Safety and effectiveness of interference RNA (RNAi) based therapeutics in cardiac failure: A systematic review.

BACKGROUND: Heart failure is a major worldwide health concern and leading cause of mortality. RNAi interventions hold promise for patients resistant to conventional drugs due to their off-target effects and lack of specificity. OBJECTIVES: To examine the safety and effectiveness of RNAi therapeutics in treating heart failure. METHODS: The PubMed, Embase, Scopus and Cochrane databases were searched using appropriate keyword from inception until December 31, 2023. A total of 14 studies fulfilling predefined selection criteria were included for qualitative synthesis. RESULTS: We found that in patients with cardiac amyloidosis, patisiran and revusiran showed considerable improvements in cardiac output and left ventricular wall thickness. In animal studies, Nox2-siRNA showed effectiveness in regaining heart function. Furthermore, cardiomyocyte count and left ventricular function were improved by DUSP5 siRNA + T3 therapy and meg3 inhibition after myocardial infarction (MI). RNAi showed minimal adverse effects like peripheral neuropathy, hepatotoxicity, urinary tract infection, vaginal infection, diarrhea, abdominal pain arrhythmias, conduction disorders, and cardiotoxicity (LV wall thinning, heart failure) and improved cardiac biomarkers. CONCLUSION: RNAi therapeutics are novel treatment option for improving cardiac function because their high target specificity, ability to target genes that conventional drugs struggle to reach and potential for long-lasting effects. Further research on optimizing delivery methods, improving target specificity, evaluating long-term safety profiles and cost-effectiveness to fully realize their potential.

Chemical Profile, Antibacterial Activity and Antioxidant Activity of Bark Volatile Oil of Terminalia arjuna.

Terminalia arjuna is an evergreen medicinal plant that belongs to the Combretaceae family of flowering plants. The bark of the plant exhibits antiviral, anticancer, hypocholesterolemic, antioxidant and antimicrobial properties. In this study, composition antibacterial activity, antioxidant activity and cytotoxicity of bark oil of Terminalia Arjuna (Roxb.) were reported. Oils were extracted by microwave assisted hydrodistillation where an oil yield of 0.18% was obtained followed by the identification of 35 compounds by gas chromatography mass spectrometry. The most abundant volatiles were furfural (11.11%), isoeugenol (9.99%), p-ethylguaiacol (9.97%), α-cadinol (9.57%), and estragole (9.47%). The oil was further evaluated against ten different drug resistant strains where oil showed significant activity against all pathogens and the highest activity was found against Acinetobacter baumannii (22mm), Klebsiella pneumoniae (22mm) and Staphylococcus aureus (22mm) in a concentration-dependent manner. Antioxidant activity evaluation demonstrated 68% radical scavenging activity by the volatile oil as compared to 81% of the standard, ascorbic acid at a concentration of 1000 µg. Cytotoxicity studies were conducted to see the effect of sample on the expression level of a housekeeping gene, Glyceraldehyde 3-phosphate dehydrogenase where it did not affect the normal transcription of the gene.

Assessment of lifestyle changes in combating the COVID-19 pandemic among people of Karachi, Pakistan.

Aim: COVID-19 arose as a pandemic that wreaked havoc all over the world. Study determines lifestyle changes adopted by people of Karachi in response to COVID-19 pandemic. Methods: This was the cross-sectional study and carried out at public sector hospital and 218 participants were selected through random sampling method. Results: Lifestyle changes a statistically significant difference in nutrition (p = 0.000), physical activity (p = 0.000), workout (p = 0.000), smoking (p = 0.000), sleep hours (p = 0.000), and supplements (p = 0.000) before and during lockdown. Face masks were utilized by 38% of individuals, gloves by 19%, and social isolation was observed by 26%. 11% of participants did not follow any protocols. Conclusion: Study found significant differences in lifestyle habits such as diet, sleep, smoking and physical activity.

COVID-19 pandemic affect every day life of all people. This study results fond that there are different domain of quality life were affected. Nutrition, physical activity and smoking were associated with poor quality of life and these changes affect the mental and physical health of community people. There is need to social and medical support for people affected by COVID-19 pandemic.

