Search

As most HIV rapid tests (HRT) detect only HIV‐1/2 antibodies, their performance during primary HIV infection is poor. Determine HIV Early detect (Abbott) (Determine) is the only HRT with an HIV‐1 p24‐antigen detection, but the impact of this addition in shortening the diagnostic window remains unclear. A total of 183 HIV‐1 primary infection samples were tested using the HRTs Determine and ONE STEP anti‐HIV (1&2) Test (InTec Products) (One‐Step). The pre‐seroconversion subgroup was defined as p24‐antigen positivity without Western blot nor Liaison XL (fouth generation enzyme immunoassay with distinct signal for p24‐antigen and HIV‐1 antibody) HIV‐1 antibodies. Global sensitivity (95% CI) was 95% (91–97) for Determine versus 80% (74%–85%) for One‐Step (difference p = 1.38e−06). Pre‐seroconversion subgroup sensitivity was lower, at 71.9 (54.6%‐84.4%) for Determine and 9.7% (3.3%–24.9%) for One‐Step. Among the 45 samples with an HIV‐1 infection date, no HRT was reactive up to 2 weeks. Between 2 and 3 weeks, Determine sensitivity was 78% (45%–95%) versus 56% (27%–81%) for One‐Step. From 3 weeks to 1 month Determine sensitivity was 90% (62%–98%) and One‐Step 45% (21%–72%). The last negative sample occurred at 3 weeks for Determine versus 70–90 days for One‐Step. HRT with p24‐antigen detection significantly shortens the diagnostic window from approximatively 3 months to 1 month. HRTs should be used with caution in the first month after HIV infection. [ABSTRACT FROM AUTHOR]

Thiocarbazones are widely used as bioactive and pharmaceutical intermediates in medicinal chemistry and have been shown to exhibit diverse biological and pharmacological activities such as antimicrobial, anticancer, anti-viral, anti-convulsant and anti-inflammatory etc. In continuation of our interest in biologically active heterocycles and in an attempt to synthesize a spiro derivative, 1,2,4,5-tetraazaspiro[5.7]tridecane-3-thione, herein, the synthesis of 1,5-dicyclooctyl thiocarbohydrazone (3) has been reported via reaction of the cyclooctanone and thiocarbohydrazide. The structure was assigned on the basis of detailed spectral analysis and also confirmed by X-ray crystal studies. The Hirshfeld surface analysis indicates that the most significant interaction is S⋯H (12.7%). The presentation of mechanistic aspects regarding the plausible route of its formation has also been included. The first hyperpolarizability (β0) was found to be 10.22 × 10−30 esu, which indicates that the compound exhibits good non-linear optical properties. The density functional theory (DFT) method has been used to characterize the spectroscopic properties and vibrational analysis of 1,5-dicyclooctyl thiocarbohydrazone (3) theoretically. The compound and cisplatin (standard) were screened for their antiproliferative activity against the human cervical cancer cell line (SiHa) and they exhibited significant activity with IC50 values of 250 μM and 15 μM, respectively. The inhibitory nature of the title compound against viral oncoprotein E6 was confirmed by studies using molecular docking analysis. The results of biological activity and in silico analysis indicate that the synthesized molecule could act as a precursor for the synthesis of new heterocyclic derivatives of medicinal importance. [ABSTRACT FROM AUTHOR]

Osteoporosis is a pressing global health issue, particularly among the elderly, as it involves the loss of bone mineral content (BMC) or bone mineral density (BMD) leading to weakened bones and an increased risk of fractures, affecting over 200 million people worldwide. The impact of this disease on quality of life and the risk of other medical complications is significant. Furthermore, the development in the treatment of osteoporosis has not made comparable progress with that for other musculoskeletal or chronic non-communicable diseases Alternative treatments, such as herbal medicine, have rather garnered attention in recent years due to their potential as effective therapeutic agents. Extensive research on chemical and pharmacological properties in cell-based and animal models has identified numerous medicinal plants and their compounds as having osteoprotective and anti-osteoporotic properties. These natural remedies present promising avenues for the development of therapeutic drugs. This review highlights the beneficial effect of promising phytochemicals for their osteoprotective effect and bone healing. [ABSTRACT FROM AUTHOR]

