Fabrication of a Graphene@Ni foam-supported silver nanoplates-PANI 3D architecture electrode for enzyme-free glucose sensing.

Reliable and cost-effective glucose sensors are in rising demand among diabetes patients. The combination of metals and conducting polymers creates a robust electrocatalyst for glucose oxidation, offering enzyme-free, high stability, and sensitivity with outstanding electrochemical results. Herein, graphene is grown on nickel foam by chemical vapor deposition to make a graphene@nickel foam scaffold (G@NF), on which silver nanoplates-polyaniline (Ag-PANI) 3D architecture is developed by sonication-assisted co-electrodeposition. The resulting binder-free 3D Ag-PANI/G@NF electrode was highly porous, as characterized by XPS, FESEM, XRD, FTIR, and Raman spectroscopy. The binder-free 3D Ag-PANI/G@NF electrode exhibits remarkable electrochemical efficiency with a superior electrochemical active surface area. The amperometric analysis provides excellent anti-interference performance, a low limit of deduction (0.1 nM), robust sensitivity (1.7 x 1013 µA mM-1cm-2), and a good response time. Moreover, the Ag-PANI/G@NF enzyme-free sensor is utilized to observe glucose levels in human blood serums and exhibits excellent potential to become a reliable clinical glucose sensor.

Circulating tumor DNA and its role in detection, prognosis and therapeutics of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers; the most prominent is circulating tumor DNA (ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction (PCR) [emulsion PCR (ePCR), digital PCR (dPCR), and bead, emulsion, amplification, magnetic (BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection, treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations (either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1; 2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF; 3) DNA methylation (RASSF1A, SEPT9, KMT2C and CCNA2); 4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1; and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results. Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.

Evaluation of hypomagnesaemia in diabetic patients with nephropathy in a reference clinical laboratory: A comparative cross sectional study.

Serum Magnesium plays a significant role in different diabetic complications. This comparative cross sectional study was conducted to evaluate serum magnesium levels in patients with Type 2 Diabetes Mellitus (T2DM) with and without nephropathy. A total of 182 diabetic patients (91 with nephropathy and 91 without nephropathy) were included. Odds ratio were calculated and Mann Whitney U test was used to compare quantitative variables; p<0.05 was considered significant. The results showed that 64/91 (70.3%) patients with nephropathy had hypomagnesaemia as compared to 21/91 (23.07%) patients without nephropathy. The risk of hypomagnesaemia was higher in patients with nephropathy than without nephropathy (Odds ratio 2.7 vs 0.34). Median magnesium levels (1.73 mg/dl) were lower in patients with nephropathy as compared to patients without nephropathy (2.09 mg/dl), p<0.01. It is concluded that magnesium levels were significantly lower in patients with diabetic nephropathy as compared to without nephropathy.

Development and Characterization of Gentamicin-Loaded Arabinoxylan-Sodium Alginate Films as Antibacterial Wound Dressing.

Biopolymer-based antibacterial films are attractive materials for wound dressing application because they possess chemical, mechanical, exudate absorption, drug delivery, antibacterial, and biocompatible properties required to support wound healing. Herein, we fabricated and characterized films composed of arabinoxylan (AX) and sodium alginate (SA) loaded with gentamicin sulfate (GS) for application as a wound dressing. The FTIR, XRD, and thermal analyses show that AX, SA, and GS interacted through hydrogen bonding and were thermally stable. The AXSA film displays desirable wound dressing characteristics: transparency, uniform thickness, smooth surface morphology, tensile strength similar to human skin, mild water/exudate uptake capacity, water transmission rate suitable for wound dressing, and excellent cytocompatibility. In Franz diffusion release studies, >80% GS was released from AXSA films in two phases in 24 h following the Fickian diffusion mechanism. In disk diffusion assay, the AXSA films demonstrated excellent antibacterial effect against E.coli, S. aureus, and P. aeruginosa. Overall, the findings suggest that GS-loaded AXSA films hold potential for further development as antibacterial wound dressing material.

