous core, and delivers them to target cells, while maintaining or improving nucleic acid function. The system is formulated from clinically validated components (PEG-b-PLA and its derivatives) and can be scaled-up for large scale manufacturing, offering potential for its future use in clinical applications. Here, the development and working mechanisms of CLANs, the ways to improve its delivery efficacy, and its application in various disease treatments are summarized. Finally, a prospective for the further development of CLAN is also discussed.

A capillary electrophoresis-based enzyme assay for kinetics and inhibition studies of carbonic anhydrase.

In the current study, capillary electrophoresis (CE)-based enzyme assay for characterization and inhibition study of bovine carbonic anhydrase II (bCA II) was developed. The developed method is the first CE assay for carbonic anhydrase (CA). The method was optimized in order to get short analysis time, minimal sample volume consumption, and high resolution of substrate and product. The CE conditions were optimized as follows: fused-silica capillary (30 cm effective length×75 µm i.d.), pressure injection for 5s, 20mM sodium borate buffer (pH 9.0), constant voltage of 15 kV, constant capillary temperature of 25 °C, and detection at 260 nm. For precise measurements, uridine was used as an internal standard during optimization of the CE methods. The limits of detection and quantification for p-nitrophenyl acetate (p-NPA) were 3.01 and 9.12 µM, respectively, whereas for p-nitrophenolate they were 2.05 and 6.22 µM, respectively. The performance of the developed method was confirmed by determination of kinetic parameters (i.e., K(m) and V(max) of bCA for p-NPA); the inhibition constant (K(i)) was determined for furosemide, a standard inhibitor of CA. The new method proved to be fast and efficient, and it can be used for the investigation of inhibitors of all isoforms of CAs.

Punicalagin, a pomegranate polyphenol sensitizes the activity of antibiotics against three MDR pathogens of the Enterobacteriaceae.

BACKGROUND: Multidrug resistance (MDR) in the family Enterobacteriaceae is a perniciously increasing threat to global health security. The discovery of new antimicrobials having the reversing drug resistance potential may contribute to augment and revive the antibiotic arsenal in hand. This study aimed to explore the anti-Enterobacteriaceae capability of bioactive polyphenols from Punica granatum (P. granatum) and their co-action with antibiotics against clinical isolates of Enterobacteriaceae predominantly prevalent in South Asian countries. METHODS: The Kandhari P. granatum (Pakistani origin) extracts were tested for anti-Enterobacteriaceae activity by agar well diffusion assay against MDR Salmonella enterica serovar Typhi, serovar Typhimurium and Escherichia coli. Predominant compounds of active extract were determined by mass spectrometry and screened for bioactivity by agar well diffusion and minimum inhibitory concentration (MIC) assay. The active punicalagin was further evaluated at sub-inhibitory concentrations (SICs) for coactivity with nine conventional antimicrobials using a disc diffusion assay followed by time-kill experiments that proceeded with SICs of punicalagin and antimicrobials. RESULTS: Among all P. granatum crude extracts, pomegranate peel methanol extract showed the largest inhibition zones of 25, 22 and 19 mm, and the MICs as 3.9, 7.8 and 7.8 mg/mL for S. typhi, S. typhimurium and E. coli, respectively. Punicalagin and ellagic acid were determined as predominant compounds by mass spectrometry. In plate assay, punicalagin (10 mg/mL) was active with hazy inhibition zones of 17, 14, and 13 mm against S. typhi, S. typhimurium and E. coli, respectively. However, in broth dilution assay punicalagin showed no MIC up to 10 mg/mL. The SICs 30 µg, 100 µg, and 500 µg of punicalagin combined with antimicrobials i.e., aminoglycoside, ß-lactam, and fluoroquinolone act in synergy against MDR strains with % increase in inhibition zone values varying from 3.4 ± 2.7% to 73.8 ± 8.4%. In time-kill curves, a significant decrease in cell density was observed with the SICs of antimicrobials/punicalagin (0.03-60 µg/mL/30, 100, 500 µg/mL of punicalagin) combinations. CONCLUSIONS: The P. granatum peel methanol extract exhibited antimicrobial activity against MDR Enterobacteriaceae pathogens. Punicalagin, the bacteriostatic flavonoid act as a concentration-dependent sensitizing agent for antimicrobials against Enterobacteriaceae. Our findings for the therapeutic punicalagin-antimicrobial combination prompt further evaluation of punicalagin as a potent activator for drugs, which otherwise remain less or inactive against MDR strains.

