Smart Technologies used as Smart Tools in the Management of Cardiovascular Disease and their Future Perspective.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. The advent of smart technologies has significantly impacted the management of CVD, offering innovative tools and solutions to improve patient outcomes. Smart technologies have revolutionized and transformed the management of CVD, providing innovative tools to improve patient care, enhance diagnostics, and enable more personalized treatment approaches. These smart tools encompass a wide range of technologies, including wearable devices, mobile applications,3D printing technologies, artificial intelligence (AI), remote monitoring systems, and electronic health records (EHR). They offer numerous advantages, such as real-time monitoring, early detection of abnormalities, remote patient management, and data-driven decision-making. However, they also come with certain limitations and challenges, including data privacy concerns, technical issues, and the need for regulatory frameworks. In this review, despite these challenges, the future of smart technologies in CVD management looks promising, with advancements in AI algorithms, telemedicine platforms, and bio fabrication techniques opening new possibilities for personalized and efficient care. In this article, we also explore the role of smart technologies in CVD management, their advantages and disadvantages, limitations, current applications, and their smart future.

Inter-ethnic genetic variations and novel variant identification in the partial sequences of CYP2B6 gene in Pakistani population.

BACKGROUND: Some single nucleotide polymorphisms (SNPs) in the cytochrome P450 (CYP)2B6 gene lead to decreased enzyme activity and have an impact on drug metabolism. The present study was designed to investigate the patterns of genetic distinction across a hypervariable region of the CYP2B6 gene, known to contain important SNPs, i.e. rs4803419 and rs3745274, among five major ethnic groups of the Pakistani population. METHODS: Arlequin v3.5.DnaSPv6.12. and network 5 resources were used to analyze population genetic variance in the partial CYP2B6 gene sequences obtained from 104 human samples belonging to Punjabi, Pathan, Sindhi, Seraiki and Baloch ethnicities of Pakistan. The partial CYP2B6 gene region analyzed in the current study is previously known to possess important SNPs. RESULTS: The data analyses revealed that genetic variance among samples mainly came from differentiation within the ethnic groups. However, significant genetic variation was also found among the various ethnic groups. The high pairwise Fst genetic distinction was observed between Seraiki and Sindhi ethnic groups (Fst = 0.13392, P-value = 0.026) as well as between Seraiki and Balochi groups (Fst = 0.04303, P-value = -0.0030). However, the degree of genetic distinction was low between Pathan and Punjabi ethnic groups. Some SNPs, including rs3745274 and rs4803419, which are previously shown in strong association with increased plasma Efavirenz level, were found in high frequency. Besides, a novel SNP, which was not found in dbSNP and Ensemble databases, was identified in the Balochi ethnicity. This novel SNP is predicted to affect the CYP2B6 splicing pattern. CONCLUSION: These results may have significant implications in Pakistani ethnicities in the context of drugs metabolized by CYP2B6, especially in Seraiki and Balochi ethnicity. The novel heterogeneous SNP, found in the present study, might lead to altered drug-metabolizing potential of CYP2B6 and, therefore, may be implicated in non-responder phenomenon.

Novel Insight into Potential Leishmanicidal Activities of Transdermal Patches of Nigella Sativa: Formulation Development, Physical Characterizations, and In vitro/In vivo Assays.