Pharmacological evaluation of anti-arthritic potential of terpinen-4-ol using in vitro and in vivo assays.

Terpinen 4-ol, a phytochemical is a monoterpene which has been reported for its anti-inflammatory effect. Present research was planned to check its effect against arthritis through in vitro and in vivo models. Terpinen 4-ol was evaluated through in-vitro procedures including blocking of protein (BSA and egg albumin) denaturation and human RBC membrane stabilization. In in vivo study, terpinen 4-ol (15, 30 and 60 mg/kg) was evaluated using formaldehyde and CFA arthritic models. Terpinen 4-ol significantly inhibited increase in paw and joint swelling as compared to diseased group. Terpinen 4-ol showed remarkable antioxidant effect (SOD, reducing power) and also improved body weight, haematological, histopathological and radiological parameters in CFA model. Also, moreover, the excess production of IL-1ß, TNF-α, IRAK, and NF-kB were noticeably attenuated in all terpinen 4-ol treated rats, however, IL-17 and IL-10 were distinctly increased compared to arthritic control rats in RT-PCR. Also, terpinen 4-ol showed promising antioxidant effect in DPPH assay. Henceforth, it might be concluded that terpinen 4-ol has anti-arthritic effect which can be attributed to the downregulation of pro-inflammatory cytokines.

Isatin derivatives as broad-spectrum antiviral agents: the current landscape.

In recent decades, several viruses have resulted in large outbreaks with serious health, economic and social consequences. The current unprecedented outbreak of the new coronavirus, SARS-COV-2, necessitates intensive efforts for delivering effective therapies to eradicate such a deadly virus. Isatin is an opulent heterocycle that has been proven to provide tremendous opportunities in the area of drug discovery. Over the last fifty years, suitably functionalized isatin has shown remarkable and broad-spectrum antiviral properties. The review herein is an attempt to compile all of the reported information about the antiviral activity of isatin derivatives with an emphasis on their structure-activity relationships (SARs) along with mechanistic and molecular modeling studies. In this regard, we are confident that the review will afford the scientific community a valuable platform to generate more potent and cost-effective antiviral therapies based on isatin templates.

A case of congenital methaemoglobinaemia with secondary polycythemia.

Haemoglobin contains iron in a ferrous form. When the iron is oxidized, it is called Methaemoglobin (MetHb). MetHb leads to tissue hypoxia, cyanosis, and secondary polycythemia. Methaemoglobinaemia is acquired or congenital. In this case, a 22-years-old male patient presented with cyanosis, headache, and lack of concentration. Cyanosis was present since birth. His previous investigations showed polycythemia. He was misdiagnosed on multiple occasions and was undergoing venesections for polycythemia. On evaluation at a private clinic, an Oxygen saturation gap was noted between the results of the pulse oximeter and arterial blood gas analyzer. This raised suspicion on the presence of MetHb. He was referred to Armed Forces Institute of Pathology, Rawalpindi for further workup.The sample obtained for MetHb was chocolate brown in colour. Analysis was done via co-oximetry. A high level of MetHb (45.6%) was obtained. All other radiological and haematological investigations were in the normal range. On the basis of history, clinical presentation, and investigations, he was diagnosed as a case of congenital methaemoglobinaemia with secondary polycythemia.

Pharmacological exploration of anti-arthritic potential of terbutaline through in-vitro and in-vivo experimental models.