Advances in immobilized enzyme microbioreactors in capillary electrophoresis.

Miniaturized bioanalytical systems are increasingly being used in the field of biochemical research. Immobilized enzyme microbioreactors in capillary electrophoresis (CE) have been constructed and used to fulfill the increasing demands for miniaturized bioanalytical systems. This manipulation permits low sample consumption, reduced costs, short analysis times and efficient analyses. This review provides an overview of the distinct characteristics of immobilized microbioreactors in CE. After an introduction on miniaturized microreactors, the various methods of enzyme immobilization will be discussed. The emphasis will be on two common constructions of microreactors in CE, i.e. CE-coupled microreactors, and microreactors directly integrated into the CE capillary. Such microbioreactors offer straightforward automation of reaction steps followed by separation in the same capillary.

Development of a fast and efficient CE enzyme assay for the characterization and inhibition studies of α-glucosidase inhibitors.

The inhibition of the α-glucosidase enzyme plays an important role in the treatment of diabetes mellitus. We have established a highly sensitive, fast, and convenient CE method for the characterization of the enzyme and inhibition studies of α-glucosidase inhibitors. The separation conditions were optimized; the pH value and concentration of the borate-based separation buffer were optimized in order to achieve baseline separation of p-nitrophenyl-α-d-glucopyranoside and p-nitrophenolate. The optimized method using 25 mM tetraborate buffer, pH 9.5, was evaluated in terms of repeatability, LOD, LOQ, and linearity. The LOD and LOQ were 0.32 and 1.32 µM for p-nitrophenyl-α-D-glucopyranoside and 0.83 and 3.42 µM for p-nitrophenolate, respectively. The value of the Michaelis-Menten constant (K(m)) determined for the enzyme is 0.61 mM, which is in good agreement with the reported data. The RSDs (n = 6) for the migration time was 0.67 and 1.83% for substrate and product, respectively. In the newly established CE method, the separation of the reaction analytes was completed in <4 min. The developed CE method is rapid and simple for measuring enzyme kinetics and for assaying inhibitors.

Synergistic Enhancement of Near-Infrared Emission in CsPbCl3 Host via Co-Doping with Yb3+ and Nd3+ for Perovskite Light Emitting Diodes.

Perovskite nanocrystals (PeNCs) have emerged as a promising class of luminescent materials offering size and composition-tunable luminescence with high efficiency and color purity in the visible range. PeNCs doped with Yb3+ ions, known for their near-infrared (NIR) emission properties, have gained significant attention due to their potential applications. However, these materials still face challenges with weak NIR electroluminescence (EL) emission and low external quantum efficiency (EQE), primarily due to undesired resonance energy transfer (RET) occurring between the host and Yb3+ ions, which adversely affects their emission efficiency and device performance. Herein, we report the synergistic enhancement of NIR emission in a CsPbCl3 host through co-doping with Yb3+/Nd3+ ions for perovskite LEDs (PeLEDs). The co-doping of Yb3+/Nd3+ ions in a CsPbCl3 host resulted in enhanced NIR emission above 1000 nm, which is highly desirable for NIR optoelectronic applications. This cooperative energy transfer between Yb3+ and Nd3+ can enhance the overall efficiency of energy conversion. Furthermore, the PeLEDs incorporating the co-doped CsPbCl3/Yb3+/Nd3+ PeNCs as an emitting layer exhibited significantly enhanced NIR EL compared to the single doped PeLEDs. The optimized co-doped PeLEDs showed improved device performance, including increased EQE of 6.2% at 1035 nm wavelength and low turn-on voltage. Our findings highlight the potential of co-doping with Yb3+ and Nd3+ ions as a strategy for achieving synergistic enhancement of NIR emission in CsPbCl3 perovskite materials, which could pave the way for the development of highly efficient perovskite LEDs for NIR optoelectronic applications.

