Efficacy and mechanism of Jasminum sambac gel for musculoskeletal injuries.

OBJECTIVE: Formulate a gel and test its scientific efficacy for treating musculoskeletal ailments with or without phonophoresis. METHODS: Gel was made from Jasminum sambac leaf extract (30:70 aqueous-methanolic). A pragmatic, community-based, double-blinded randomized clinical study (IRCT20230202057310N1) was undertaken on 380 pre-diagnosed individuals with 1st and 2nd-grade musculoskeletal injuries, divided into four parallel groups (n = 95 per group): Group I got phonophoresis-applied J. sambac 10% gel. Group II got phonophoresis-applied diclofenac diethylammonium 2% gel. J. sambac 10% gel was superficially massaged onto Group III. Group IV received a superficial massage with diclofenac diethylammonium 2% gel. Color, stability, pH, spreadability, beginning of pain relief, discomfort, stiffness, and activities of daily living were recorded using the Numeric Pain Rating Scale (NPRS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) Scale. Methods included phytochemical analysis, molecular docking, and antioxidant quantification using 2,2-diphenylpicrylhydrazyl (DPPH), nitric oxide (NO), and superoxide dismutase (SOD) tests. RESULTS: J. sambac gel worked better than diclofenac gel in phonophoresis and massage, with regard to NPRS P<0.001, WOMAC pain P<0.001, WOMAC stiffness P<0.003, and WOMAC activities of daily living (ADLs) P<0.001. There were also significant differences in pain, stiffness, and ADLs. J. sambac showed significant (P<0.005-0.001) results. CONCLUSION: J. sambac gel relieved pain and inflammation in musculoskeletal injury patients. J. sambac gel is natural, cheap, and easy to make. Better drug absorption may explain the effectiveness of phonophoresis.

Effect of different concentrations of resveratrol on nuclear maturation and in-vitro development competence of oocytes of Nili Ravi buffalo.

Buffaloes are considered animals of the future with the ability to survive under unfavorable conditions. However, the lack of access to superior germplasm poses a significant challenge to increasing buffalo production. Resveratrol has been shown to improve oocyte quality and developmental competence in various animals during in vitro embryo development. However, limited information is available on the use of resveratrol to improve the in vitro maturation and development competence of Nili Ravi buffalo oocytes. Therefore, the current study aimed to investigate the influence of different concentrations of resveratrol on the maturation, fertilization, and development of buffalo oocytes under in vitro conditions. Oocytes were collected from ovaries and subjected to in vitro maturation (IVM) using varying concentrations of resveratrol (0 µM, 0.5 µM, 1 µM, 1.5 µM, and 2 µM), and the maturation process was assessed using a fluorescent staining technique. Results indicated no significant differences in oocyte maturation, morula rate, and blastocyst rate among the various resveratrol concentrations. However, the cleavage rate notably increased with 1 µM and 1.5 µM concentrations of resveratrol (p < 0.05). In conclusion, the study suggests that adding 1 µM of resveratrol into the maturation media may enhance the cleavage and blastocyst hatching of oocytes of Nili Ravi buffaloes. These findings hold promise for advancing buffalo genetics, reproductive performance, and overall productivity, offering potential benefits to the dairy industry, especially in Asian countries.

Phytochemical, antioxidant, antipyretic and anti-inflammatory activities of aqueous-methanolic leaf extract of Mangifera indica.

OBJECTIVE: Plant-based natural antioxidants have a wide variety of biological activities with significant therapeutic value. Mangifera indica has been used traditionally to treat a variety of ailments in animals and human, but little is defined about its biological or pharmacological effects. Therefore, the objective of the present study was to evaluate phytochemical, antioxidant, antipyretic and anti-inflammatory activities of aqueous-methanolic leaf extract of M. indica. METHODS: To investigate the possible impact of aqueous-methanolic leaf extract of M. indica on oxidative stress, inflammation, and pyrexia, we used a combined in vitro and in vivo series of experiments on laboratory animals. RESULTS: Results revealed significant antioxidant potential in 2,2-diphenylpicrylhydrazyl (DPPH) and nitric oxide (NO) scavenging assay, while significant but dose dependent antipyretic potential was documented in typhoid-paratyphoid A and B (TAB) vaccine and prostaglandin E (PGE) induced pyrexia models. Significant anti-inflammatory effects were observed in both acute and chronic inflammatory models of arachidonic acid and formalin. Phytochemical screening and high-performance liquid chromatography (HPLC) analysis of M. Indica confirmed the presence of mangiferin, quercetin, and isoquercetin. These phytoconstituents likely play a role in the observed biological activities. Our results show that M. indica has antioxidant, anti-inflammatory, and antipyretic effects, lending credence to its traditional use and advocating for its utilization as a viable contender in treating oxidative stress-associated ailments. CONCLUSION: It is concluded that Magnifera indica has various properties in the treatment of various diseases.

