Computational prediction of potential vaccine candidates from tRNA encoded peptides(tREP) using a bioinformatic workflow and molecular dynamics validations.

Transfer RNAs (tRNA) are non-coding RNAs. Encouraged by biological applications discovered for peptides derived from other non-coding genomic regions, we explore the possibility of deriving epitope-based vaccines from tRNA encoded peptides (tREP) in this study. Epitope-based vaccines have been identified as an effective strategy to mitigate safety and specificity concerns observed in vaccine development. In this study, we explore the potential of tREP as a source for epitope-based vaccines for virus pathogens. We present a computational workflow that uses verified data sources and community-validated predictive tools to produce a ranked list of plausible epitope-based vaccines starting from tRNA sequences. The top epitope, bound to the predicted HLA molecule, for the virus pathogen is computationally validated through 200 ns molecular dynamics (MD) simulations followed by binding free energy calculations. The simulation results indicate that two tRNA encoded epitope-based vaccines, RRHIDIVV and IMVRFSAE for Mamastrovirus 3 and Norovirus GII, respectively, are likely candidates. Peptides originating from tRNAs provide unexplored opportunities for vaccine design. Encouraged by our previous experimental study, which established the inhibitory properties of tREPs against infectious parasites, we have proposed a computationally validated set of peptides derived from tREPs as vaccines for viral pathogens.

Characterization of a Myeloid Differentiation Factor 2-Derived Peptide that Facilitates THP-1 Macrophage-Mediated Phagocytosis of Gram-Negative Bacteria.

Myeloid differentiation factor 2 (MD2), the TLR4 coreceptor, has been shown to possess opsonic activity and has been implicated in phagocytosis and intracellular killing of Gram-negative bacteria. However, any MD2 protein segment involved in phagocytosis of Gram-negative bacteria is not yet known. A short synthetic MD2 segment, MD54 (amino acid regions 54 to 69), was shown to interact with a Gram-negative bacterial outer membrane component, LPS, earlier. Furthermore, the MD54 peptide induced aggregation of LPS and facilitated its internalization in THP-1 cells. Currently, it has been investigated if MD2-derived MD54 possesses any opsonic property and role in phagocytosis of Gram-negative bacteria. Remarkably, we observed that MD54 facilitated agglutination of Gram-negative bacteria, Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC BAA-427), but not of Gram-positive bacteria, Bacillus subtilis (ATCC 6633) and Staphylococcus aureus (ATCC 25923). The MD54-opsonized Gram-negative bacteria internalized within PMA-treated THP-1 cells and were killed over a longer incubation period. However, both internalization and intracellular killing of the MD54-opsonized Gram-negative bacteria within THP-1 phagocytes were appreciably inhibited in the presence of a phagocytosis inhibitor, cytochalasin D. Furthermore, MD54 facilitated the clearance of Gram-negative bacteria E. coli (ATCC 25922) and P. aeruginosa (ATCC BAA-427) from the infected BALB/c mice whereas an MD54 analog, MMD54, was inactive. Overall, for the first time, the results revealed that a short MD2-derived peptide can specifically agglutinate Gram-negative bacteria, act as an opsonin for these bacteria, and facilitate their phagocytosis by THP-1 phagocytes. The results suggest that the MD54 segment could have a crucial role in MD2-mediated host-pathogen interaction involving the Gram-negative bacteria.

Estimation of spectroscopic parameters and TL glow curve analysis of Eu3+-activated CaY2O4 phosphor.

The solid-state reaction method was utilised to create a down-conversion phosphor in an air environment in CaY2O4:Eu3+ nanocrystalline material. The calcination temperature was set at 1000 °C, and the sintering temperature was set at 1300 °C. Following annealing, confirmation of the crystallinity quality of the phosphor was accomplished by the use of X-ray diffraction analysis. The particle size was predicted to be 43.113 nm using Scherrer's formula. To produce down-conversion luminescence spectra, an excitation wavelength of 247 nm was applied with a fluorescence spectrophotometer. The PL got increasingly intense as the concentration of the dopant increased. The maximum intensity was measured at 2.0 mol% of Eu3+ ion, which gradually decreased as the concentration increased because of concentration quenching. To analyse spectrophotometric peak determinations, the approach developed by the Commission Internationale de l'Éclairage (CIE) was used. Thermoluminescence (TL) glow curve analysis of the CaY2O4:Eu3+-doped phosphor manufactured here revealed a wide TL centred at 225 °C, which comprised of so many peaks that may be extracted by the computerised glow curve deconvolution (CGCD) approach using glow-fit software. The associated kinetic parameters were then determined. The prepared phosphor may be useful for application in various display devices upon excitation by 247 nm; the prominent 613 nm peak of the Eu3+ ion (5D0 → 7F2) electric dipole transition features a red component. CaY2O4:Eu3+ phosphors show promise as materials for potential use in phosphor-converted white LEDs in the field of solid-state lighting technology. The linear connection that the TL glow curve has with UV dose provides evidence for its possible use in dosimetry.