Assessing the efficacy of celecoxib after tonsillectomy and/or adenoidectomy: A systematic review and meta-analysis of randomised control trials.

OBJECTIVES: Tonsillectomy and adenoidectomy are common surgical procedures that cause persistent pain, bleeding, and functional limitations. We aimed to investigate the efficacy of celecoxib compared with a placebo for managing post-tonsillectomy or adenoidectomy pain and other adverse events. DESIGN: Systematic review and meta-analysis. METHODS: We conducted a systematic literature search in the PubMed, Cochrane, and Google Scholar databases from inception until July 2023. Dichotomous outcomes have been reported as risk ratios (RR) while continuous outcomes were reported using mean differences (MD). A funnel plot was drawn to investigate publication bias. RESULTS: From 1394 records identified, 6 randomised double-blind trials comprising 591 participants undergoing tonsillectomy and/or adenoidectomy were eligible for inclusion. A high dose (400 mg) of celecoxib was effective in decreasing the pain score for 'worst pain' after the procedure (MD: -10.98, [95% CI: -11.53, -10.42], p < .01, I2 = 0%) while a low dose (200 mg) was not significantly effective (p = 0.31). For managing other outcomes such as vomiting (RR: 1.37 [95% CI: 0.69, 2.68], p = 0.37, I2 = 67%), diarrhoea (RR: 1.41, [95% CI: 0.75, 2.64], p = .29, I2 = 42%), dizziness/drowsiness (RR: 0.90, [95% CI: 0.71, 1.15], p = .48, I2 = 0%), functional recovery time (p = .74), and headache (p = .91), there was no significant difference between the group on celecoxib and the placebo group regardless of dosage. Finally, there was no significant difference (RR: 1.02, [95% CI: 0.91, 1.15], p = .69, I2 = 0%) in the effect of the intervention on minimum bleeding, moderate bleeding, and profuse bleeding. CONCLUSION: This meta-analysis provides robust evidence pooled from high-quality trials and raises questions about the efficacy of celecoxib for tonsillectomy and/or adenoidectomy, challenging existing perceptions.

Iron-doped biochar, an agricultural and environmentally beneficial fertilizer.

The utilization of agricultural waste to create value-added goods has benefited waste management while resolving cost-effectiveness and food shortage problems. Returning biochar produced from agricultural waste to the agricultural field is a sustainable method of enhancing crop production while lowering the environmental effect of typical fertilizers. It also enhances soil condition by modulating pH, soil organic carbon, water retention capacity, and soil ion exchange potential. The current work concentrated on the production of iron oxide-loaded biochar from banana peels. Pyrolysis was carried out at temperatures ranging from 400 to 500 °C. The co-precipitation technique was utilized to impregnate Fe3O4 nanoparticles on biochar, and it showed to be an effective and trustworthy method. Loading was done in situ. Characterization techniques such as XRD, FTIR, CHNS, and TGA were employed to characterize synthesized materials. Swelling ratio, water retention, absorbance, and equilibrium water content percentage were used to study the adsorption capabilities of Fe3O4-loaded biochar, soil, and raw biochar. As a consequence, Fe3O4-enriched biochar was shown to have better adsorption capability than raw biochar, which in turn showed better adsorption properties than soil. Iron-loaded biochar was employed as a fertilizer in Abelmoschus esculentus (Okra), and the results showed that it is a cost-effective, environmentally friendly fertilizer.

Extraction, structure, pharmacological activities and applications of polysaccharides and proteins isolated from snail mucus.