Cutaneous Leishmaniasis (CL) is the most common type of Leishmaniasis, which annually affects 1.5 million people worldwide. About 90% of cases are reported from countries such as Iran, Afghanistan, Pakistan, Iraq, and Saudi Arabia. The purpose of the present study was to fabricate transdermal patches of Nigella sativa (NS), characterize, and to check its in vitro/in vivo anti-Lieshmanial activity. Hydroalcoholic extract was analyzed for preliminary phytochemicals. Five formulations of transdermal patches (NS1, NS2, NS3, NS4, and NS5) were prepared by solvent evaporation method. The optimized formulation NS5 was characterized for Fourier transform-infrared spectroscopy (FTIR), smoothness, brittleness, clarity, thickness, folding endurance, uniformity of weight, percent moisture content, in vitro drug release, release kinetics, ex vivo drug permeation, and in vitro anti-Lieshmanial activity. In vivo anti-Lieshmanial activity was assessed in 30 patients (n = 30) suffering from CL. The FTIR studies showed no incompatibility among the active extract and polymers. In vitro anti-Lieshmanial assay was 194.6% ± 1.88% as compared with standard drug (p > 0.05) and in vivo anti-Lieshmanial activity was 75%. The drug release after 24 h was 87.0% ± 0.94% in NS5, which showed non-Fickian diffusion mechanism while drug permeation across rabbit skin after 24 h was up to 80.0% ± 0.91%. The results concluded that problems related to the parenteral medications used for Lieshmanial treatment can be managed by applying extract of NS seeds in the form of transdermal patch.

Toxicological Evaluation of Novel Cyclohexenone Derivative in an Animal Model through Histopathological and Biochemical Techniques.

Toxicity studies were conducted to provide safety data of potential drug candidates by determining lethal and toxic doses. This study was designed for pre-clinical evaluation of novel cyclohexenone derivative with respect to the acute and sub-acute toxicity along with the diabetogenic potential. Acute and sub-acute toxicity were assessed after intraperitoneal (i.p) injection of the investigational compound through selected doses for 21 days. This was followed by assessment of isolated body organs (liver, kidney, heart and pancreas) via biochemical indicators and histopathological techniques. No signs of toxicity were revealed in the study of acute toxicity. Similarly, a sub-acute toxicity study showed no significant difference in biochemical indicators on 11th and 21st days between treated and control groups. However, in blood urea nitrogen (BUN) and random blood glucose/sugar (RBS) values, significant differences were recorded. Histopathological evaluation of liver, kidney, pancreas and heart tissues revealed mild to severe changes in the form of steatosis, inflammation, fibrosis, necrosis and myofibrillary damages on 11th and 21st days of treatment. In conclusion, the median lethal dose of the tested compound was expected to be greater than 500 mg/kg. No significant change occurred in selected biomarkers, except BUN and RBS levels, but a histopathological study showed moderate toxic effect on liver, kidney, pancreas and heart tissues by the cyclohexenone derivative.

Antihyaluronidase and Alkaline Phosphatase (ALP) Activities of Medicinal Plants to Combat Echis carinatus Venom-Induced Toxicities.

Snakebite is one of the most neglected diseases of developing countries. Deaths due to snakebite envenoming are quite high in Pakistan, and many deaths are caused by Echis carinatus envenomation. Traditional use of medicinal plants against snakebites is a common practice in Pakistan due to countless benefits. The current study was performed with the objective to evaluate eighteen Pakistani medicinal plants inhibitory potential against hyaluronidase and alkaline phosphatase enzymes of Pakistani Echis carinatus venom. Hyaluronidase activity (0.2-1.6 mg/0.1 mL) and alkaline phosphatase activity (0.1-0.8 mg/0.1 mL) were measured in dose-dependent manner. Crude methanolic extracts of medicinal plants were used for in vitro investigation of their inhibitory activity against toxic enzymes. All active plants were fractioned using different solvents and were again analyzed for inhibitory activity of same enzymes. Results indicated all plants were able to neutralize hyaluronidase that Swertia chirayita (Roxb. ex Flem.) Karst., Terminalia arjuna Wight and Arn, Rubia cordifolia Thumb., and Matthiola incana (L.) R.Br. inhibited maximum hyaluronidase activity equivalent to standard reference (p > 0.5). Pakistani medicinal plants are dense with natural neutralizing metabolites and other active phytochemicals which could inhibit hyaluronidase activity of Pakistani Echis carinatus venom. Further advanced studies at molecular level could lead us to an alternative for envenoming of Pakistani Echis carinatus venom.

Reduced sarcoplasmic reticulum Ca2+ ATPase activity underlies skeletal muscle wasting in asthma.