Optimizing the luminescence efficiency of an europium (Eu3+) doped SrY2O4 phosphor for flexible display and lighting applications.

This research paper reports the synthesis and luminescence study of an Eu3+ activated SrY2O4 phosphor prepared by a modified solid-state reaction method with varying concentrations of Eu3+ ions (0.1-2.5 mol%). X-ray diffraction (XRD) revealed the orthorhombic structure and Fourier transform infrared spectroscopy (FTIR) methods were used to analyse the produced phosphors. Photoluminescence emission and excitation spectra were recorded for varying concentrations of Eu3+ ions, and an optimum concentration of 2.0 mol% was found to produce the highest intensity. Under 254 nm excitation the emission peaks were found to be at 580 nm, 590 nm, 611 nm and 619 nm, corresponding to transitions at 5D0 → 7F0, 5D0 → 7F1, and 5D0 → 7F2 respectively. Because of Eu3+ inherent luminosity, these emission peaks indicate radiative transitions between excited states of ions, making them useful for developing white light-emitting phosphors for optoelectronic and flexible display applications. The 1931 CIE (x, y) chromaticity coordinates were calculated from the photoluminescence emission spectra and found to be near white light emission, indicating the potential application of the prepared phosphor for light emitting diodes (white component). TL glow curve analysis was also performed for various concentrations of doping ions and UV exposure times, and a single broad peak was observed at 187 °C. Using the computerised glow curve deconvolution (CGCD) method, kinetic parameters were computed.

Intense green light emission and thermoluminescence glow curve analysis of Tb3+ -activated CaY2 O4 phosphor.

Here, the synthesis and luminescence analysis of the Tb3+ -activated phosphor were reported. The CaY2 O4 phosphors were synthesized using a modified solid-state reaction method with a variable doping concentration of Tb3+ ion (0.1-2.5 mol%). As synthesized, the phosphor was characterized using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction analysis techniques for the optimized concentration of doping ions. The prepared phosphor showed a cubic structure, and FTIR analysis confirmed functional group analysis. It was discovered that the intensity of 1.5 mol% was higher than at other concentrations after the photoluminescence (PL) excitation and emission spectra were recorded for different concentrations of doping ions. The excitation was monitored at 542 nm, and the emission was monitored at 237 nm. At 237 nm excitation, the emission peaks were found at 620 nm (5 D4 →7 F3 ), 582 nm (5 D4 →7 F4 ), 542 nm (5 D4 →7 F5 ), and 484 nm (5 D4 →7 F6 ). The 1931 CIE (x, y) chromaticity coordinates showed the distribution of the spectral region calculated from the PL emission spectra. The values of (x = 0.34 and y = 0.60) were very close to dark green emission. Therefore, the produced phosphor would be very useful for light-emitting diode (green component) applications. Thermoluminescence glow curve analysis for various concentrations of doping ions and various ultraviolet (UV) exposure times was carried out, and a single broad peak was found at 252°C. The computerized glow curve deconvolution method was used to obtain the related kinetic parameters. The prepared phosphor exhibited an excellent response to UV dose and could be useful for UV ray dosimetry.

Introduction of a ß-leucine residue instead of leucine9 and glycine10 residues in Temporin L for improved cell selectivity, stability and activity against planktonic and biofilm of methicillin resistant S. aureus.