Snail mucus had medical applications for wound healing as early as ancient Greece and the late Han Dynasty (China). A literature search found 165 modern research papers discussing the extraction methods, chemical compositions, pharmacological activities, and applications of snail mucus. Thus, this review summarized the research progress on the extraction, structure, pharmacological activities, and applications of polysaccharides and proteins isolated from snail mucus. The extraction methods of snail mucus include natural secretion and stimulation with blunt force, spray, electricity, un-shelling, ultrasonic-assisted, and ozone-assisted. As a natural product, snail mucus mainly comprises two polysaccharides (glycosaminoglycan, dextran), seven glycoproteins (mucin, lectin), various antibacterial peptides, allantoin, glycolic acid, etc. It has pharmacological activities that encourage cell migration and proliferation, and promote angiogenesis and have antibacterial, anti-oxidative and anticancer properties. The mechanism of snail mucus' chemicals performing antibacterial and wound-healing was proposed. Snail mucus is a promising bioactive product with multiple medical applications and has great potential in the pharmaceutical and healthcare industries. Therefore, this review provides a valuable reference for researching and developing snail mucus.

Structure and functional divergence of PIP peptide family revealed by functional studies on PIP1 and PIP2 in Arabidopsis thaliana.

PAMP-induced secreted peptide (PIP), one of the small post-translationally modified peptides (PTMPs), plays a crucial role in plant development and stress tolerance. However, little is known about functional divergence among this peptide family. Here, we studied the evolution of the PIP family in 23 plant species (10 monocotyledons and 13 dicotyledons from 7 families) and their functional divergence in Arabidopsis. A total of 128 putative PIP precursors were identified and classified into two subfamilies through phylogenetic analysis. Functional studies on AtPIP1 which represents Clade I family and AtPIP2 which represents Clade II family have shown that AtPIP2 displayed stronger immunity induction activity but weaker root growth inhibition than AtPIP1 in Arabidopsis. Transcriptome analysis of Arabidopsis seedlings treated with AtPIP1 and AtPIP2 showed that differential genes for both polypeptides were significantly enriched in similar plant defense pathways. However, Co-expression and Protein-protein interaction (PPI) analysis showed that the functions of AtprePIP2 co-expressed genes were more enriched in plant defense pathways than AtprePIP1. Molecular docking results show that AtPIP1 binds to RLK7 receptor with a more stable free energy and less binding area than AtPIP2, while hydrogen bond transfer occurs at the SGP motif position. The above results suggest that the PIP family have undergone functional divergence during evolution. Collectively, this work illustrates the relationship between PIP structure and function using Arabidopsis PIP as an example, and provides new insights into the current understanding between growth inhibition and immune responses which may be correlated but not fully coupled.

Green synthesis and characterization of silver and copper nanoparticles and their use as an effective adsorbent for chromium removal and recovery from wastewater.

Chromium (Cr) is one of the hazardous heavy metals that is naturally carcinogenic and causes various health problems. Metallic nanoparticles such as silver and copper nanoparticles (Ag NPs and Cu NPs) have gained great attention because of their unique chemical, physical, and biological attributes, serving diverse and significant role in various useful and sustainable applications. In the present study, both of these NPs were synthesized by green method in which Azadirachta indica plant extract was used. These nanoparticles were characterized by using advanced instrumental techniques such as Fourier transmission infrared (FTIR), X-ray diffraction (XRD), scanning electron microscope attached with energy-dispersive spectroscopy (SEM-EDS), and elemental mapping. These environmentally friendly nanoparticles were utilized for the batch removal of Cr from the wastewater. For analysis of adsorption behaviour, a range of kinetic isotherm models (Freundlich, Temkin, Dubinin, and Langmuir) and kinetic models (pseudo-first-order and pseudo-second-order) were used for the Cu-NPs and Ag-NPs. Cu NPs exhibited the highest Cr removal efficiency (96%) within a contact time of 10-15 min, closely followed by Ag NPs which achieved a removal efficiency of 94% under the similar conditions. These optimal outcomes were observed at a sorbent dose of 0.5 g/L for Ag NPs and 0.7 g/L for Cu NPs. After effectively capturing Cr using these nanoparticles, the sorbates were examined through SEM-EDX analysis to observe how much Cr metal was attached to the nanoparticles, potentially for future use. The analysis found that Ag-NPs captured 18% of Cr, while Cu-NPs captured 12% from the aqueous solution. More precise experimental conditions are needed for higher Cr removal from wastewater and determination of the best conditions for industrial-level Cr reuse. Although nanomaterial exhibit high efficiency and selectivity for Cr removal and recovery from wastewater, more research is necessary to optimize their synthesis and performance for industrial-scale applications and develop efficient methods for Cr removal and recovery.