Terbutaline have been reported to have anti-inflammatory activity. Present study aimed to check the anti-arthritic activity of terbutaline. The drug was tested using in vitro models (bovine serum albumin denaturation, egg albumin denaturation and HRBC membrane stabilization) and in vivo (formaldehyde induced arthritis). Results of bovine serum albumin denaturation assay illustrated that terbutaline inhibited 89.54±0.46% denaturation at 6400µg/ml concentration. Terbutaline resulted in dose dependent impediment of protein denaturation in egg albumin denaturation assay with 74.40±0.72% inhibition at concentration of 6400µg/ml. Terbutaline also showed protection of HRBC membrane against hypotonic stress in a dose dependent manner, with maximum 76.45±0.62% prevention at 6400µg/ml concentration. Results of formaldehyde induced arthritis model showed that paw volume was significantly declined by terbutaline with maximum percentage inhibition at 10th day of study period which implies immune inhibitory potential of terbutaline. Findings of present study concluded that terbutaline has arthritis reducing potential possible through inhibitory effects on synthesis and release of inflammatory mediators as well as limiting the formation of autoantigen. Thus, terbutaline might be the potential candidate for use in treatment of arthritis.

Development and evaluation of oral fast disintegrating film of ranitidine HCl by solvent casting method.

Here, we developed oral fast disintegrating film (ODF) of ranitidine hydrochloride (RHCl) by solvent casting method and assessed the impact of various formulation ingredients i.e. polymer concentration, type of plasticizers and superdisintegrants. Optimized film was developed with hydroxypropyl methyl cellulose (HPMC E5, 3% w/v) as film matrix, propylene glycol (PG) (10% w/w of polymer) as plasticizer and Pearlitol flash® (PF) (10% w/w of polymer) as release modifier. This film was chosen based on appearance, transparency, thickness, folding endurance and in vitro disintegration time (DT). Later on, optimized film was loaded with drug (50% w/w of polymer) (A12), which disintegrated within 15 seconds and released 81% of RHCl within two minutes. Furthermore, FTIR studies confirmed the absence of drug film ingredients interaction. SEM showed even distribution of RHCl and all excipients. Thus, A12 will be palatable for geriatric patients and helpful to avoid premature intestinal degradation.

Amino acid derivatives of 2-Mercaptobenzimidazoles suppress cytokines at the site of inflammation and block gastric H+/K+ ATPase.

Routinely used anti-inflammatory drugs are associated with off-target effects such as cyclooxygenase (COX)-1 inhibition and gastric ulcers. The aim of this study is to examine the anti-inflammatory potential and gastroprotective effects of synthetic amino acid derivatives of 2-mercaptobenzimidazole (MBAA1, MBAA2, MBAA3, MBAA4 and MBAA5). The results showed that compound MBAA5 possess a potential anti-inflammatory action by inhibition of 15-LOX and COX-2. MBAA5 also attenuated the pro-inflammatory cytokines and mediators (TNF-α, IL-1ß and COX-2) in rat hind paw in carrageenan-induced inflammatory model of rat. 2-mercaptobenzimidazole derivative, MBAA5 also inhibited gastric H+/K+ ATPase and demonstrated a better selectivity index for COX-2 (SI 27.17) in comparison to celecoxib (SI 41.43). Molecular docking studies predicted the binding interactions of the synthesized compounds with retrieved target proteins of H+/K+ ATPase, COX-1, COX-2, and 15-LOX. The results of in silico and molecular docking analysis of amino acid derivatives of 2-mercaptobenzimidazoles further explained their pharmacological activities. Moreover, these compounds presented better antimicrobial activity against three clinical isolates of Helicobacter pylori. Together, our findings suggested that these synthetic 2-mercaptobenzimidazole derivatives are safer therapeutic candidates for inflammation.

REVIEW- Covid-19: Diagnosis, summary of essays and evolving approaches.

COVID-19 spread worldwide after its outbreak in December 2019. This review paper aims to educate the readers regarding SARS-CoV-2 diagnostic and detection tools and the issues experienced by researchers. We identify on-the-horizon point-of-care diagnostic tests and inspire scholars to develop their innovations past conception. It will also effectively avoid potential pandemics to establish plug-and-play diagnostic information to handle the SARS infection. The authors agree that arbitrary-access, interconnected systems with flexible functionality accessible at the point-of-care, would enable fast and precise diagnosis and tracking.

Changes in Lifestyle, Health Practices, and Perceived Anxiety amidst the COVID-19 Pandemic: A Cross-Sectional Study Conducted on the General Population of Pakistan.