Hesperidin identified from Citrus extracts potently inhibits HCV genotype 3a NS3 protease.

BACKGROUND: Hepatitis C virus infection is the main cause of liver ailments across the globe. Several HCV genotypes have been identified in different parts of the world. Effective drugs for combating HCV infections are available but not affordable, particularly to infected individuals from resource-limited countries. Hence, cost-effective drugs need to be developed against important HCV drug targets. As Citrus fruits naturally contain bioactive compounds with antiviral activities, the current study was designed to identify antiviral inhibitors from Citrus fruit extracts against an important drug target, NS3 protease, of HCV genotype 3a which is found predominantly in South Asian countries. METHODS: The full-length NS3 protease alone and the NS3 protease domain in fusion with the cognate NS4A cofactor were expressed in Escherichia coli, and purified by chromatographic techniques. Using the purified protein as a drug target, Citrus extracts were evaluated in a FRET assay, and active ingredients, identified using ESI-MS/MS, were docked to observe the interaction with active site residues of NS3. The best interacting compound was further confirmed through the FRET assay as the inhibitor of NS3 protease. RESULTS: Fusion of the NS3 protease domain to the NS4A cofactor significantly improved the purification yield, and NS3-NS4A was functionally more active than the full-length NS3 alone. The purified protein (NS3-NS4A) was successfully employed in a validated FRET assay to evaluate 14 Citrus fruit extracts, revealing that the mesocarp extract of Citrus paradisi, and whole fruit extracts of C. sinesis, C. aurantinum, and C. reticulata significantly inhibited the protease activity of HCV NS3 protease (IC50 values of 5.79 ± 1.44 µg/mL, 37.19 ± 5.92 µg/mL, 42.62 ± 6.89 µg/mL, and 57.65 ± 3.81 µg/mL, respectively). Subsequent ESI-MSn analysis identified a flavonoid, hesperidin, abundantly present in all the afore-mentioned Citrus extracts. Importantly, docking studies suggested that hesperidin interacts with active site residues, and acts as a potent inhibitor of NS3 protease, exhibiting an IC50 value of 11.34 ± 3.83 µg/mL. CONCLUSIONS: A FRET assay was developed using NS3-NS4A protease, which was successfully utilized for the evaluation of Citrus fruit extracts. Hesperidin, a compound present in the Citrus extracts, was identified as the main flavonoid, which can serve as a cost-effective potent inhibitor of NS3 protease, and could be developed as a drug for antiviral therapy against HCV genotype 3a.

Ultrafast charge-conversional nanocarrier for tumor-acidity-activated targeted drug elivery.

Nanocarriers with tumor-acidity-activated charge-conversional ability are of particular interest for targeted drug delivery in the field of precision nanomedicine. Nevertheless, the key challenge of this strategy is the slowness of reversing the surface charge at the tumor tissue. As a proof-of-concept, we synthesized the amphiphilic triblock polymer poly(ethylene glycol)-block-poly(2-carboxyethylacrylate)-block-poly(2-azepaneethylmethacrylate) (PEG-b-PCEA-b-PAEMA) to prepare the cisplatin-loaded nanocarrier UCC-NP/Pt. The PAEMA block at the physiological pH values was hydrophobic, which formed the core of UCC-NP/Pt. In contrast, at the tumor acidity, the tertiary amine groups of PAEMA block rapidly protonated, resulting in the ultrafast charge conversion of UCC-NP/Pt within 10 s. Such ultrafast charge-conversional effect more efficiently enhanced tumor cell internalization of nanocarriers, thus achieving targeted drug delivery, which in turn exhibited superior anticancer efficacy even in the cisplatin-resistant cells. This approach provides new avenues for tumor-acidity-activated targeted drug delivery.