Leucine and glycine residues, at the 9th and 10th positions of helical domain of naturally occurring antimicrobial peptide (AMP), Temporin L were substituted with an unnatural amino acid, ß-leucine (homovaline) to improve its serum protease stability, haemolytic/cytotoxic properties and reduce the size to some extent. The designed analogue, L9ßl-TL showed either equal or improved antimicrobial activity to TL against different microorganisms including the resistant strains. Interestingly, L9ßl-TL also exhibited lower haemolytic and cytotoxic activities against human red blood cells and 3T3 cells, respectively. Moreover, L9ßl-TL showed antibacterial activity in presence of 25% (v/v) human serum and showed resistance against proteolytic cleavage in presence of it that suggested the serum protease stability of the TL-analogue. L9ßl-TL exhibited un-ordered secondary structures in both bacterial and mammalian membrane mimetic lipid vesicles as compared to the helical structures of TL in these environments. However, tryptophan fluorescence studies demonstrated more selective interaction of L9ßl-TL with bacterial membrane mimetic lipid vesicles in comparison to non-selective interactions of TL with both kinds of lipid vesicles. Membrane depolarization studies with live MRSA and bacterial membrane-mimetic lipid vesicles suggested a membrane-disrupting mode of action of L9ßl-TL. L9ßl-TL showed faster bactericidal mechanism compared to TL against MRSA. Interestingly, L9ßl-TL was found as more potent than TL either in inhibiting biofilm formation or in eradicating the mature biofilm formed by MRSA. Overall, the present work demonstrates a simple and useful strategy to design of an analogue of TL, with minimal modifications while maintaining its antimicrobial activity with lesser toxicity and higher stability which could be attempted for other AMPs as well.

Effect of Multiple Doses of Sparsentan on the Single-Dose Pharmacokinetics of Dapagliflozin: An Open-Label Drug-Drug Interaction Study in Healthy Adults.

Sparsentan is a single-molecule dual antagonist of the endothelin type A receptor and angiotensin II type 1 receptor under investigation for the treatment of focal segmental glomerulosclerosis and immunoglobulin A nephropathy. Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, has recently been indicated in chronic kidney disease. Sparsentan may be considered for concomitant use with dapagliflozin. The purpose of this open-label, 1-sequence crossover study was to determine whether drug-drug interactions between sparsentan and dapagliflozin affect dapagliflozin pharmacokinetics (PK). In addition, exposure to the inactive metabolite of dapagliflozin, dapagliflozin-3-O-glucuronide, was used to evaluate the effect of sparsentan on the primary metabolizing enzyme of dapagliflozin, uridine 5'-diphospho-glucuronosyltransferase 1A9. The study included 22 healthy adults treated with 10 mg of dapagliflozin on day 1, and 800 mg/day of sparsentan on days 5-14, with a 10-mg dose of dapagliflozin coadministered on day 11. PK samples were taken for dapagliflozin, dapagliflozin-3-O-glucuronide, and sparsentan before and after treatment throughout the study. Steady-state concentrations of sparsentan following daily dosing did not affect the PK of single-dose dapagliflozin in healthy adults. Dapagliflozin-3-O-glucuronide PK suggests a minimal effect of sparsentan on metabolism of dapagliflozin by uridine 5'-diphospho-glucuronosyltransferase 1A9. No deaths, serious adverse events, or unusual safety signals occurred. Results suggest dapagliflozin PK is not affected by sparsentan daily dosing.

A Mechanistic Review on Phytomedicine and Natural Products in the Treatment of Diabetes.

Diabetes mellitus is a metabolic syndrome of excess glucose levels in the blood. It may be due to glucose intolerance by the tissues and inadequate insulin production from pancreatic ß- cells. However, diabetic complication includes cardiovascular and kidney diseases, eye, skin, and foot complications, and neuropathy. The intention behind writing this article was to gather recent information regarding the use of ancient traditional medicinal plants having recent importance in treating diabetes. Several therapies are available for curing the condition based on severity and type of diabetes. Although pharmacological treatments are effective and economical, drugs are associated with unwanted side effects and physiological complications on long-term use. Interestingly, herbs and herbal plants have been used since ancient times against diabetes worldwide. Its importance still exists due to medicinal plants' effectiveness and safety profile in treating various diseases. In this article, we searched online databases, including PUBMED, SCOPUS, MEDLINE, and traditional resources, for collecting information regarding the use of plants against diabetes. We described the pathophysiology of the disease and incorporated plant sources and their chemical constituents responsible for antidiabetic activity with their mechanism in reducing blood glucose levels. The present article may be very helpful for researchers and professionals whose work is inclined towards diabetes and in search of lead compounds for the development of a suitable drug.

