Pharmacological Evaluation of an Advanced Formulation of Curcumin to Prevent Breast Cancer Bone Metastases

Curcumin has low plasma concentration due to low water solubility and instability. We have formulated alendronate-conjugated curcumin nanoparticles (Aln-Cur-NPs) for the targeted delivery of the drug to the bone. This project aims to investigate the in vitro biological effects of Aln-Cur-NPs that are developed to prevent breast cancer bone metastasis. The loading capacity was found to be 4% and 5.7% for Aln-Cur-NP and Cur-NP, respectively. A significantly higher antitumor activity was observed for Aln-Cur-NP compared to Cur-NP with IC50 values of 13.9, 22.2 and 7.7 µg/mL for MCF-7, MDA-MB-231 and SK-BR-3, respectively. This study showed the enhanced anticancer activity of curcumin nanoparticles conjugated with alendronate compared to Cur-NPs, which strongly supports the synergistic effect of curcumin/bisphosphonates combination considering the similar amount of uptaken curcumin by the cancer cells for both nanoparticle formulations. The impact of nanoparticles on the viability of MDA-MB-231 cells was also investigated using recording time lapse image technology by IncuCyte® over two days. It was demonstrated that the uptake of raw curcumin was much less, and it precipitated outside the cells while, curcumin encapsulated in nanoparticles was effectively uptaken by the cancer cells. The qualitative analysis of confocal images showed higher uptake for Aln-Cur-NPs compared to raw curcumin (p ˂0.0001) and no uptake for the untreated (PBS) control. The effect of our Nanoparticles on the release of PTHrP was determined by PTHrP ELISA assay for quantitative measurement of human PTHrP concentration released by MDA-MB-231 cells. The results suggested the possibility of reducing osteolytic activity of the cancer cells in bone metastasis. These preliminary data suggest Aln-Cur-NPs can offer promises in preventing and treating breast cancer bone metastases

Evaluation of hepatoprotective effect of chloroform and methanol extracts of <i>Opuntia monacantha</i> in paracetamol-induced hepatotoxicity in rabbits

The chloroform and methanol extracts of Opuntia monacantha were studied for its hepatoprotective effect against paracetamol induced liver damage in rabbits. Results proved that both extracts at 200, 400 and 600 mg/kg body weight in one week protocol showed significant (p<0.001) hepatoprotective activity by reducing the magnitude of liver markers including alanine aminotransferase, aspartate aminotransferase, alkaline phasphatase and total bilirubin levels. The results were supported by histopathological studies of liver tissue. Chemical analysis of O. monacantha indicated the presence of alkaloids, tannins, saponins, flavonoids and  polysaccharides and its hepato-protective potential may be due to the presence of flavonoids. Its is concluded that 600 mg/kg is the potent dose of both extracts of O. monacantha as hepatoprotective plant

A Sociological Study about the Adoption of Contraception Methods and Their Effects on the Married Females’ Health in Rural Areas of Tehsil Dera Ghazi Khan-Pakistan

Population is growing rapidly &amp; adoption of FP has been neglected by Govt. of Pakistan due to lack of services, awareness and education, traditional believes, employment &amp; misconception. Mostly people think that the use of contraception methods is against the nature and Islam and is also harmful for health. So present study was designed in rural areas of Tehsil Dera Ghazi Khan in 2013 to investigate the knowledge level, adoption of contraception as well as to perceived positive and negative effects of contraception methods on the health of married females in rural community. 160 rural married females were interviewed to find out their demographic features; utilization of contraception and its side effects on their health in tehsil Dera Ghazi Khan. The data was analyzed by using Uni-variate (frequency distribution and percentage) and Bi-variate analysis (Chi square and Gamma Statistics) was carried out. Predominating age categories were &lt;15 and 16-20 years, 45.6% were illiterate, and 55.6% had good mutual understandings. More than one fifth (26.2%) had 1-2 pregnancies, 59.4% had sometimes heard about contraceptive methods while 84.4% had favorable attitude towards adoption of contraception methods. Whereas 58.1% had sometimes used contraceptive methods, 31.9% got information about contraceptive methods from relatives. In adoption of different contraception methods during the life span, respondents reported both types i.e. modern injections (60.6%), spermicides (50.6%), and in traditional methods i.e. withdrawal (6.2%); adoption of herbs (5.7%) and 44.4% had faced positive effects while 19.4% faced negative effects whereas 36.2% of the respondents had both type of effects (positive/ negative) on their health after the adoption of FP methods during reproductive span. Bi-variate analysis showed positive relationship between desired of family size and utilization of contraception, Freedom of decision making vs utilization of contraception methods and mutual understanding of spouse vs adoption of contraception method. There was a need to bring positive change in societal attitude for the utilization of family planning. Keywords: FP Methods, Contraception adoption, effects, Religious opinion, Decision making, Rural Females, Socio-economic statu

Comprehensive human health risk assessment of heavy metal contamination in urban soils: insights from selected metropolitan zones