Species composition, seasonal abundance and population dynamics of predatory spiders from cotton field plots of irrigated and semi-arid regions of Punjab, Pakistan.

The purpose of the current study was to document the variety of predatory spider species present in the cotton fields of two major cotton-producing districts in Punjab, Pakistan, as well as the population dynamics of those spiders. The research was carried out between May and October 2018 and 2019. Manual picking, visual counting, pitfall traps, and sweep netting were the procedures used to collect samples on a biweekly basis. A total of 10,684 spiders comprising 39 species, 28 genera, and 12 families were documented. Araneidae and Lycosidae families contributed a major share to the overall catch of spiders, accounting for 58.55 percent of the total. The Araneidae family's Neoscona theisi ) was the most dominating species, accounting for 12.80% of the total catch and being the dominant species. The estimated spider species diversity was 95%. Their densities were changed over time in the study, but they were highest in the second half of September and the first half of October of both years. The cluster analysis distinguished the two districts and the sites chosen. There was a relationship between humidity and rainfall and the active density of spiders; however, this association was not statistically significant. It is possible to increase the population of spiders in an area by reducing the number of activities detrimental to spiders and other useful arachnids. Spiders are considered effective agents of biological control throughout the world. The findings of the current study will help in the formulation of pest management techniques that can be implemented in cotton growing regions all over the world.

Pathogenetic Mechanisms of Liver-Associated Injuries, Management, and Current Challenges in COVID-19 Patients.

The global outbreak of COVID-19 possesses serious challenges and adverse impacts for patients with progression of chronic liver disease and has become a major threat to public health. COVID-19 patients have a high risk of lung injury and multiorgan dysfunction that remains a major challenge to hepatology. COVID-19 patients and those with liver injury exhibit clinical manifestations, including elevation in ALT, AST, GGT, bilirubin, TNF-α, and IL-6 and reduction in the levels of CD4 and CD8. Liver injury in COVID-19 patients is induced through multiple factors, including a direct attack of SARS-CoV-2 on liver hepatocytes, hypoxia reperfusion dysfunction, cytokine release syndrome, drug-induced hepatotoxicity caused by lopinavir and ritonavir, immune-mediated inflammation, renin-angiotensin system, and coagulopathy. Cellular and molecular mechanisms underlying liver dysfunction are not fully understood in severe COVID-19 attacks. High mortality and the development of chronic liver diseases such as cirrhosis, alcoholic liver disease, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatocellular carcinoma are also associated with patients with liver damage. COVID-19 patients with preexisting or developing liver disease should be managed. They often need hospitalization and medication, especially in conjunction with liver transplants. In the present review, we highlight the attack of SARS-CoV-2 on liver hepatocytes by exploring the cellular and molecular events underlying the pathophysiological mechanisms in COVID-19 patients with liver injury. We also discuss the development of chronic liver diseases during the progression of SARS-CoV-2 replication. Lastly, we explore management principles in COVID-19 patients with liver injury and liver transplantation.

Explorations of CRISPR/Cas9 for improving the long-term efficacy of universal CAR-T cells in tumor immunotherapy.

Chimeric antigen receptor (CAR) T therapy has shown remarkable success in discovering novel CAR-T cell products for treating malignancies. Despite of successful results from clinical trials, CAR-T cell therapy is ineffective for long-term disease progression. Numerous challenges of CAR-T cell immunotherapy such as cell dysfunction, cytokine-related toxicities, TGF-ß resistance, GvHD risks, antigen escape, restricted trafficking, and tumor cell infiltration still exist that hamper the safety and efficacy of CAR-T cells for malignancies. The accumulated data revealed that these challenges could be overcome with the advanced CRISPR genome editing technology, which is the most promising tool to knockout TRAC and HLA genes, inhibiting the effects of dominant negative receptors (PD-1, TGF-ß, and B2M), lowering the risks of cytokine release syndrome (CRS), and regulating CAR-T cell function in the tumor microenvironment (TME). CRISPR technology employs DSB-free genome editing methods that robustly allow efficient and controllable genetic modification. The present review explored the innovative aspects of CRISPR/Cas9 technology for developing next-generation/universal allogeneic CAR-T cells. The present manuscript addressed the ongoing status of clinical trials of CRISPR/Cas9-engineered CAR-T cells against cancer and pointed out the off-target effects associated with CRISPR/Cas9 genome editing. It is concluded that CAR-T cells modified by CRISPR/Cas9 significantly improved antitumor efficacy in a cost-effective manner that provides opportunities for novel cancer immunotherapies.