10-Residue MyD88-Peptide Adopts ß-Sheet Structure, Self-Assembles, Binds to Lipopolysaccharides, and Rescues Mice from Endotoxin-Mediated Lung-Infection and Death.

Naturally occurring cationic antimicrobial peptides (AMPs) mostly adopt α-helical structures in bacterial membrane mimetic environments. To explore the design of novel ß-sheet AMPs, we identified two short cationic amphipathic ß-strand segments from the crystal structure of the innate immune protein, MyD88. Interestingly, of these, the 10-residue arginine-valine-rich synthetic MyD88-segment, KRCRRMVVVV (M3), exhibited ß-sheet structure when bound to the outer membrane Gram-negative bacterial component, LPS. Isothermal titration calorimetric data showed that M3 bound to LPS with high affinity, and the interaction was hydrophobic in nature. Supporting these observations, computational studies indicated strong interactions of multiple and consecutive valine residues of M3 with the acyl chain of LPS. Moreover, M3 adopted nanosheet and nanofibrillar structure in 25% acetonitrile/water and isopropanol, respectively. M3 showed substantial antibacterial activities against both Gram-positive and Gram-negative bacteria which it appreciably retained in the presence of human serum and physiological salts. M3 was non-hemolytic against human red blood cells and non-cytotoxic to 3T3 cells up to 200 µM and to mice in vivo at a dose of 40 mg/kg. Furthermore, M3 neutralized LPS-induced pro-inflammatory responses in THP-1 cells and rat bone marrow-derived macrophages. Consequently, M3 attenuated LPS-mediated lung inflammation in mice and rescued them (80% survival at 10 mg/kg dose) against a lethal dose of LPS. The results demonstrate the identification of a 10-mer LPS-interacting, ß-sheet peptide from MyD88 with the ability to form nanostructures and in vivo activity against LPS challenge in mice. The identified M3-template provides scope for designing novel bioactive peptides with ß-sheet structures and self-assembling properties.

A stitch in time saves nine: All about pediatric facial fracture.

Fractures of the pediatric craniofacial skeleton can be challenging to engage in. The initial injury and subsequent treatment can cause long-term growth disturbances yielding problematic secondary deformities. It is important that clinicians involved in the care of these patients understand the differences between children and adult fracture patterns and understand the potential long-term effects on the growth of the pediatric skeleton and how to manage these problems when they occur.

Impact of age and gender disparity on CD4+ cell counts to control disease progression using specific HAART in HIV-1 positive patients: A case-control study.

BACKGROUND: Highly Active Antiretroviral Therapy (HAART) is composed of several drugs in the antiretroviral class to better treat human immunodeficiency virus type 1 (HIV-1) patients. The estimation of CD4+ T cell counts and HIV-1 viral load in plasma is required to evaluate the treatment success of a specific HAART. METHODOLOGY: The study included the effects of NRTIs (nucleoside reverse transcriptase inhibitors) and novel protease inhibitors (HAART) on normal control subjects and HIV-1 positive subjects from SGPGIMS, Lucknow, with different age groups and genders. Furthermore, the study was conducted by the estimation of HIV through ELISA, measurement of absolute CD4+ cell count, and the measurement of viral load through qRT-PCR. Furthermore, NRTIs (Retrovir and Epivir) were administered orally one tablet daily in the morning followed by newly FDA-approved protease inhibitors (fosamprenavir and darunavir) orally in the evening at the same dose. Furthermore, CD4+T cell counts and HIV-1 viral load were investigated and correlated in patients with different genders and age groups. RESULT: Administration of NRTIs and novel protease inhibitors (HAART) in HIV patients had a significant effect on the CD4+ cell count in various age intervals among males and females. The mean comparison of viral load distribution based on gender in CD4 +ve patients in the case group exhibited a viral load higher in females compared to males, indicating a statistically significant difference between males and females (p<0.05). A notable association between virological and immunological parameters was observed with a reciprocal relationship between viral load and CD4 cell count in CD4 +ve patients, demonstrating multiple correlation coefficients with an R-value of 0.853. CONCLUSION: The administration of specific HAART (NRTIs and novel protease inhibitors) in HIV patients had a notable improvement in the CD4+ cell count and viral load with significant age and gender disparity.

Spermine-Conjugated Short Proline-Rich Lipopeptides as Broad-Spectrum Intracellular Targeting Antibacterial Agents.