AIMS: Skeletal muscle mass and strength are reduced in asthma and contribute to compromised functional capacity in asthmatic patients. However, an effective pharmacological intervention remains elusive, partly because molecular mechanisms dictating muscle decline in asthma are not known. MATERIALS: We investigated the potential contribution(s) of skeletal muscle sarcoplasmic reticulum Ca2+ ATPase (SERCA) to muscle atrophy and weakness in asthmatic patients. Quadriceps muscle biopsies were taken from 58 to 72 years old male patients with mild and advanced asthma and the SERCA activity was analyzed in association with cellular redox environment and myonuclear domain (MND) size. KEY FINDINGS: Maximal SERCA activity was reduced in skeletal muscles of mild and advanced asthmatics and was associated with reduced expression of SERCA2 protein and upregulation of sarcolipin, a SERCA inhibitory lipoprotein. We also found downregulation of Ca2+ release protein calstabin and upregulation of Ca2+ buffer, calsequestrin in skeletal muscles of asthmatic patients. The atrophic single muscle fibers had smaller cytoplasmic domains per myonucleus possibly indicating the reduced transcriptional reserves of individual myonuclei. Plasma periostin and CAF22 levels were significantly elevated in asthmatic patients and showed a strong correlation with hand-grip strength. These changes were accompanied by substantially elevated markers of global oxidative stress including lipid peroxidation and mitochondrial ROS production. CONCLUSION: Taken together, our data suggest that muscle weakness and atrophy in asthma is in part driven by SERCA dysfunction and oxidative stress. The data propose SERCA dysfunction as a therapeutic intervention to address muscle decline in asthma.

Anti-5'-Nucleotidases (5'-ND) and Acetylcholinesterase (AChE) Activities of Medicinal Plants to Combat Echis carinatus Venom-Induced Toxicities.

Echis carinatus is one of the highly venomous snakes of Pakistan that is responsible for numerous cases of envenomation and deaths. In Pakistan, medicinal plants are commonly used traditionally for snakebite treatment because of their low cost and easy availability in comparison with antivenom. The current research is aimed at evaluating the inhibitory activity of Pakistani medicinal plants against acetylcholinesterase and 5'-nucleotidases present in Echis carinatus venom. Acetylcholinesterase and 5'-nucleotidase enzymatic assays were performed at different venom concentrations to check the activity of these enzymes. Methanolic extracts from different parts of plants were used for in vitro determination of their inhibitory activity against 5'-nucleotidases in snake venom. Active methanolic extracts were subsequently fractioned using different solvents, and these fractions were also assessed for their anti-5'-nucleotidase activity. Results of this study exhibited that Eugenia jambolana Willd. ex O. Berg, Rubia cordifolia L., Trichodesma indicum (L.) R. Br., Calotropis procera (Wild.) R. Br., Curcuma longa L., and Fagonia arabica L. were able to significantly (p > 0.5) neutralize the 5'-nucleotidase activity by 88%, 86%, 86%, 85%, 83.7%, and 83%, respectively, compared with a standard antidote (snake venom antiserum). Thus, this study indicates that these plants possess the potential to neutralize one of the toxic enzymatic components of Echis carinatus venom and hence can help to augment the future efforts of developing alternative therapy for the management of snakebites.

In-vitro and in-silico anticancer potential of taxoids from Taxus wallichiana Zucc.

INTRODUCTION: Natural products derived from medicinal plants provide beneficial cancer chemotherapeutic drugs. Bioactive constituents from plants are explored for their anticancer properties. METHODS: Three known compounds (deacetylbaccatin III, tasumatrol B, and taxawallin J) were isolated from Taxus wallichiana. Compounds were screened against four cancer cell lines, such as eA498, HepG2, NCI-H226, and MDR 2780AD. Cytotoxic activity was evaluated using MTT assay against cancer cell lines. RESULTS: Tasumatrol B showed good cytotoxic activity conducted for the improvement of inhibiting potential of these compounds against the cancer drug target protein (EGFR tyrosine kinase enzyme). The docking study showed that all compounds have binding affinities and interaction profile with the receptor tyrosine kinase. DISCUSSION: The study suggests that these compounds could be used for the discovery of novel inhibitors against the target receptors for the treatment of cancer.