Synthesis of Iron Oxide Nanoparticles from Madhuca indica Plant Extract and Assessment of Their Cytotoxic, Antioxidant, Anti-Inflammatory, and Anti-Diabetic Properties via Different Nanoinformatics Approaches.

Recently, nanobiotechnology has attracted a lot of attention, as it is a rapidly emerging field that is still growing and developing efficient and advanced therapeutic protocols under the umbrella of nanomedicine. It can revolutionize solutions to biomedical problems by developing effective treatment protocols and therapeutics. However, focus and research are still required to make these therapeutics more effective and safer to use. In this study, iron oxide nanoparticles were synthesized from Madhuca indica extract using green synthesis protocols. The nanoparticles were further characterized based on their absorption spectrum, size, structural morphology, and other related parameters. Biological assays were also performed to evaluate biological applications for the synthesized nanoparticles. In silico analysis was performed to assess the druglike properties of synthesized nanoparticles. The results proved an optimized synthesis of the iron oxide nanoparticles with the size of 56 nm confirmed by SEM. The FTIR analysis predicted the presence of nitro and carbonyl groups in the synthesized nanoparticles. The 81% DPPH inhibition confirmed the antioxidant activity, and the 96.20% inhibition of egg albumin protein confirmed the anti-inflamatory activity. Additionally, the 73.26% inhibition of α-amylase, which was more than that of the control used, confirmed the antidiabetic activity. The ADMET analysis confirmed the synthesized nanoparticles as potential therapeutic candidates as well. However, further evaluation for safety concerns is still required to use these FeONPs as potential therapeutic agents. This study can be proved as a significant contribution to the scientific community and a gateway to the future scientists who are willing to work on nanomedicine and nanobiotechnology. ADMET analysis confirmed the synthesized nanoparticles as potential therapeutic candidates as well. However, further evaluation for safety concerns is still required to use these FeONPs and potential therapeutic agents.

Effect Of Age, Gender And Type Of Varicosity On The Post-Operative Pain Score After Seven-Day Compression Dressing After Varicose Vein Surgery.

Great saphenous vein insufficiency is linked to 80% of all remarkable lower limb varicosities. A total of 30 patients were enrolled from OPD fulfilling the inclusion criteria after the approval of the hospital's ethical committee. Patients had compression dressing for seven days after surgery. The patients were divided into two groups-Group-A (Compression dressing for two days) and Group-B (Compression dressing for seven days). Stratification of pain score was done against age, gender, and grades of varicose veins, and after dividing into groups t- test was put into use. A p 20 value ≤0.05 was contemplated to be remarkable. Thirty patients with primary varicose vein were enrolled in this study. The mean age of patients was 35.4±9.9 years. Mean pain score in these patients was 2.9±0.8 years. Pain score after seven days of compression dressing after the surgery for varicose veins depend upon the gender, age, and grades of the varicosity of the veins. It is lesser in the females, younger age groups, and in those who had initially lesser severity of the varicose veins.

Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib.