Introduction: This study aims to assess the extent of heavy metal contamination in urban soils in sixteen selected cities of Pakistan, encompassing the elements cadmium (Cd), lead (Pb), cobalt (Co), zinc (Zn), chromium (Cr), nickel (Ni), manganese (Mn), iron (Fe), and copper (Cu).Methods: The data utilized for this study was collected from online literature during the period 2005 to 2019. This study investigated potential threats to human health through a comprehensive analysis, considering standards such as Enrichment Factors (EF), Geo-accumulation Indices (Igeo), and Human Health Risk Assessment (HHRA).Results: Geo-accumulation Index results indicated varied risk intensities, with Cu, Pb, Co, Mn, and Fe exhibiting “no pollution” levels, while other elements show “moderate to extremely contaminated” values. EF analysis provided evidence of heavy metal presence, revealing a spectrum from “no pollution” to “moderate to extremely high pollution” for Cd, Zn, Cr, Ni, and Cu. The health risk assessment identified both carcinogenic and non-carcinogenic dangers for adults and children.Discussion: These findings highlighted the substantial contribution of identified sources such as industrial processes, vehicular emissions, sewage sludge, urban flooding, and the production and use of metallic materials that have elevated heavy metal levels in the urban soils. This established the link between urban industrial zones, human health, and long-term economic sustainability. This study provides essential guidance for decision makers to develop effective strategies for soil remediation, enhanced industrial practices, and regulatory measures to address heavy metal contamination in urban areas, ensuring the wellbeing and sustainable environmental quality management in cities

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Different Targeting Strategies for Treating Breast Cancer Bone Metastases

Background: Breast cancer is the most frequently diagnosed malignancy in women worldwide. Breast cancer tends to metastasize to bone. Around 70% of the breast cancer patients eventually develop bone metastasis. After the bone invasion, metastatic cells disrupt the balance between osteoblastic and osteoclastic activities, leading to skeletal complications, characterized by pain and pathological fractures and hence worsening the patient's quality of life. Once tumor invades the bone, it is hard to treat it with, the so-far available treatments options (e.g. bisphosphonates and denosumab). Bone metastasis should be essentially controlled, in cancer treatment and there is a strong need to explore new, more efficient therapeutic targets. This review discusses the bone physiological processes and the recent advances in exploring different pathways involved in bone metastasis. Furthermore, some novel treatment options, which are under preclinical and clinical investigations, are highlighted. Conclusion: A deeper understanding of these metastatic pathways can provide oncology researchers with novel avenues for treating bone metastasis, one of the main challenges to cure breast cancer. The restoration of healthy bone environment will not only improve the patient's quality of life but also reduces the tumor burden. </jats:sec

The Salient Stylistic Features of Majeed Amjad

&nbsp;Stylistics is defined as the study of style, Phonetics, Morphology, Syntax and Semantics as tools of criticism, relatively modern sources of discovering hidden meaning and layers of expression. According Nills Erik Enkvist the style of a poet is analyzed through Language he used. He suggests this analysis upon the basis of two aspects of style. (1) Choice between alternative expressions. (2) Derivation from the norm. Majeed Amjad having unique style and poetics must be analyzed on modern parameters of stylistics. Majeed Amjad has his own distinguish style among the urdu poets. He carved out a new style other. He experimented with metrical forms and rhythms. Stylistic analysis of Amjad&rsquo;s poetry Lenlighteen the individual traits of his style. Stylistics choice of lexical items, phonetics, Morphological choices and grammatical sources shows distinctive features of his poetics and literary style

The Salient Stylistic Features of Majeed Amjad

&nbsp;Stylistics is defined as the study of style, Phonetics, Morphology, Syntax and Semantics as tools of criticism, relatively modern sources of discovering hidden meaning and layers of expression. According Nills Erik Enkvist the style of a poet is analyzed through Language he used. He suggests this analysis upon the basis of two aspects of style. (1) Choice between alternative expressions. (2) Derivation from the norm. Majeed Amjad having unique style and poetics must be analyzed on modern parameters of stylistics. Majeed Amjad has his own distinguish style among the urdu poets. He carved out a new style other. He experimented with metrical forms and rhythms. Stylistic analysis of Amjad&rsquo;s poetry Lenlighteen the individual traits of his style. Stylistics choice of lexical items, phonetics, Morphological choices and grammatical sources shows distinctive features of his poetics and literary style

The Salient Stylistic Features of Majeed Amjad

&nbsp;Stylistics is defined as the study of style, Phonetics, Morphology, Syntax and Semantics as tools of criticism, relatively modern sources of discovering hidden meaning and layers of expression. According Nills Erik Enkvist the style of a poet is analyzed through Language he used. He suggests this analysis upon the basis of two aspects of style. (1) Choice between alternative expressions. (2) Derivation from the norm. Majeed Amjad having unique style and poetics must be analyzed on modern parameters of stylistics. Majeed Amjad has his own distinguish style among the urdu poets. He carved out a new style other. He experimented with metrical forms and rhythms. Stylistic analysis of Amjad&rsquo;s poetry Lenlighteen the individual traits of his style. Stylistics choice of lexical items, phonetics, Morphological choices and grammatical sources shows distinctive features of his poetics and literary style.</p

The Salient Stylistic Features of Majeed Amjad

&nbsp;Stylistics is defined as the study of style, Phonetics, Morphology, Syntax and Semantics as tools of criticism, relatively modern sources of discovering hidden meaning and layers of expression. According Nills Erik Enkvist the style of a poet is analyzed through Language he used. He suggests this analysis upon the basis of two aspects of style. (1) Choice between alternative expressions. (2) Derivation from the norm. Majeed Amjad having unique style and poetics must be analyzed on modern parameters of stylistics. Majeed Amjad has his own distinguish style among the urdu poets. He carved out a new style other. He experimented with metrical forms and rhythms. Stylistic analysis of Amjad&rsquo;s poetry Lenlighteen the individual traits of his style. Stylistics choice of lexical items, phonetics, Morphological choices and grammatical sources shows distinctive features of his poetics and literary style.</p