Robust Synthesis of Ciprofloxacin-Capped Metallic Nanoparticles and Their Urease Inhibitory Assay.

The fluoroquinolone antibacterial drug ciprofloxacin (cip) has been used to cap metallic (silver and gold) nanoparticles by a robust one pot synthetic method under optimized conditions, using NaBH4 as a mild reducing agent. Metallic nanoparticles (MNPs) showed constancy against variations in pH, table salt (NaCl) solution, and heat. Capping with metal ions (Ag/Au-cip) has significant implications for the solubility, pharmacokinetics and bioavailability of fluoroquinolone molecules. The metallic nanoparticles were characterized by several techniques such as ultraviolet visible spectroscopy (UV), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) methods. The nanoparticles synthesized using silver and gold were subjected to energy dispersive X-ray tests in order to show their metallic composition. The NH moiety of the piperazine group capped the Ag/Au surfaces, as revealed by spectroscopic studies. The synthesized nanoparticles were also assessed for urease inhibition potential. Fascinatingly, both Ag-cip and Au-cip NPs exhibited significant urease enzyme inhibitory potential, with IC50 = 1.181 ± 0.02 µg/mL and 52.55 ± 2.3 µg/mL, compared to ciprofloxacin (IC50 = 82.95 ± 1.62 µg/mL). MNPs also exhibited significant antibacterial activity against selected bacterial strains.

Efficient PPA-SiO2-catalyzed synthesis of ß-enaminones under solvent-free conditions.

An efficient method has been developed for the synthesis of ß-enaminones under solvent-free reaction conditions using PPA-SiO2 as catalyst. The reaction yields were good to excellent (up to 90%). This methodology affords high selectivity and good tolerance of a variety of different functional groups present on both aromatic and aliphatic amines. In addition, the methodology is environmentally benign and cost-effective due to absence of solvent and easy work-up.

Antinociceptive activity of cyclopeptide alkaloids isolated from Ziziphus oxyphylla Edgew (Rhamnaceae).

The current study was designed to evaluate the antinociceptive profile of five cyclopeptide alkaloids isolated from Ziziphus oxyphylla, including Oxyphylline-B 1, Oxyphylline C 2 Oxyphylline-D 3, Nummularin-C 4, and Nummularin-R 5. The effect was studied in acetic acid induced writhing and formalin induced flinching behavior tests, at 2.5 and 5mg/kg i.p. In the post-acetic acid induced writhing test, the compounds significantly ameliorated abdominal constrictions in a dose dependent manner, with compounds 1 and 5 showing 80.98% and 77.87% protection, respectively. When challenged in the formalin induced test, pretreatment of compounds significantly attenuated painful sensation in both phases. Moreover, compounds 1 and 5 were more effective with 45.32% and 75.32% for 1 and 36.77% and 71.10% protection for 5, in the 1st and 2nd phases respectively. The peripheral analgesia was strongly augmented by the central effects of these compounds. The current finding strongly supports the ethnomedicinal use of this valuable medicinal plant in various painful conditions.

Evaluation of anti-inflammatory activity of selected legumes from Pakistan: in vitro inhibition of cyclooxygenase-2.

Crude methanolic extracts of selected legumes namely, black gram (Vigna mungo L.), green gram (Vigna radiata (L.) R. Wilczek ), soybean (Glycine max (L.) Merr.) and lentil (Lens culinaris Medik.) were investigated for anti-inflammatory effects, using COX-2 producing PGE(2) inhibitory assay. Percentage inhibition observed was 73.93, 79.84, 92.17 and 74.47 for black gram, green gram, soybean and lentil respectively at 20µg/ml extract concentration. The 100µg/ml concentration showed increase in the percent inhibition except for soybean. This is the first report on COX-2 inhibitory potential of food legumes.