BCR-ABL1 is a fusion protein as a result of a unique chromosomal translocation (producing the so-called Philadelphia chromosome) that serves as a clinical biomarker primarily for chronic myeloid leukemia (CML); the Philadelphia chromosome also occurs, albeit rather rarely, in other types of leukemia. This fusion protein has proven itself to be a promising therapeutic target. Exploiting the natural vitamin E molecule gamma-tocotrienol as a BCR-ABL1 inhibitor with deep learning artificial intelligence (AI) drug design, this study aims to overcome the present toxicity that embodies the currently provided medications for (Ph+) leukemia, especially asciminib. Gamma-tocotrienol was employed in an AI server for drug design to construct three effective de novo drug compounds for the BCR-ABL1 fusion protein. The AIGT's (Artificial Intelligence Gamma-Tocotrienol) drug-likeliness analysis among the three led to its nomination as a target possibility. The toxicity assessment research comparing AIGT and asciminib demonstrates that AIGT, in addition to being more effective nonetheless, is also hepatoprotective. While almost all CML patients can achieve remission with tyrosine kinase inhibitors (such as asciminib), they are not cured in the strict sense. Hence it is important to develop new avenues to treat CML. We present in this study new formulations of AIGT. The docking of the AIGT with BCR-ABL1 exhibited a binding affinity of -7.486 kcal/mol, highlighting the AIGT's feasibility as a pharmaceutical option. Since current medical care only exclusively cures a small number of patients of CML with utter toxicity as a pressing consequence, a new possibility to tackle adverse instances is therefore presented in this study by new formulations of natural compounds of vitamin E, gamma-tocotrienol, thoroughly designed by AI. Even though AI-designed AIGT is effective and adequately safe as computed, in vivo testing is mandatory for the verification of the in vitro results.

Investigating Oxidative Stress Levels in Pregnant Patients Infected with Hepatitis C Virus and Bacterial Vaginosis for Better Treatment Option.

Objectives: Hepatitis C virus (HCV) and bacterial vaginosis (BV) coinfection generate sustained inflammation with bulk production of reactive oxygen species. They have the potency to cause hepatocellular carcinoma, vaginal apoptosis, disturb pregnancy, and influence drug treatment and follow-up. This case-control study aimed to compare the redox status in HCV and BV coinfection with respect to BV mono-infection among pregnant females (PFs). Methods: Blood samples and vaginal secretions were drawn from 75 PFs divided into three groups: coinfection (n = 25), monoinfection (n = 25), and control PFs (n = 25) who are presumed healthy subjects. Blood samples were analyzed for HCV detection based on conserved 5' untranslated region via real-time polymerase chain reaction and hematological parameters. Markers of oxidative stress (malondialdehyde and peroxidase) and antioxidants (catalase and superoxide dismutase) were checked in plasma as well as vaginal secretions of patients among all three groups. Results: Hematological analysis reveals that hemoglobin levels, platelets, and lymphocytes decreased significantly (p < 0.050) among the coinfection followed by mono-infection group compared to the control group. Moreover, the higher isolation frequency of pathogenic bacteria (Acinetobacter spp.) and Nugent score trend was observed among the coinfection group. Antioxidant levels were significantly lower (p < 0.050) among the vaginal secretions and blood plasma of patients having coinfection with respect to the mono-infection and control groups. While oxidative stress marker was significantly highest (p < 0.050) among vaginal secretions and blood plasma of coinfection followed by mono-infection and control group. These results validate that overall redox severity was more among the coinfection compared to the mono-infection and control groups. Conclusions: Redox indexes should be considered in early diagnosis and treatment of HCV and BV coinfection which may also facilitate the better treatment of hepatocellular carcinoma and vaginal apoptosis.

Influence of biochar and microorganism co-application on stabilization of cadmium (Cd) and improved maize growth in Cd-contaminated soil.

Cadmium (Cd) is one the leading environmental contaminants. The Cd toxicity and its potential stabilization strategies have been investigated in the recent years. However, the combined effects of biochar and microorganisms on the adsorption of Cd and maize plant physiology, still remained unclear. Therefore, this experiment was conducted to evaluate the combined effects of biochar (BC) pyrolyzed from (maize-straw, cow-manure, and poultry-manure, and microorganisms [Trichoderma harzianum (fungus) and Bacillus subtilis (bacteria)], on plant nutrient uptake under various Cd-stress levels (0, 10, and 30 ppm). The highest level of Cd stress (30 ppm) caused the highest reduction in maize plant biomass, intercellular CO2, transpiration rate, water use efficiency, stomatal conductance, and photosynthesis rate as compared to control Cd0 (0 ppm). The sole application of BC and microorganisms significantly improved plant growth, intercellular CO2, transpiration rate, water use efficiency, stomatal conductance, and photosynthesis rate and caused a significant reduction in root and shoot Cd. However, the co-application of BC and microorganisms was more effective than the sole applications. In this regard, the highest improvement in plant growth and carbon assimilation, and highest reduction in root and shoot Cd was recorded from co-application of cow-manure and combined inoculation of Trichoderma harzianum (fungus) + Bacillus subtilis (bacteria) under Cd stress. However, due to the aging factor and biochar leaching alkalinity, the effectiveness of biochar in removing Cd may diminish over time, necessitating long-term experiments to improve understanding of biochar and microbial efficiency for specific bioremediation aims.