Delivery of tacrolimus with cationic lipid-assisted nanoparticles for ulcerative colitis therapy.

Oral drug delivery with nanoparticles has demonstrated great potential for drugs with poor bioavailability. Efficient delivery is possible by overcoming both the mucus and epithelial barrier of the gastrointestinal tract (GIT). Cationic lipid-assisted nanoparticles (CLANs), which are composed of amphiphilic block copolymers and cationic lipids, have been well studied and have been proved beneficial for drug delivery. In this study, CLANs prepared by poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) and 1,2-dioleoyl-3-trimethylammonium-propanechloride (DOTAP) or N,N-bis(2-hydroxyethyl)-N-methyl-N-(2-cholesteryloxycarbonyl aminoethyl)ammoniumbromide (BHEM-Chol) were used for oral delivery of tacrolimus (FK506) for ulcerative colitis treatment. The average size of these nanoparticles is around 110 nm and the zeta-potential is 35 mV. These nanoparticles maintained their size in buffer solutions of pH 1.2 and 6.8, and slowly release the encapsulated drug. CLANs can be accumulated in the colon and transported through the epithelium in the colitis model by dextran sulfate sodium salt (DSS), leading to attenuation of DSS-induced colitis.

The effect of surface poly(ethylene glycol) length on in vivo drug delivery behaviors of polymeric nanoparticles.

Engineering nanoparticles of reasonable surface poly(ethylene glycol) (PEG) length is important for designing efficient drug delivery systems. Eliminating the disturbance by other nanoproperties, such as size, PEG density, etc., is crucial for systemically investigating the impact of surface PEG length on the biological behavior of nanoparticles. In the present study, nanoparticles with different surface PEG length but similar other nanoproperties were prepared by using poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) copolymers of different molecular weights and incorporating different contents of PCL3500 homopolymer. The molecular weight of PEG block in PEG-PCL was between 3400 and 8000 Da, the sizes of nanoparticles were around 100 nm, the terminal PEG density was controlled at 0.4 PEG/nm2 (or the frontal PEG density was controlled at 0.16 PEG/nm2). Using these nanoproperties well-designed nanoparticles, we demonstrated PEG length-dependent changes in the biological behaviors of nanoparticles and exhibited nonmonotonic improvements as the PEG molecular weight increased from 3400 to 8000 Da. Moreover, under the experimental conditions, we found nanoparticles with a surface PEG length of 13.8 nm (MW = 5000 Da) significantly decreased the absorption with serum protein and interaction with macrophages, which led to prolonged blood circulation time, enhanced tumor accumulation and improved antitumor efficacy. The present study will help to establish a relatively precise relationship between surface PEG length and the in vivo behavior of nanoparticles.

The effect of surface charge on oral absorption of polymeric nanoparticles.

Surface charge plays an important role in determining the interactions of nanoparticles with biological components. Substantial studies have demonstrated that surface charge affects the fate of nanoparticles after intravenous administration; however, few studies have investigated the effect of surface charge on the bioavailability and absorption of nanoparticles after oral administration. In this study, polymeric nanoparticles with a similar particle size and surface polyethylene glycol (PEG) density, but with varying surface charges (positive, negative and neutral), were developed to study the effect of surface charge on the oral absorption of polymeric nanoparticles. The nanoparticles were constructed from polyethylene glycol-block-polylactic acid (PEG-PLA) with the incorporation of lipid components with different charges. Our results suggested that the positive surface charge facilitated the cellular uptake and transport of nanoparticles through both Caco-2 cells in vitro and small intestinal epithelial cells in vivo. The positively charged nanoparticles showed a favorable distribution in the small intestine, and significantly improved the oral bioavailability. This study presents valuable information towards the design of nanoparticles for improved oral drug delivery.

