Dehydroepiandrosterone (DHEA), a circulating steroid hormone precursor produced potent vasorelaxation in rat aorta and mesenteric arteries through blockade of L-type voltage-dependent calcium channels.

Dehydroepiandrosterone (DHEA) is known for potent cardioprotective properties and diminished DHEA level in plasma is often associated with hypertension and age-related anomalies. However, putative ex-vivo vasorelaxation potential of DHEA in systemic resistance vessels like mesenteric arteries and conduit arteries like aorta are still to be worked out. The study aimed to explore vasorelaxation potential of DHEA in superior and resistance mesenteric arteries and aorta in rats and to determine the contribution L-type Voltage dependent calcium channel (L-VDCC) in the relaxation response in these arterial tissues.

Synthesis and optimization of molecular weight of chitosan and carboxymethyl cellulose based polyurethanes.

For the first time in this research, using a mixture design approach, polyurethanes (PUs) based on chitosan (CSN) and carboxymethyl cellulose (CMC) were synthesized to develop a high molecular weight polymer. In the synthesis process, a reaction between isophorone diisocyanate (IPDI) and hydroxyl-terminated polybutadiene was carried out to synthesize a prepolymer containing free NCO groups at the corners. This prepolymer was further reacted with changing moles ratio of CSN and CMC following the principles of statistical mixture design.

The SCR-17 and SCR-18 glycans in human complement factor H enhance its regulatory function.

Human complement factor H (CFH) plays a central role in regulating activated C3b to protect host cells. CFH contain 20 short complement regulator (SCR) domains and eight N-glycosylation sites. The N-terminal SCR domains mediate C3b degradation while the C-terminal CFH domains bind to host cell surfaces to protect these.

Transformative enhancement of cellulosic textile properties via metallic oxide deposition: Comprehensive analysis of structural, optical, and thermoelectric traits.

This novel research addresses the critical need for sustainable and efficient materials, aiming to enhance the optical and thermoelectric properties of Aluminum doped Zinc Oxide (Al-doped ZnO) on cellulose fabric for diverse applications. At first stage, Cellulosic fabric of Al-doped ZnO were experimentally studied in detail with respect to varying levels of annealing temperature. Structural analysis unveiled structural evolution in hexagonal crystal formations with a reduction in particle size up to 27.

Synthesis of 6-alkoxy and 6-hydroxy-alkyl amine derivatives of braylin as vasorelaxing agents.

Braylin (10b) is a 8,8-dimethyl chromenocoumarin present in the plants of the family Rutaceae and Meliaceae and possesses vasorelaxing and anti-inflammatory activities. In this study, six 6-alkoxy (10b, 15-19), and twelve 6-hydroxy-alkyl amine (20a-20l) derivatives of braylin (11 and 12) were synthesized to delineate its structural requirement for vasorelaxing activity. The synthesized compounds were evaluated for vasorelaxation response in preconstricted intact rat Main Mesenteric Artery (MMA).

Ormeloxifene, a selective estrogen receptor modulator, protects against pulmonary hypertension.

Purpose: Protective effect of 17β-estradiol is well-known in pulmonary hypertension. However, estrogen-based therapy may potentially increase the risk of breast cancer, necessitating a search for novel drugs. This study, therefore, investigated the ameliorative effects of a selective estrogen receptor modulator, ormeloxifene, in pulmonary hypertension.

A solution structure analysis reveals a bent collagen triple helix in the complement activation recognition molecule mannan-binding lectin.

Collagen triple helices are critical in the function of mannan-binding lectin (MBL), an oligomeric recognition molecule in complement activation. The MBL collagen regions form complexes with the serine proteases MASP-1 and MASP-2 in order to activate complement, and mutations lead to common immunodeficiencies. To evaluate their structure-function properties, we studied the solution structures of four MBL-like collagen peptides.

Priorities for pulmonary hypertension research: A James Lind Alliance priority setting partnership.

Pulmonary hypertension (PH) is a rare condition associated with significant morbidity and mortality. The priorities for future research in PH according to patients, caregivers, and clinicians have not been established. We performed a James Lind Alliance priority setting partnership in Canada.