Biallelic variants in CHST3 cause Spondyloepiphyseal dysplasia with joint dislocations in three Pakistani kindreds.

BACKGROUND: Skeletal dysplasia is a heterogeneous group of disorders. Spondyloepiphyseal dysplasias comprise one subgroup. Deficiency of carbohydrate sulfotransferase 3 has been reported in a small number of patients with recessively inherited spondyloepiphyseal dysplasia with joint dislocation, short stature and scoliosis. We report here molecular and clinical findings of affected individuals in three consanguineous Pakistani families. Affected individuals in all three families had a uniform phenotype including severe short stature, multiple dislocated joints, progressive scoliosis and facial dysmorphism. METHODS: Clinical evaluation was done for three unrelated families. Radiological survey of bones was completed for patients from two of the families. Whole exome sequencing index patients from each family was performed followed by Sanger sequencing for validation of segregation of identified variants in respective families. In-silico analysis for determining pathogenicity of identified variants and conservation was done. RESULTS: Whole-exome sequencing revealed biallelic variants c.590 T > C;p.(Leu197Pro), c.603C > A;p.(Tyr201Ter) and c.661C > T;p.(Arg221Cys) in CHST3 (NM_004273.5) in the three families with eight, five and two affected individuals, respectively. Contrary to previous reports, affected individuals in none of the families exhibited a hearing loss. CONCLUSION: We describe genotypic and phenotypic findings of three unrelated families with spondyloepiphyseal dysplasia. Our study confirms phenotypic variability and adds to the genotypic spectrum of spondyloepiphyseal dysplasia.

Biallelic KIF24 Variants Are Responsible for a Spectrum of Skeletal Disorders Ranging From Lethal Skeletal Ciliopathy to Severe Acromesomelic Dysplasia.

Skeletal dysplasias comprise a large spectrum of mostly monogenic disorders affecting bone growth, patterning, and homeostasis, and ranging in severity from lethal to mild phenotypes. This study aimed to underpin the genetic cause of skeletal dysplasia in three unrelated families with variable skeletal manifestations. The six affected individuals from three families had severe short stature with extreme shortening of forelimbs, short long-bones, and metatarsals, and brachydactyly (family 1); mild short stature, platyspondyly, and metaphyseal irregularities (family 2); or a prenatally lethal skeletal dysplasia with kidney features suggestive of a ciliopathy (family 3). Genetic studies by whole genome, whole exome, and ciliome panel sequencing identified in all affected individuals biallelic missense variants in KIF24, which encodes a kinesin family member controlling ciliogenesis. In families 1 and 3, with the more severe phenotype, the affected subjects harbored homozygous variants (c.1457A>G; p.(Ile486Val) and c.1565A>G; p.(Asn522Ser), respectively) in the motor domain which plays a crucial role in KIF24 function. In family 2, compound heterozygous variants (c.1697C>T; p.(Ser566Phe)/c.1811C>T; p.(Thr604Met)) were found C-terminal to the motor domain, in agreement with a genotype-phenotype correlation. In vitro experiments performed on amnioblasts of one affected fetus from family 3 showed that primary cilia assembly was severely impaired, and that cytokinesis was also affected. In conclusion, our study describes novel forms of skeletal dysplasia associated with biallelic variants in KIF24. To our knowledge this is the first report implicating KIF24 variants as the cause of a skeletal dysplasia, thereby extending the genetic heterogeneity and the phenotypic spectrum of rare bone disorders and underscoring the wide range of monogenetic skeletal ciliopathies. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Copper sulfide nanostructures: synthesis and biological applications.