Background: The emergence of the coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges across the globe. In addition to its debilitating impacts on health, the pandemic has also resulted in sudden changes in the quality of life. Our study aims to assess and highlight the alterations in lifestyle, health practices, and perceived anxiety in amongst the Pakistani denizens during the categorical lockdown across the country. Methods: A cross-sectional study was conducted during April 2020 through an online self-administered questionnaire using the snowball sampling technique. The online survey included a diversified set of questions ranging from the demographics, participants' sleeping routine, physical activity, hygiene habits, daily routine, and dietary habits during the quarantine period. It also assessed their anxiety through a series of questions, stretching from their own apprehension of their mental health to their assumption regarding the uncertainty of the future. SPSS v23 was used for data analysis, and chi-square test was applied. Results: A total of 384 respondents were included in the study. The mean age of the participants was 21.26 ± 4.267 years. It was observed that 203 (52.9%) individuals spent most of their time in self-isolation on social media, and 167 (43.5%) of participants claimed to be undertaking online classes or watching television. Furthermore, half of the participants noted that their sleep duration had increased 194 (50.5%), along with increased levels of perceived anxiety 242 (63%). Conclusion: The imposed nationwide lockdown due to COVID-19 has extensively affected the daily routine of the people living in Pakistan, eliciting profound changes in their sleeping patterns, dietary habits, mental health, and physical activity. Therefore, addressing the issues that arise amidst the lockdown remains pivotal.

Potentially inappropriate medications use and its association with health-related quality of life among elderly cardiac patients.

BACKGROUND: Previous studies identified alarming use of potentially inappropriate medications (PIMs) in Pakistani population but its effect on health-related quality of life (HRQoL) is still largely unknown. OBJECTIVE: This study aimed to determine the association between PIMs use and HRQoL among elderly cardiac outpatients. METHOD: A descriptive, non-experimental, cross-sectional study was carried out from June 2018 to September 2018 in two outpatient departments of tertiary-care hospitals in the Punjab Province of Pakistan. The population under study were patients aged ≥ 65 years with at least one cardiovascular condition taking at ≥ 1 prescribed medication. Patients with PIMs were identified by using Beers criteria. HRQoL was assessed using EuroQoL-5 dimension (EQ-5D) and EuroQoL-visual analogue scale (EQ-VAS). The association of PIMs with HRQoL was analyzed using χ2 tests, independent sample t-test, and one-way ANOVA tests. Multiple linear regression analysis was used to determine how HRQoL varied by PIMs use after adjusting for patient-level covariates. RESULTS: Of 386 elderly cardiac patients, 260 (67.4%) patients were receiving at least one PIM. Mean EQ-5D scores were significantly lower among patients with PIMs (0.51) compared to patients without PIMs (0.65) (P < 0.001). In multiple linear regression analysis, increasing numbers of PIMs were significantly associated with lower EQ-5D scores [ß = - 0.040 (- 0.075, - 0.005), P < 0.001] and VAS scores [ß = - 1.686 (- 2.916, - 0.456), P < 0.05]. CONCLUSION: The present study concluded that exposure to PIM was significantly associated with lower HRQoL. This indicates that guidelines recommendations should be followed to improve patient's quality of life.

Emerging pharmacy services; Recommendations for emergency care of COVID-19 pandemic in low and middle-income countries.

The ongoing outbreak of coronavirus diseases (COVID-19) has been declared as Pandemic by the World Health Organization and now become a global health emergency. Low and Middle income-countries lack standard pharmacy services in terms of staff, education, training, pharmaceutical care, research, and practice. The literature aimed to provide emerging pharmacy services and recommend it to be implemented in low and middle-income countries. Currently, pharmacies were easily accessible sites by the community, a trained staff under the guidance of pharmacist can be helpful for the management of visiting customers. In the surge of disease, pharmacists proved themselves as a frontline defense for the community by significant contribution in identifying, reporting, and managing COVID-19 patients through pharmaceutical care services at the community level, hospital/clinical level, and through Tele-pharmaceutical services.