New 14-membered cyclopeptide alkaloids from Zizyphus oxyphylla Edgew.

Two new 14-membered cyclopeptide alkaloids, Oxyphylline B (4) and Oxyphylline C (5), along with three known 13-membered cyclopeptide alkaloids, were isolated from stem and roots of Zizyphus oxyphylla Edgew. The compounds were tested for antibacterial activity. Oxyphylline B (4) showed comparatively better antibacterial activities against Escherichia coli (MIC, 5 µg/mL) than other compounds. This compound also exhibited weak antimicrobial activities against Staphylococcus aureus (MIC, 25 µg/mL), Pseudomonas aeruginosa (MIC, 50 µg/mL) and Salmonella typhi (MIC, 50 µg/mL).

Report: Platelet aggregation inhibition activity of selected legumes of Pakistan.

The current study was designed to explore the platelet aggregation activity of methanolic extracts of green gram, lentil, mash bean and soya bean. The extracts dose-dependently inhibited platelet aggregation initiated by arachidonic acid (AA) and platelet activating factor (PAF). Extract of green gram was effective only against AA mediated activity while mash bean and soya bean extracts were effective against both AA and PAF mediated activity. But lentil extract has no activity. The order of activity based on IC(50) value is, Mash bean > Soya bean > Green gram. This preliminary result suggests that legume seed extract may be taken as a candidate lead natural compound to be considered in the search for natural products with beneficial effects on aberrant platelet activation mediated cardiovascular disorders.

Platelet aggregation and anti-inflammatory effects of garden pea, Desi chickpea and Kabuli chickpea.

Inflammation is the natural body defense mechanism for the removal of injurious agents, necrosed cells and tissues from the body. This study was aimed to evaluate the anti-inflammatory and platelet aggregation effects of three medicinal plants of Pakistan. Methanolic extract of garden pea inhibited arachidonic acid (AA)-induced platelet aggregation (IC50 = 35 microg/mL) and platelet activating factor (PAF)-induced platelet aggregation (IC50 = 38 microg/mL) in a dose dependent fashion. Methanolic extract of Desi chickpea inhibited arachidonic acid (AA) induced platelet aggregation (IC50 value = AA = 46 microg/mL) in dose dependent fashion while was found not active against PAF-induced platelet aggregation. Methanolic extract of Kabuli chickpea was found not active against both arachidonic acid (AA)-induced platelet aggregation and PAF-induced platelet aggregation. The best potential to inhibit in vitro COX-2 activity showed garden pea (Pisum sativum: the synthesis of PGE2 reduced by 92% in comparison with untreated control wells) followed by Desi chickpea (Cicer arietinum var; 87% inhibition) and Kabuli chickpea extracts (Cicer arietinum var: 65% inhibition). All extracts were tested at concentration 20 microg/mL. in COX-2 assay. The results indicate that if the same were happening in vito, Garden pea, Desi chickpea and Kabuli chickpea could be useful as natural antithrombotic anti-inflammatory materials.

Analgesic and antiinflammatory activities of taxoids from Taxus wallichiana Zucc.

A study was conducted to identify constituents that might be responsible for analgesic and antiinflammatory conditions. Tasumatrol B, 1,13-diacetyl-10-deacetylbaccatin III (10-DAD) and 4-deacetylbaccatin III (4-DAB) were isolated from the bark extract of Taxus wallichiana Zucc. All the compounds were assessed for analgesic and antiinflammatory activities using an acetic acid-induced writhing model, a hot-plate test, a carrageenan-induced paw oedema model, a cotton-pellet oedema model and in vitro lipoxygenase inhibitory assay. All the compounds, especially tasumatrol B, revealed significant analgesic activity in comparison to a saline group based on an acetic acid-induced model. Similarly all of the test compounds, particularly tasumatrol B, showed significant antiinflammatory activity. However, all the compounds failed to exhibit any considerable activity in of the hot-plate test and the in vitro lipoxygenase inhibitory assay. This study has highlighted the potential of tasumatrol B to be further explored as a new lead compound for the management of pain and inflammation, one that has been discovered by scientific validation of the traditional medicinal use of T. wallichiana Zucc.