Over the past few years, considerable attention has been paid to biomedical applications of copper sulfide nanostructures owing to their enhanced physiochemical and pharmacokinetics characteristics in comparison to gold, silver, and carbon nanomaterials. The small-sized Cu x S y nanoparticles have the advantage to absorb efficiently in the near-infrared region (NIR) above 700 nm and the absorption can be tuned by altering their stoichiometries. Moreover, their easy removal through the kidneys overpowers the issue of toxicity caused by many inorganic substances. The low cost and selectivity further add to the advantages of Cu x S y nanostructures as electrode materials in comparison to relatively expensive materials such as silver and gold nanoparticles. This review is mainly focused on the synthesis and biomedical applications of Cu x S y nanostructures. The first part summarizes the various synthetic routes used to produce Cu x S y nanostructures with varying morphologies, while the second part targets the recent progress made in the application of small-sized Cu x S y nanostructures as biosensors, and their analysis and uses in the cure of cancer. Photoacoustic imaging and other cancer treatment applications are discussed. Research on Cu x S y nanostructures will continue to increase over the next few decades, and great opportunities lie ahead for potential biomedical applications of Cu x S y nanostructures.

Comparison of outcome of compression dressing for two days Vs seven days after varicose surgery.

Incompetence of the great saphenous vein (GSV) is a global issue and the most prevalent cause of chronic venous disease of the leg. Clinical manifestations range from moderate to severe, including tiredness, heaviness, and irritation, as well as hyperpigmentation and leg ulcers. A study was conducted to address this controversy,1 i.e. to determine the outcome of compression dressing after varicose vein surgery in terms of postoperative pain, on the Surgical floor, of Mayo Hospital, Lahore, from October 1, 2020, to April 1, 2021. A total of 60 patients with Primary varicose veins were enrolled in this study, fulfilling the inclusion criteria after obtaining approval from the ethical committee of the hospital. The patients were divided in two groups. Group A wore compression dressing for two days after surgery and Group B wore compression dressing for seven days after surgery. All the patients received 1gm Paracetamol I/V eight hourly followed by tablet Paracetamol 500mg P/O eight hourly. Then the outcome of compression dressing was analysed in the form of mean postoperative pain. The mean pain score was assessed on one week. Data were entered in SSPS v23.0. Stratification of pain score was done against age, gender, and grades of varicose veins. A comparison of the two groups was done by applying a t-test. A p-value of ≤ 0.05 was considered significant. Prescribing compression stockings for longer than two days after Trendelenburg's procedure leads to reduced pain and improved physical function during the first week after treatment.

Litchi chinensis inspired nanoformulations: a synergy guided approach for unraveling promising cytotoxic attributes of metal and nonmetal conjugates.

In present study, diverse Litchi chinensis-mediated nanostructures in combination with 5-fluorouracil drug were fabricated viz. Au, Se, Ag, Ag-Se, Ag-Au, 5-FU Ag-Se and 5-FU Ag-Au with subsequent characterization and scrutinization of their anticarcinogenic capabilities. UV-Visible spectroscopic analysis confirmed the state transition for each precursor salt. XRD and transmission electron microscopy analysis revealed spherical/quasispherical nanostructures with monoclinic crystalline organization ranged between 18 nm and 38 nm. FTIR analysis revealed fabricated nanoparticles to be capped with various phytoconstituents. DLS and Zeta potential analysis of unloaded and drug-loaded bielemental nanoparticles (BNPs) showed comparatively large hydrodynamic particle size distribution and sufficient stability of nanoparticles. BNPs showed promising lethality concentrations for brine shrimp (LC50 < 2 µg/ml) and antitumor (LC50 < 10 µg/ml) assessments. These findings were in positive correlation with the antioxidant inhibitory concentrations IC50 (74.2-180.1 µg/ml) of the tested entities. Ag-Se and Ag-Au were loaded with 5-FU (loading efficiency of 47% ± 1.14 and 25% ± 0.32, respectively) in light of their promising cytotoxic actions. All nanostructures showed profound hemocompatibility with maximum hemolytic activity as low as 2.4%. Highly significant difference (P < 0.01) was observed in antineoplastic potentials of unloaded and 5-FU loaded BNPs against HepG2 and HT144, with most substantial IC50 for 5-FU Ag-Au (8.95 ± 2.86 µg/ml). 5-FU Ag-Au was identified as a significant inducer of DNA fragmentation with maximum relative tail moment (HepG2: 3.45 ± 0.21) among all treatments.