Nanoparticles incorporated hydrogels for delivery of antimicrobial agents: developments and trends.

The prevention and treatment of microbial infections is an imminent global public health concern due to the poor antimicrobial performance of the existing antimicrobial regime and rapidly emerging antibiotic resistance in pathogenic microbes. In order to overcome these problems and effectively control bacterial infections, various new treatment modalities have been identified. To attempt this, various micro- and macro-molecular antimicrobial agents that function by microbial membrane disruption have been developed with improved antimicrobial activity and lesser resistance. Antimicrobial nanoparticle-hydrogels systems comprising antimicrobial agents (antibiotics, biological extracts, and antimicrobial peptides) loaded nanoparticles or antimicrobial nanoparticles (metal or metal oxide) constitute an important class of biomaterials for the prevention and treatment of infections. Hydrogels that incorporate nanoparticles can offer an effective strategy for delivering antimicrobial agents (or nanoparticles) in a controlled, sustained, and targeted manner. In this review, we have described an overview of recent advancements in nanoparticle-hydrogel hybrid systems for antimicrobial agent delivery. Firstly, we have provided an overview of the nanoparticle hydrogel system and discussed various advantages of these systems in biomedical and pharmaceutical applications. Thereafter, different hybrid hydrogel systems encapsulating antibacterial metal/metal oxide nanoparticles, polymeric nanoparticles, antibiotics, biological extracts, and antimicrobial peptides for controlling infections have been reviewed in detail. Finally, the challenges and future prospects of nanoparticle-hydrogel systems have been discussed.

Diuretic and Anti-hyperuricemic Effects of Geranyl Acetate in Rats.

BACKGROUND: Geranyl acetate, a compound found in plant oils, has been studied for its potential effects on renal and cardiovascular ailments. OBJECTIVE: This study aimed to investigate the diuretic and anti-hyperuricemic properties of geranyl acetate in male Wistar rats using a hyperuricemia-induced rat model. METHODS: Molecular docking studies were conducted to assess geranyl acetate's interactions with various targets. in vitro studies were performed to evaluate its scavenging ability and inhibition of xanthine oxidase, urease, and acetylcholinesterase. Subsequently, we administered different doses of geranyl acetate (25, 50, and 100 mg/kg) and a reference drug (furosemide) to the rats to assess their acute and repeated dose diuretic effects over seven days. To understand the diuretic mechanism, we used inhibitors, such as L-- NAME, indomethacin, and atropine, prior to administering geranyl acetate. We also tested the anti-hyperuricemic potential of geranyl acetate on hyperuricemic rats. RESULTS: Molecular docking suggested strong binding between geranyl acetate and nitric oxide synthase. in vitro studies showed significant free radical scavenging activity and and inhibition of acetylcholinesterase, xanthine oxidase, and urease. The 100 mg/kg dose exhibited the most promising diuretic effects, with nitric oxide appearing to influence its action. Uric acid excretion increased at this dose, resembling allopurinol effects. CONCLUSION: Geranyl acetate has demonstrated significant diuretic and anti-hyperuricemic effects, likely influenced by nitric oxide release and inhibition of enzymes, like xanthine oxidase and urease. The findings have suggested potential benefits for individuals with kidney ailments, hypertension, and gout.

Laboratory Safety Climate Assessment and its Correlation with Safety Procedures Amongst Staff of a Reference Clinical Laboratory.