Toward the design of new proline-rich peptidomimetics, a short peptide segment, present in several proline-rich antimicrobial peptides (AMPs), was selected. Fatty acids of varying lengths and spermine were conjugated at the N- and C-terminals of the peptide, respectively. Spermine-conjugated lipopeptides, C10-PR-Spn and C12-PR-Spn, exhibited minimum inhibitory concentrations within 1.5-6.2 µM against the tested pathogens including resistant bacteria and insignificant hemolytic activity against human red blood cells up to 100 µM concentrations and demonstrated resistance against trypsin digestion. C10-PR-Spn and C12-PR-Spn showed synergistic antimicrobial activity against multidrug-resistant methicillin-resistant Staphylococcus aureus with several tested antibiotics. These lipopeptides did not permeabilize bacterial membrane-mimetic lipid vesicles or damage the Escherichia coli membrane like the nonmembrane-lytic AMP, buforin-II. The results suggested that C10-PR-Spn and C12-PR-Spn could interact with the 70S ribosome of E. coli and inhibit its protein synthesis. C10-PR-Spn and C12-PR-Spn demonstrated superior clearance of bacteria from the spleen, liver, and kidneys of mice, infected with S. aureus ATCC 25923 compared to levofloxacin.

Tandem Repeat of a Short Human Chemerin-Derived Peptide and Its Nontoxic d-Lysine-Containing Enantiomer Display Broad-Spectrum Antimicrobial and Antitubercular Activities.

To design novel antimicrobial peptides by utilizing the sequence of the human host defense protein, chemerin, a seven-residue amphipathic stretch located in the amino acid region, 109-115, was identified, which possesses the highest density of hydrophobic and positively charged residues. Although this 7-mer peptide was inactive toward microorganisms, its 14-mer tandem repeat (Chem-KVL) was highly active against different bacteria including methicillin-resistant Staphylococcus aureus, a multidrug-resistant Staphylococcus aureus strain, and slow- and fast-growing mycobacterial species. The selective enantiomeric substitutions of its two l-lysine residues were attempted to confer cell selectivity and proteolytic stability to Chem-KVL. Chem-8dK with a d-lysine replacement in its middle (eighth position) showed the lowest hemolytic activity against human red blood cells among Chem-KVL analogues and maintained high antimicrobial properties. Chem-8dK showed in vivo efficacy against Pseudomonas aeruginosa infection in BALB/c mice and inhibited the development of resistance in this microorganism up to 30 serial passages and growth of intracellular mycobacteria in THP-1 cells.

Involvement of mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) in endothelial dysfunction associated with pulmonary hypertension.

AIMS: Increased proliferation, inflammation, and endothelial microparticle (EMP) generation in the pulmonary vasculature lead to endothelial dysfunction in pulmonary hypertension (PH). Interestingly, MK2, a downstream of p38MAPK, is a central regulator of inflammation, proliferation, and EMP generation in cardiovascular diseases. However, the role of MK2 in pulmonary endothelial dysfunction remains unexplored. MAIN METHODS: The Human Pulmonary Artery Endothelial cells (HPAECs) were exposed to hypoxia (1% O2) for 72 h, and MK2 inhibition was achieved by siRNA treatment. Western blotting, qualitative RT-PCR, immunocytochemistry, flow cytometry and enzyme-linked immunoassays were conducted to study pathological alterations and molecular mechanisms. Neoangiogenesis was studied using cell migration and tubule formation assays. For in vivo study, Male Sprague Dawley rats and MK2 knock-out mice with littermate control were treated with monocrotaline (MCT) 60 mg/kg and 600 mg/kg, respectively (s.c. once in rat and weekly in mice) to induce PH. MMI-0100 (40 µg/kg, i.p. daily for 35 days), was administered in rats to inhibit MK2. KEY FINDINGS: MK2 inhibition significantly decreased inflammation, cell proliferation, apoptosis resistance, and improved mitochondrial functions in hypoxic HPAECs. Hypoxia promoted cell migration, VEGF expression, and angiogenesis in HPAECs, which were also reversed by MK2 siRNA. MK2 inhibition decreased EMP generation and increased the expression of p-eNOS in hypoxic HPAECs, a marker of endothelial function. Furthermore, MK2 deficiency and inhibition both reduced the EMP generation in mice and rats, respectively. SIGNIFICANCE: These findings proved that MK2 is involved in endothelial dysfunction, and its inhibition may be beneficial for endothelial function in PH.