Background Vitamin D is an oil soluble vitamin responsible for various skeletal and non-skeletal functions, its deficiency is common in skin pathologies due to consequent abnormality in its synthesis and activation from skin cells. Objective The study targets to study the relationship between the degrees of vitamin D in psoriasis and acne patients, the research study compares the levels in patients suffering from the mentioned diseases. Methods The study employs a cross-sectional comparative method of analysis in Fauji Foundation Hospital Rawalpindi's Dermatology ward. 350 participants were selected by non-randomized convenient sampling, out of which 323 signed informed consent and qualified based on inclusion, and exclusion criteria were included. Out of these 323, 140 that were diagnosed with acne were included in group A based on inclusion criteria of age between 12 to 40. And, 183 participants diagnosed with psoriasis were included in group B based on inclusion criteria of age between 16 to 70. All these participants did not have a history of hypertension, diabetes mellitus, or renal and hepatic diseases, and were screened for normal RFTs and LFTs by taking blood samples. Blood samples were collected by using the technique of immune-enzyme assessment ((25(OH)-Vitamin D) with the enabling function of ELISA kit Immundiagnostik AG, Germany) that assessed the level of Vitamin D serum 25-hydroxycholecalciferol (25(OH) D). The result was analyzed on SPSS 26. Results Values of one paired t-test depicts that there is a huge difference between the mean Vitamin D measure of acne (M=41.47, SD=19.6) and Vitamin D level of psoriasis (M=21.83, SD=8.5). Regarding the correlation between the level of serums in acne and psoriasis patients. It was assessed that there has been a direct and non-negligible negative association between the degrees of Vitamin D serum in psoriasis and acne patients (r=0.13, p=0.05). It was also instigated that there had not been vital correlation in Vitamin D serum levels in patients suffering from acne (r=1, p=0.05). Conclusion The research study developed that a direct and significant relationship between the level of Vitamin D serum and psoriasis whereas no vital correlations were found between levels of Vitamin D serum and acne. [ABSTRACT FROM AUTHOR]

Background Alopecia areata (patchy alopecia) is an inflammatory disease which leads to hair loss over scalp and body. It is prevalent in 0.2% of the population without any racial or sexual predilection and may affect any age group and is prevalent in 25% of almost all alopecia cases.1 Azathioprine exerts its full effect after 4 to 6 weeks due to which most of our patients would leave treatment in initial phase of treatment. To cover up this issue of compliance and to increase its efficacy, we bridged this gap of 4 to 6 weeks with single shot of triamcinolone acetonide intramuscular injection. Although corticosteroids are effective in the treatment of alopecia areata whether administered intramuscularly, orally or intralesionally but since it is a chronic disorder and its long term use can lead to potential irreversible adverse effects, the need for steroid sparing immunosuppressive agents like azathioprine is recommended, which has favorable therapeutic action without many systemic side effects (success rate of 28.5 to 61%). Objective To investigate the efficacy of azathioprine with triamcinolone acetonide as a bridging therapy for the management of alopecia areata and its spectrum. Methods Two hundred patients with alopecia areata participated in an interventional single-arm pre and post-study at the Fauji Foundation Hospital in Rawalpindi from August 2018 to January 2021. After receiving consent, patients from dermatology OPD and inpatient settings were recruited. Patients were chosen using a non-probability consecutive sampling procedure. Results Calculation of the SALT score was done using the given formula as pretreatment and 8 weeks post treatment score. There is a 40.3% decrease in SALT score 12 weeks after treatment; the mean pre-treatment score was 35.65±3.7SD. 8 weeks after treatment, SALT score was 20.65±3.7SD and the difference between mean SALT score before and after treatment is statistically significant (t=34.3, p=<0.05). [ABSTRACT FROM AUTHOR]

In this study, we have investigated phytochemical classes, antileishmanial and cytotoxic activity of Fraxinus xanthoxyloides (Oleaceae) leaves. Powder of F. xanthoxyloides leaves was extracted with methanol to obtain the crude extract (FXM) and the resultant was fractionated with solvents in escalating polarity; n-hexane (FXH), chloroform (FXC), ethyl acetate (FXE), n-butanol (FXB) and the residual aqueous (FXA) fraction. Quantitative estimation of terpenoids, coumarins, flavonoids, phenolics and tannins was conducted. Anti-leishmanial activity was performed against Leishmania tropica promastigote stage parasite while insecticidal activity was assessed through brine shrimps lethality assay. Our results showed the maximum concentration of terpenoids in FXC while the highest quantity of coumarins, flavonoids, phenolics and tannins was recorded in FXE. Presence of terpenoids was not detected in FXB and in FXA. Among the extract/fractions, FXC exhibited the highest anti-leishmanial activity with LD50 of 15.23±0.9 µg/ml to that of glucantime (LD50 = 5.6±2.4 µg/ml) a reference drug. FXH exhibited the anti-leishmanial activity of LD50 = 40.68±1.9 µg/ml followed by FXE (LD50 = 102.9±3.1 µg/ml). Similarly potent insecticidal activity was recorded (LD50 = 28.15±1.8 µg/ml) for FXC followed by FXH (LD50 = 67.59±2.3 µg/ml). However, other fractions exhibited low level of anti-leishmanial and insecticidal activity. Correlation analysis exhibited a strong association (p < 0.05) between the terpenoids and the anti-leishmanial activity and a second but non significant association (p > 0.05) with the insecticidal activity. The coumarins established a medium association with the insecticidal activity. Other chemical classes exhibited a moderate to low level of association with the anti-leishmanial and the insecticidal activity. On the basis of these results we can conclude that chloroform fraction of F. xanthoxyloides is a potential source for anti-leishmanial and insecticidal activities and further studies are required to isolate the active constituents. [ABSTRACT FROM AUTHOR]