Exploring the effect of Jasmonic Acid for Aphids control for improving the yield of Triticum aestivum varieties.

Many biotic and abiotic factors influence the production of wheat (Triticum aestivum L.). Among biological agents, aphids are destructive pests effecting wheat yield drastically. This study was designed to evaluate the impact of foliar Jasmonic acid spray on aphid population as well as on plant growth during aphid infestation in two wheat varieties i.e., Borlaug-2015 and Zincol-2015. Plants are cultivated in pots and treated with jasmonic acid at concentrations of 0.1 and 1 mM (JA). The results revealed that length of shoot and roots decreased after aphid stress and was improved (21-24%) by JA spray. Photosynthetic pigments increased after applying the jasmonic acid spray compared to control plants. Jasmonic acid spray helped the plants to recover from aphid stress by enhanced production of antioxidant enzymes CAT (Catalase) (65-71%), SOD (Superoxide dismutase) (71-74%) and POD (Peroxidase) (61-65%). Consequent to improved defence system, plants treated with JA had fewer aphids as compared to control (60-73% reduction), 24 h after spray. The higher concentration of JA (1 mM) proved more effective as compared to 0.1 mM jasmonic acid. Moreover, Zincol-2015 appeared tolerant as compared to Borlaug-2015 against aphid infestation. The application of jasmonic acid as an exogenous foliar application showed an overall positive impact on the physiological and biochemical attributes of both varieties. It helps the plants to enhance resistance against the biotic stress and can be adopted as future alternative for aphid management. However, detailed studies regarding understanding of underlying molecular mechanisms are needed to optimize the mode for field application.

SARS-COV-2/COVID-19: scenario, epidemiology, adaptive mutations, and environmental factors.

The coronavirus pandemic of 2019 has already exerted an enormous impact. For over a year, the worldwide pandemic has ravaged the whole globe, with approximately 250 million verified human infection cases and a mortality rate surpassing 4 million. While the genetic makeup of the related pathogen (SARS-CoV-2) was identified, many unknown facets remain a mystery, comprising the virus's origin and evolutionary trend. There were many rumors that SARS-CoV-2 was human-borne and its evolution was predicted many years ago, but scientific investigation proved them wrong and concluded that bats might be the origin of SARS-CoV-2 and pangolins act as intermediary species to transmit the virus from bats to humans. Airborne droplets were found to be the leading cause of human-to-human transmission of this virus, but later studies showed that contaminated surfaces and other environmental factors are also involved in its transmission. The evolution of different SARS-CoV-2 variants worsens the condition and has become a challenge to overcome this pandemic. The emergence of COVID-19 is still a mystery, and scientists are unable to explain the exact origin of SARS-CoV-2. This review sheds light on the possible origin of SARS-CoV-2, its transmission, and the key factors that worsen the situation.

Anticancer L-Asparaginase and Phytoactive Compounds From Plant Solanum nigrum Against MDR (Methicillindrug resistant) Staphylococcus aureus and Fungal Isolates.

L-asparaginase is used in chemotherapy for acute lymphoblastic leukemia and other cancers. L-asparaginase derived from bacterial source triggers immune responses. The current study investigates Solanum nigrum as a novel and latent source of L-asparaginase to minimize immunological reactions. The antitumor activity of SN methanol extract was determined using the potato disc assay. InterPro Chimera and InterPro were used to predict the amino acid sequence of L-asparaginase and its anticancer activity. Purification of the enzyme was carried out to homogeneity of 1.51-fold with a recovery of 61.99%. At optimal conditions of 36.5°C, pH 8.6, and 8.5 g/mL substrate, fruit (crude extract) revealed an L-asparaginase titer of 48.23 U/mL. The molecular weight of the enzyme was calculated to be 32 ± 5 kDa using SDS PAGE. The fruit's total flavonoids and phenolic contents are 0.42 ± .030 g/mL and 94 ± 1.9 mg CAE, respectively. Anti-tumorigenic efficacy was determined to be 66% against Agrobacterium tumefaciens. Additionally, the extract possesses potent antifungal and antibacterial properties. Molecular docking provided the structural motifs and underlying interactions between L-asparaginase, N-acetylglucosamine, murine, and chitin. SN contains high levels of the enzyme L-asparaginase and phytochemicals, making it a potential source of anticancer drugs.