Comparative Evaluation of Changes in Microflora in Delayed and Immediate Implant Placement: An In vivo Study.

AIM: This study is aimed to compare and evaluate the changes in the microflora in immediate and delayed placed implants. MATERIALS AND METHODS: In this study, the implant site sample was taken and assessed during different phases of treatment for delayed and immediate implants. They were looked for Streptococcus, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, and Fusobacterium nucleatum. RESULTS: The results showed that Streptococci were found in a higher number in all the phases of the treatment. The presence of pathogenic organisms such as P. gingivalis and Fusobacterium, in considerable amounts, was seen in both the groups. CONCLUSION: Thus, we conclude that implant mode of placement, delayed or immediate placement does not alter the flora of the oral cavity. Organisms present remains the same in all the phase of the treatment. To prevent the disease, one must continuously monitor the implant, with the increasing age changes, the microflora is continually changing in the oral cavity. The periodontal health should be assessed before the placement of the implant, followed by follow-ups after a set period for a better prognosis.

Efficacy of Transdermal Diclofenac Patch and Ketoprofen Patch as Postoperative Analgesia after Extraction of First Premolars Bilaterally in Both Arches for Orthodontic Purpose: A Comparative Study.

AIM: The aim of the study was to compare the efficacy of transdermal diclofenac patch with ketoprofen patch as postoperative analgesia after extraction of first premolars bilaterally in both arches for orthodontic purpose. MATERIALS AND METHODS: A split-mouth technique was used in 52 patients with the age group of 15-25 years for extracting maxillary and mandibular first premolars bilaterally for orthodontic reason. A single ketoprofen patch was used after the extraction of premolars from first and fourth quadrant, whereas for the extraction of second and third quadrant premolars, diclofenac patch was used. All the extractions were performed under local anesthesia. The data were compiled and statistically analyzed using the student's t-test. RESULTS: Mean visual analog scale score for diclofenac and ketoprofen patch was 2.05 (0.75) and 1.09 (0.3), respectively. Thirteen patients required additional medication (25%) and 1 (1.9%) patient with diclofenac and ketoprofen patch, respectively. No major complication or adverse effects were observed in any of the groups. CONCLUSION: Both diclofenac and ketoprofen transdermal patches are helpful in relieving pain after orthodontic extraction. Patients with diclofenac patch required more additional analgesia within 24 h compared to that with ketoprofen patch. None of the drugs showed any significant adverse effects and were well tolerated by the patients.

Simulated physiological oocyte maturation (SPOM) improves developmental competence of in vitro produced goat embryos.

The effect of simulated physiological oocyte maturation on the developmental competence, reactive oxygen species production and apoptosis rate of in vitro produced goat embryos were studied in the present experiment. Oocytes and spermatozoa were recovered from ovaries and epididymis, respectively, procured from a local small animal abattoir. The oocytes aspirated from the ovaries were allocated into two groups, control (subjected to routine in vitro maturation, fertilization and culture) and simulated physiological oocyte maturation (SPOM) group (subjected to prematuration, followed by routine in vitro maturation, fertilization and culture). The SPOM group showed a significantly (p < 0.05) higher maturation and blastocyst rates (90.60 ± 0.46% and 29.09 ± 2.59%, respectively) as compared to the control group (85.29 ± 0.98% and 24.09 ± 1.08%). The intensity of reactive oxygen species of the embryos in the control group (14.98 ± 0.83 pixels/embryo) was significantly (p < 0.05) higher than the SPOM group (9.60 ± 0.76 pixels/embryo). The apoptosis rate was also significantly (p < 0.05) higher in the embryos of the control group (9.18 ± 1.07%) as compared to the SPOM group (5.71 ± 0.90%). In conclusion, the simulated physiological oocyte maturation system significantly increases the developmental competence of the oocytes and decreases the intensity of reactive oxygen species and embryonic apoptosis in abattoir derived goat embryos.

Control Release of Adenosine Potentiate Osteogenic Differentiation within a Bone Integrative EGCG-g-NOCC/Collagen Composite Scaffold toward Guided Bone Regeneration in a Critical-Sized Calvarial Defect.