The cation/proton antiporter (CPA) family represents a class of transmembrane transporter proteins that play a crucial role in plants during high salinity stress by maintaining the cell's ionic balance and pH homeostasis. So far, the CPA genes have not been systematically characterized in tomato (Solanum lycopersicum). In this study, we identified and analyzed 33 putative CPA genes in tomato. Phylogenetic analysis showed that tomato CPAs could be classified into three subgroups, i.e., CHX (18 genes), KEA (8 genes), and NHX (7 genes). CPA genes within each subgroup shared similar motifs, conserved catalytic domains and gene structure. Further analysis revealed that the CPA genes were unevenly distributed on the chromosomes and segmental duplication events played a major role in the expansion of the CPA gene family in tomato. Gene expression analysis exhibited that CPA genes were differentially expressed in different tissues, various stages of fruit development, and differentially regulated in response to abiotic stresses, especially salt stress. Further, co-localization of tomato CPA genes with quantitative trait loci (QTL) of salt stress-related phenotypes revealed their broader functions in salt stress tolerance. Finally, predicted protein–protein interactions of tomato CPAs, gene ontology analysis, and the presence of putative cis-elements in the promoter further support the diverse role of tomato CPAs in plant development and plant stress tolerance. In brief, this study highlights the potential role of tomato CPAs in plant development and abiotic stress tolerance, especially in salt stress, and provides comprehensive information to explore new candidate genes for salt tolerance in tomato. [ABSTRACT FROM AUTHOR]

Fagonia indica is a rich source of pharmacologically active compounds. The variation in the metabolites of interest is one of the major issues in wild plants due to different environmental factors. The addition of chemical elicitors is one of the effective strategies to trigger the biosynthetic pathways for the release of a higher quantity of bioactive compounds. Therefore, this study was designed to investigate the effects of chemical elicitors, aluminum chloride (AlCl3) and cadmium chloride (CdCl2), on the biosynthesis of secondary metabolites, biomass, and the antioxidant system in callus cultures of F. indica. Among various treatments applied, AlCl3 (0.1 mM concentration) improved the highest in biomass accumulation (fresh weight (FW): 404.72 g/L) as compared to the control (FW: 269.85 g/L). The exposure of cultures to AlCl3 (0.01 mM) enhanced the accumulation of secondary metabolites, and the total phenolic contents (TPCs: 7.74 mg/g DW) and total flavonoid contents (TFCs: 1.07 mg/g DW) were higher than those of cultures exposed to CdCl2 (0.01 mM) with content levels (TPC: 5.60 and TFC: 0.97 mg/g) as compared to the control (TPC: 4.16 and TFC: 0.42 mg/g DW). Likewise, AlCl3 and CdCl2 also promoted the free radical scavenging activity (FRSA; 89.4% and 90%, respectively) at a concentration of 0.01 mM, as compared to the control (65.48%). For instance, the quantification of metabolites via high-performance liquid chromatography (HPLC) revealed an optimum production of myricetin (1.20 mg/g), apigenin (0.83 mg/g), isorhamnetin (0.70 mg/g), and kaempferol (0.64 mg/g). Cultures grown in the presence of AlCl3 triggered higher quantities of secondary metabolites than those grown in the presence of CdCl2 (0.79, 0.74, 0.57, and 0.67 mg/g). Moreover, AlCl3 at 0.1 mM enhanced the biosynthesis of superoxide dismutase (SOD: 0.08 nM/min/mg-FW) and peroxidase enzymes (POD: 2.37 nM/min/mg-FW), while CdCl2 resulted in an SOD activity up to 0.06 nM/min/mg-FW and POD: 2.72 nM/min/mg-FW. From these results, it is clear that AlCl3 is a better elicitor in terms of a higher and uniform productivity of biomass, secondary cell products, and antioxidant enzymes compared to CdCl2 and the control. It is possible to scale the current strategy to a bioreactor for a higher productivity of metabolites of interest for various pharmaceutical industries. [ABSTRACT FROM AUTHOR]