RAB33B and PCNT variants in two Pakistani families with skeletal dysplasia and short stature.

BACKGROUND: Skeletal dysplasia is a heterogeneous group of disorders resulting from different genetic variants in humans. The current study was designed to identify the genetic causes of skeletal dysplasia and short stature in two consanguineous families from Pakistan, both comprised of multiple affected individuals. Patients in one family had proportionate short stature with reduced head circumference while affected individuals in the other family had disproportionate short stature. METHODS: Clinical data were obtained and radiological examinations of the index patients were completed. Whole genome sequencing for probands from both families were performed followed by Sanger sequencing to confirm segregation of identified variants in the respective families. In-silico pathogenicity score prediction for identified variant and amino acid conservation analysis was completed. RESULTS: Whole Genome Sequencing identified a known biallelic variant c.6176_6189delGTCAGCTGCCGAAG; p.(Gln2060ArgfsTer48) in PCNT gene and a novel biallelic variant c.174delC; p.(Asp60ThrfsTer7) in RAB33B gene respectively in affected members of the two families. Clinical imaging revealed platyspondyly and varus deformity in the legs of the affected members in the first family. Radiographs indicated severe platyspondyly, genu valgus deformity of legs and pectus carinatum for the patients in the second family. CONCLUSION: In this study we report the phenotypes and genetic variants in two unrelated families with two distinct forms of skeletal dysplasia. This study strengthens the previous findings that patients harboring PCNT variants are phenotypically homogeneous and also extends the genotypic spectrum of RAB33B variants.

Novel form of rhizomelic skeletal dysplasia associated with a homozygous variant in GNPNAT1.

BACKGROUND: Studies exploring molecular mechanisms underlying congenital skeletal disorders have revealed novel regulators of skeletal homeostasis and shown protein glycosylation to play an important role. OBJECTIVE: To identify the genetic cause of rhizomelic skeletal dysplasia in a consanguineous Pakistani family. METHODS: Clinical investigations were carried out for four affected individuals in the recruited family. Whole genome sequencing (WGS) was completed using DNA from two affected and two unaffected individuals from the family. Sequencing data were processed, filtered and analysed. In silico analyses were performed to predict the effects of the candidate variant on the protein structure and function. Small interfering RNAs (siRNAs) were used to study the effect of Gnpnat1 gene knockdown in primary rat chondrocytes. RESULTS: The patients presented with short stature due to extreme shortening of the proximal segments of the limbs. Radiographs of one individual showed hip dysplasia and severe platyspondyly. WGS data analyses identified a homozygous missense variant c.226G>A; p.(Glu76Lys) in GNPNAT1, segregating with the disease. Glucosamine 6-phosphate N-acetyltransferase, encoded by the highly conserved gene GNPNAT1, is one of the enzymes required for synthesis of uridine diphosphate N-acetylglucosamine, which participates in protein glycosylation. Knockdown of Gnpnat1 by siRNAs decreased cellular proliferation and expression of chondrocyte differentiation markers collagen type 2 and alkaline phosphatase, indicating that Gnpnat1 is important for growth plate chondrocyte proliferation and differentiation. CONCLUSIONS: This study describes a novel severe skeletal dysplasia associated with a biallelic, variant in GNPNAT1. Our data suggest that GNPNAT1 is important for growth plate chondrogenesis.