The regeneration of critical-sized bone defects with biomimetic scaffolds remains clinically challenging due to avascular necrosis, chronic inflammation, and altered osteogenic activity. Two confounding mechanisms, efficacy manipulation, and temporal regulation dictate the scaffold's bone regenerative ability. Equally critical is the priming of the mesenchymal stromal cells (MSCs) toward lineage-specific differentiation into bone-forming osteoblast, which particularly depends on varied mechanochemical and biological cues during bone tissue regeneration. This study sought to design and develop an optimized osteogenic scaffold, adenosine/epigallocatechin gallate-N,O-carboxymethyl chitosan/collagen type I (AD/EGCG-g-NOCC@clgn I), having osteoinductive components toward swift bone regeneration in a calvarial defect BALB/c mice model. The ex vivo findings distinctly establish the pro-osteogenic potential of adenosine and EGCG, stimulating MSCs toward osteoblast differentiation with significantly increased expression of alkaline phosphatase, calcium deposits, and enhanced osteocalcin expression. Moreover, the 3D matrix recapitulates extracellular matrix (ECM) properties, provides a favorable microenvironment, structural support against mechanical stress, and acts as a reservoir for sustained release of osteoinductive molecules for cell differentiation, proliferation, and migration during matrix osteointegration observed. Evidence from in vivo experiments, micro-CT analyses, histology, and histomorphometry signify accelerated osteogenesis both qualitatively and quantitatively: effectual bone union with enhanced bone formation and new ossified tissue in 4 mm sized defects. Our results suggest that the optimized scaffold serves as an adjuvant to guide bone tissue regeneration in critical-sized calvarial defects with promising therapeutic efficacy.

Clinical and biochemical profile of scrub typhus patients at a tertiary care hospital in Northern India.

BACKGROUND: Scrub typhus is a neglected rickettsial disease in India. Every year, we are facing outbreaks of Scrub typhus after Monsoon season. Patients present with a wide clinical spectrum ranging from pyrexia of unknown origin to multiple organ dysfunction. Some of these clinical features overlap with presentation of other tropical infections prevalent in Indian subcontinent, which leads to diagnostic dilemma and delay in diagnosis. Hence, we planned this study to know the demographic, clinical and biochemical profile of scrub typhus patients. METHODS: This was an observational study conducted in department of Medicine, King George's Medical University Lucknow, India a leading tertiary care hospital of Northern India. All scrub typhus patients were evaluated by detailed history, examination and laboratory tests. RESULTS: We enrolled 52 patients in our study. The mean age of the patients was 35.17 ± 16.90 years with majority (82.7%) of patients from rural background. All the patients had fever with an average duration of 9.6 ± 2 days. Most of the patients developed hepatitis (69.2%) followed by acute encephalitis syndrome (47%), acute kidney injury (23.1%) and acute respiratory failure (19.2%). Eschar was found in 11 patients (21.2%). CONCLUSION: Scrub typhus is often misdiagnosed or diagnosed late due to its wide clinical spectrum overlapping with clinical presentation of other commonly prevalent tropical diseases. One should always consider the differential diagnosis of scrub typhus while evaluating a young febrile patient of rural background, with features of single or multiple organ dysfunction and laboratory findings of leucocytosis, thrombocytopenia and elevation of transaminases.

Self-Assembling Nano-Globular Peptide from Human Lactoferrin Acts as a Systemic Enhancer of Bone Regeneration: A Novel Peptide for Orthopedic Application.

A technology for systemic and repeated administration of osteogenic factors for orthopedic use is an unmet medical need. Lactoferrin (∼80 kDa), present in milk, is known to support bone growth. We discovered a lactoferrin-mimetic peptide, LP2 (an 18-residue fragment from the N-terminus of the N-lobe of human lactoferrin), which self-assembles into a nano-globular assembly with a ß-sheet structure in an aqueous environment. LP2 is non-hemolytic and non-cytotoxic against human red blood cells and 3T3 fibroblasts, respectively, and appreciably stable in the human serum. LP2 through the bone morphogenetic protein-dependent mechanism stimulates osteoblast differentiation more potently than the full-length protein as well as the osteoblastic production of osteoprotegerin (an anti-osteoclastogenic factor). Consequently, daily subcutaneous administration of LP2 to rats and rabbits with osteotomy resulted in faster bone healing and stimulated bone formation in rats with a low bone mass more potently than that with teriparatide, the standard-of-care osteogenic peptide for osteoporosis. LP2 has skeletal bioavailability and is safe at the 15× osteogenic dose. Thus, LP2 is a novel peptide that can be administered systemically for the medical management of hard-to-heal fractures.