Biological screening of selected flora of Pakistan.

Methanolic extracts of different parts of five medicinal plants, Ferula assafoetidaL. resin, Grewia asiaticaL. leaves, Ipomoea hederaceaJacq. seeds, Lepidium sativumL. seeds and Terminalia chebulaRetz. fruits were tested in vitrofor their cytotoxic, phytotoxic, insecticidal, nematicidal and anthelmintic activities. Ipomoea hederaceashowed very significant phytotoxic and cytotoxic activity, with 100% inhibition of Lemna minorgrowth and 100% death of Artemia salinaat concentrations of 1000 and 100 µg mL-1. Grewia asiaticaexhibited very weak activities while Lepidium sativumand Ferula assafoetidashowed moderate to good potential in all three bioassays. The results suggest screening of Ipomoea hederaceaseeds further for isolation of bioactive compounds that may be responsible for its toxic potential.

Biological screening of selected flora of Pakistan

Methanolic extracts of different parts of five medicinal plants, Ferula assafoetidaL. resin, Grewia asiaticaL. leaves, Ipomoea hederaceaJacq. seeds, Lepidium sativumL. seeds and Terminalia chebulaRetz. fruits were tested in vitrofor their cytotoxic, phytotoxic, insecticidal, nematicidal and anthelmintic activities. Ipomoea hederaceashowed very significant phytotoxic and cytotoxic activity, with 100% inhibition of Lemna minorgrowth and 100% death of Artemia salinaat concentrations of 1000 and 100 µg mL-1. Grewia asiaticaexhibited very weak activities while Lepidium sativumand Ferula assafoetidashowed moderate to good potential in all three bioassays. The results suggest screening of Ipomoea hederaceaseeds further for isolation of bioactive compounds that may be responsible for its toxic potential.

4-({[(E)-Pyridin-3-yl-methyl-idene]amino}-meth-yl)cyclo-hexa-necarb-oxy-lic acid.

The title compound, C(14)H(18)N(2)O(2), contains two geometrically different mol-ecules in the asymmetric unit: the basal plane of the cyclo-hexane chair and the N-[pyridin-3-yl-methyl-idene]methanamine moiety are oriented at dihedral angles of 71.77 (7)° and 83.42 (8)°. In the crystal, the mol-ecules are linked by O-H⋯N hydrogen bonds, generating C(13) head-to-tail chains extending along the base vector [103]. R(2) (2)(26) ring motifs are formed due to the C-H⋯·O inter-actions that link neighbouring chains. There also exist π-π inter-actions [centroid-centroid separation = 3.6925 (12) Å] between the symmetry-related pyridine rings of one of the independent mol-ecules.

Anti-inflammatory activities of Taxusabietane A isolated from Taxus wallichiana Zucc.

Current study was conducted to identify constituents of Taxus wallichiana Zucc. that might be responsible for its folk use in anti-inflammatory conditions. Taxusabietane A was isolated from the bark extract of Taxus wallichiana Zucc. Taxusabietane A was analyzed for in-vitro and in-vivo anti-inflammatory activities using Lipoxygenase (LOX) inhibition assay and carrageenan-induced paw edema model. Taxusabietane A revealed considerable LOX inhibitory activity with the IC(50) value being 57 ± 0.31. Standard compound Baicalein showed the IC(50) value being 22.1 ± 0.03 µM. Taxusabietane A also showed significant (5 and 10 mg/kg) anti-inflammatory activity induced by carrageenan. However, this study highlighted the potential of Taxusabietane A to be further explored as a new lead compound for management of conditions associated with inflammation.