In current study, the effect of gibberellic acid was tested for production of biomass, polyphenolics and Steviol glycosides in adventitious root cultures of Stevia rebaudiana. Adventitious cultures were induced from the roots of in vitro grown plantlets on Murashige and Skoog (MS) medium containing combination of gibberellic acid (GA3; 0.5, 1.0, 1.5 and 2.0 mg/L) and naphthalene acetic acid (NAA; 0.5 mg/L). Initially, a known mass of inoculum roots were shifted into suspension media augmented with various GA3 concentrations. The growth behavior of adventitious roots was recorded every 3 days for a period of 30 days. Maximum biomass biosynthesis (13.12 g/flask) was noticed in exponential phase on 27th day in the suspension containing 2.0 mg/L of GA3. Other GA3 concentrations also displayed optimum patterns of biomass accumulation as compared to the control. Adventitious roots were investigated for total phenolic content (TPC) and production (TPP), total flavonoid content (TFC) and production (TFP), and 1, 1-diphenyl-2-picrylhydrazyl (DPPH)-based antioxidant potential. Maximum phenolics (TPC 9.84 mg gallic acid equivalent (GAE)/g-dry weight (DW)) and TPP (147.6 mg/L), TFC (5.12 mg Quercitin equivalent (QE)/g-DW) and TFP (76.91 mg/L) were observed in 2.0 mg/L GA3 treated cultures. The same concentration of gibberellic acid enhanced antioxidant activity (77.2%). Furthermore, maximum stevioside (7.13 mg/g-DW), rebaudioside-A (0.27 mg/g-DW) and dulcoside-A (0.001 mg/g-DW) were observed in roots exposed to 2.0 mg/L GA3. This is the first report on the application of GA3 on biomass accumulation and secondary metabolite production in S. rebaudiana. The current study will be helpful to scale up the adventitious root cultures in bioreactors for the production of biomass and pharmaceutically important secondary metabolites. [ABSTRACT FROM AUTHOR]

D614G genotype of SARS-CoV-2 virus is highly infectious and responsible for almost all infection for 2nd wave. However, there are currently no reports with D614G as vaccine candidate. Here we report the development of an mRNA-LNP vaccine with D614G variant and characterization in animal model. We have used special mRNA-architecture and formulation that provides suitable response of the product. The surface plasmon resonance (SPR) data with spike protein (S) revealed that immunization generated specific antibody pools against the whole extracellular domain (RBD and S2) of the spike protein. The anti-sera and purified IgGs from immunized mice neutralized SARS-CoV-2-pseudoviruses in ACE2-expressing HEK293 cells in a dose dependent manner. Importantly, single-dose immunization protected mice-lungs from homotypic-pseudovirus entry and cytopathy. The immunologic responses have been implicated by a balanced and stable population of CD4+ cells with a Th1 bias. The data suggested great promise for immediate translation of the technology to the clinic. [ABSTRACT FROM AUTHOR]

Cancer is a disease in which repeated rounds of mutations cause uncontrolled growth of cells, which prospers at the expense of their neighbor cells and then eventually leads to the destruction of the whole cellular community. Chemopreventive drugs either prevent DNA damage, which results in malignancy, or they stop or reverse the division of premalignant cells with DNA damage, which inhibits the growth of cancer. There is an obvious need for an alternate strategy given the ongoing rise in cancer incidence, the ineffectiveness of traditional chemotherapies to control cancer, and the excessive toxicity of chemotherapies. From antiquity to date, the saga of the usage of plants as medicine has been the mainstay among people worldwide. In recent years, extensive studies have been conducted on medicinal plants, spices, and nutraceuticals, as these have gained much popularity in reducing the risk of several cancer types in humans. Extensive studies on cell culture systems and animal models have demonstrated that various medicinal plants and nutraceuticals from various natural resources and their products, such as major polyphenolic constituents, flavones, flavonoids, antioxidants, etc, provide considerable protection against many cancer types. As shown in the literatures, the major aim of studies conducted is to develop preventive/therapeutic agents which can induce apoptosis in cancer cells without affecting normal cells. Projects are going on worldwide to find better ways to eradicate the disease. The study of phytomedicines has shed new light on this topic as research to date has proven that they have antiproliferative and apoptotic capabilities that will aid in the development of novel cancer prevention options. Dietary substances, such as Baicalein, Fisetin, and Biochanin A have shown that they have an inhibitory effect on cancer cells, suggesting that they may work as chemopreventive agents. This review discusses the chemopreventive and anticancer mechanisms of such reported natural compounds., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)