Clinical profile and screening of exon 6 and 14 of ABCB4 gene in obstetric cholestasis patients at a tertiary care hospital in Rawalpindi, Pakistan.

OBJECTIVE: Intrahepatic Cholestasis of Pregnancy (ICP) is a rare pregnancy specific disorder. Genetic variants of ABCB4 gene increase ICP risk. This study was conducted to determine frequency of ICP cases presented at a tertiary care hospital in Rawalpindi, Pakistan and to screen for genetic variants of exon 6 and 14 of ABCB4 gene in ICP cases. METHODS: This analytical study included ICP patients presenting at Department of Gynaecology and Obstetrics, Holy Family Hospital Rawalpindi, from February 2017 to May 2017. Sanger's sequencing was performed using genomic DNA extracted from blood samples of patients and controls. RESULTS: Twenty pregnant women out of 1150 (1.74%) had ICP and were enrolled during study period. Overall (19/20) 95% patients had pruritus and among them (8/20) 40%, (4/20) 20% and (2/20) 10% had a history of miscarriages, stillbirths and familial ICP respectively. Genetic analysis revealed an already reported variant i.e., c.504C>T in exon 6 in thirteen patients and a novel variant i.e., c.1686A>G in exon 14 in five patients. Both variants were not present in controls. In silico analysis suggested that both variants might affect pre-mRNA splicing of ABCB4 transcript. CONCLUSIONS: ICP had a frequency of 1.74% among pregnant women. Identification of a novel heterozygous variant in five patients and an already reported variant in thirteen patients reaffirms genetic heterogeneity and role of ABCB4 in ICP etiology.

Antidiarrheal and Cardio-Depressant Effects of Himalaiella heteromalla (D.Don) Raab-Straube: In Vitro, In Vivo, and In Silico Studies.

Himalaiella heteromalla (D.Don) Raab-Straube is a commonly used remedy against various diseases. Crude extract and fractions of H. heteromalla were investigated for a gastrointestinal, bronchodilator, cardiovascular, and anti-inflammatory activities. H. heteromalla crude extract (Hh.Cr) relaxed spontaneous contractions and K+ (80 mM)-induced contraction in jejunum tissue dose-dependently. The relaxation of K+ (80 mM) indicates the presence of Ca++ channel blocking (CCB) effect, which was further confirmed by constructing calcium response curves (CRCs) as they caused rightward parallel shift of CRCs in a manner comparable to verapamil, so the spasmolytic effect of Hh.Cr was due to its CCB activity. Application of Hh.Cr on CCh (1 µM) and K+ (80 mM)-induced contraction in tracheal preparation resulted in complete relaxation, showing its bronchodilator effect mediated through Ca++ channels and cholinergic antagonist activity. Application of Hh.Cr on aortic preparations exhibited vasorelaxant activity through angiotensin and α-adrenergic receptors blockage. It also showed the cardio suppressant effect with negative chronotropic and inotropic response in paired atrium preparation. Similar effects were observed in in vivo models, i.e., decreased propulsive movement, wet feces, and inhibition of edema formation.

A study of maternal mortality in 8 principal hospitals in Pakistan in 2009.

OBJECTIVES: To determine maternal mortality to assess the achievement of Millennium Development Goal 5 in Pakistan and suggest remedial measures. METHODS: Throughout 2009, maternal deaths occurring in obstetrics and gynecology departments in 8 hospitals in Rawalpindi and Islamabad, Pakistan, were recorded. A data form was filled in by the duty registrar at the time of death. Data were analyzed via SPSS. RESULTS: During the study period, there were 47209 live births and 108 maternal deaths (age 17-45 years). Among those who died, 30% were primigravidas, 50% had a parity of 1-4, and 20% had a parity of 5 or more; 20.4% had not delivered, 40.7% had vaginal delivery, and 36.1% had cesarean delivery; 67.6% were unbooked and 32.4% were booked (14 under care of a consultant and 21 under care of a medical officer); 73%, 22%, and 5% died in the first, second, and third trimesters, respectively; 17.5% died prenatally, 4.6% during labor, and 78% postpartum; 73% were in a critical condition and 8% were dead on arrival. Eclampsia, postpartum hemorrhage, and sepsis caused 23, 13, and 13 deaths, respectively. CONCLUSION: Maternal death can be effectively managed by skilled care during pregnancy, childbirth, and the postnatal period.