Responsive Nanocarriers as an Emerging Platform for Cascaded Delivery of Nucleic Acids to Cancer.

Cascades of systemic and intracellular obstacles, including low stability in blood, little tumor accumulation, weak tumor penetration, poor cellular uptake, inefficient endosomal escape and deficient disassembly in the cytoplasm, must be overcome in order to deliver nucleic acid drugs for cancer therapy. Nanocarriers that are sensitive to a variety of physiological stimuli, such as pH, redox status, and cell enzymes, are substantially changing the landscape of nucleic acid drug delivery by helping to overcome cascaded systemic and intracellular barriers. This review discusses nucleic acid-based therapeutics, systemic and intracellular barriers to efficient nucleic acid delivery, and nanocarriers responsive to extracellular and intracellular biological stimuli to overcome individual barriers. In particular, responsive nanocarriers for the cascaded delivery of nucleic acids in vivo are highlighted. Developing novel cascaded nanocarriers that transform their physicochemical properties in response to various stimuli in a timely and spatially controlled manner for nucleic acid drug delivery holds great potential for translating the promise of nucleic acid drugs and achieving clinically successful cancer therapy.

Protection of hepatotoxicity using Spondias pinnata by prevention of ethanol-induced oxidative stress, DNA-damage and altered biochemical markers in Wistar rats.

BACKGROUND: Traditional systems of medicine use herbal drugs for hepatoprotection. Thus, the study was designed to evaluate the hepatoprotective and antioxidant effects of Spondias pinnata bark extracts against ethanol-induced liver injury in Wistar rats. METHODS: Group I animals were treated with 1 mL/kg 0.3% carboxymethyl cellulose and Group II with 12 mL/kg 50% ethanol for 8 consecutive days. Groups III-VII animals were first treated with 400 mg/kg petroleum ether extract, chloroform extract, acetone extract (AE), ethanol extract (EE), and 100 mg/kg silymarin, and then 12 mL/kg 50% ethanol orally after 2 hours pretreatment each day for 8 consecutive days. Six hours after the last dose, blood was withdrawn. The hepatoprotective activity was assessed by several biochemical and antioxidant parameters. It was accomplished by the histopathology and DNA fragmentation study of liver tissues. RESULTS: Treatment with S. pinnata extracts, mainly AE and EE significantly (p < 0.05-0.01) and dose-dependently prevented the ethanol-induced increase in serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, cholesterol, bilirubin, and malondialdehyde, and decrease in reduced glutathione, catalase, superoxide dismutase, and albumin. They also attenuated the ethanol-induced DNA damage. Hepatoprotective potential of the extract was less than that of standard drug silymarin. Results of the study were well supported by the histopathological observations. CONCLUSION: S. pinnata extracts AE and EE possess a potent hepatoprotective effect against ethanol-induced liver injury in Wistar rats, and protect them from hepatotoxicity by prevention of ethanol-induced oxidative stress, DNA-damage and altered biochemical markers.

Is a lateral view essential in management of hip fracture?

INTRODUCTION: Neck of femur accounts to about 86,000 cases per annum in UK. AP and lateral radiographs form an essential investigation in planning the management of these fractures. Recently it has been suggested that lateral view does not provide any additional information in majority of the cases. MATERIALS AND METHODS: We looked retrospectively at 25 consecutive radiographs with intracapsular and extracapsular fracture neck of femur each presenting to our department between May 2010 and January 2011. These radiographs were put on the CD in 2 folders as AP and lateral. It was reviewed by 2 observers who suggested their preferred treatment. The results were compared for the intra observer agreement to assess the necessity of the lateral view of the radiographs. We also compared the treatment options with the gold standard. RESULTS: Our results showed that lateral view did not make any difference in the management in majority of the cases with excellent agreement based on kappa statistics. CONCLUSION: We feel that the lateral view does not make any difference in most of the cases as shown by a good intraobserver agreement.