OBJECTIVE: To compare and correlate safety climate standards and safety practices among different subspecialities of pathology. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: The study was conducted at Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from February to November 2022. METHODOLOGY: Responses of 199 participants were recorded according to the validated Nordic Safety Climate Questionnaire (NOSACQ-50) and Lab Safety Survey form. The safety climate presented as seven dimensions according to the validated questionnaire was compared among different workgroups, based on subspeciality and job designation, using one-way ANOVA and independent sample t-test, respectively. Pearson's correlation was used to assess the relationship between the safety climate and safety practices. RESULTS: Among the safety climate dimensions, safety communication, trust in co-workers' safety competence (M=3.02) and workers trust in efficacy of safety systems (M=3.00) were the most positively perceived aspects followed by management's safety priority (M=2.98). Comparison of subspecialities showed significant differences in management safety empowerment, management safety justice, workers' safety commitment, safety communication, and trust in efficiency of safety systems (p<0.001 for all 5 factors). Chemical pathology workers and technical staff were workgroups with lower safety climate scores. A statistically significant positive correlation (r=0.97) was observed between the safety procedures and safety climate at an organisational level. CONCLUSION: The results demonstrated the existence of a good safety climate within the participating laboratories of the institute. It successfully identified areas that need further safety improvements. The study will help increase awareness about occupational safety and safety culture among healthcare workers in general and clinical laboratory setups in particular. KEY WORDS: Laboratory safety climate, Occupational health, Safe laboratory practices.

Discovery of Novel Tetramethylpyrazine Containing Chalcone Derivatives as Anti-Inflammatory Agents.

BACKGROUND: Chalcones are precursors of flavonoids and exhibit a broad spectrum of pharmacological activity. OBJECTIVE: As anti-inflammatory agents, two series of chalcone derivatives and chalcone-based oximes were synthesized and characterized. To integrate the tetramethylpyrazine moiety into these novel molecules, the multifunctional natural chemical ligustrazine was employed. METHODS: A variety of newly synthesized ligustrazine-based chalcones were utilized as precursors for the synthesis of new oximes and their inhibitory activity against COX-1, COX-2, and LOX-5 enzymes were compared. RESULTS: The conversion of ketones to their oxime derivatives increased the effectiveness of COX-1 and COX-2 inhibition. Due to the substituted ether groups, oxime derivative 5d had the lowest IC50 values of 0.027 ± 0.004 µM and 0.150 ± 0.027 µM for COX-1 and COX-2 isoenzymes, respectively. Notably, the oxime derivative's highest effectiveness is conferred by the presence of methoxymethoxy or hydroxy groups at the C-3 and C-4 positions on the phenyl ring. The 6b derivative with a long alkyl chain ether group was shown to be the most powerful 5-LOX inhibitor. All compounds were also assessed for their ability to inhibit nitric oxide generation and LPS-induced IL-6, IL-1ß, and TNF-α production in RAW 264.7 macrophages. Finally, in order to determine the structural effects responsible for the binding mechanism of compounds, they were docked into the binding sites of COX-1, COX-2, and 5-LOX, which revealed an inhibitory mechanism of action and demonstrated the relevance of various types of interactions. CONCLUSION: The findings showed that these novel compounds had a significant impact on antiinflammatory actions.

Emerging role of macrophages in non-infectious diseases: An update.

In the past three decades, a huge body of evidence through various research studies conducted on animal models, has demonstrated that the macrophages are centralized of all the leukocytes involved in diseases and, particularly, their role in non-infectious diseases has been studied extensively for which they have also been referred to as the "double-edged swords". The most versatile of all immunocytes, macrophages play a key role in health and diseases. Various experimental models have demonstrated the conventional paradigms such as the M1/M2 dichotomy, which is not as obvious and presents a complex characterization of the macrophages in the disease immunology. In human diseases, this M1-M2 continuum shows a complex web of mechanisms, which are majorly divided into the pro-inflammatory roles (derived mainly by the cytokines: IL-1, IL-6, IL-12, IL-23, and tumor necrosis factor) and anti-inflammatory roles (CCl-17, CCl-22, CCL-2, transforming growth factor (TGF), and interleukin-10), which are involved in the wound healing and pathogen-suppression. The conventional division of these macrophages as M1 and M2 is derived from the opposing functions of these macrophages; where M1 is involved in the tissue damage and pro-inflammatory roles and M2 promotes cell proliferation and the resolution of inflammation. Both these pathways down-regulate each other in diseases through a plethora of enzymatic and cytokine mediators.