2-Benzyllawsone protects against polymicrobial sepsis and vascular hyporeactivity in swiss albino mice.

Background: Novel naphthoquinone, 2-benzyllawsone (LT-9) was evaluated against vascular hyporeactivity and sepsis in cecal ligation and puncture (CLP) model in mice in view of its preliminary antibacterial and anti-inflammatory properties and to explore whether pretreatment with the molecule could restore vascular tone and contractile response to norepinephrine.

Methods: Evaluation of LT-9 against vascular hyporeactivity, hypotension, and sepsis-related inflammation and infection was carried out in the CLP model in Swiss albino mice and aortic smooth muscle cells in vitro.

Results: LT-9 showed potent reversal of the vascular hyporeactivity in CLP mice aorta.

Inhibition of Bruton Tyrosine Kinase Reduces Neuroimmune Cascade and Promotes Recovery after Spinal Cord Injury.

Microglia/astrocyte and B cell neuroimmune responses are major contributors to the neurological deficits after traumatic spinal cord injury (SCI). Bruton tyrosine kinase (BTK) activation mechanistically links these neuroimmune mechanisms. Our objective is to use Ibrutinib, an FDA-approved BTK inhibitor, to inhibit the neuroimmune cascade thereby improving locomotor recovery after SCI.

Design, synthesis and broad spectrum antibreast cancer activity of diarylindoles via induction of apoptosis in aggressive breast cancer cells.

Breast cancer is the second leading cause of cancer deaths in women with significant morbidity and mortality. Present study describes design, synthesis and detailed pharmacology of indole derivatives exhibiting remarkable broad spectrum antiproliferative activity against breast cancer cells. Detailed mechanistic evaluations confirmed induction of G0/G1 arrest, apoptosis induction, loss of mitochondrial integrity, enhanced ROS generation, autophagy, estrogen receptor β-transactivation and increased tubulin polymerization.

Antihypertensive Effect of a Novel Angiotensin II Receptor Blocker Fluorophenyl Benzimidazole: Contribution of cGMP, Voltage-dependent Calcium Channels, and BK Channels to Vasorelaxant Mechanisms.

The current study presents the novel angiotensin II receptor blocker fluorophenyl benzimidazole (FPD) as an antihypertensive agent in the SHR model of hypertension. We investigated the role of cGMP, voltage-dependent L-type calcium channels, and BK channels in the vasorelaxant mechanisms of FPD in the rat superior mesenteric artery. The antihypertensive effect of FPD was examined using an invasive technique measuring blood pressure in SHR animals.

Inhibition of Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 (MK2) is Protective in Pulmonary Hypertension.

[Figure: see text].

Standardization of Kaempferia galanga L. rhizome and vasorelaxation effect of its key metabolite ethyl p-methoxycinnamate.

Ethnopharmacological Relevance: Kaempferia galanga L. rhizome (KGR) is part of more than sixty-one Ayurvedic formulations and commonly known as 'Chandramula'. KGR is widely used in traditional Indian medicines to treat fever (jwar), rheumatism (Amavata), respiratory (Shwasa), hypertension (Vyanabala vaishamya) and cardiovascular disorders (Vyanavayu Dushtijanya Hrudrog).

Variability of Breast Density Assessment and the Need for Additional Imaging: A Comparison between Computed Mammography and Digital Mammography.

Objective: To determine the variability of breast density assessment and the need for additional imaging using computed radiography (CR) mammography versus digital radiography (DR) mammography.

Study Design: Cohort study.

Place And Duration Of Study: Department of Radiology, The Aga Khan University Hospital, Karachi from March to June 2018.

Antiproliferative activity of diarylnaphthylpyrrolidine derivative via dual target inhibition.

Breast cancer is the second leading cause of deaths in women globally. Present communication deals with design and synthesis of a few diarylnaphthyls as possible anti-breast cancer agents. Among the thirty three representatives with significant antiproliferative activity compounds 23 and 50 were quite efficacious against human breast cancer cells.

Synthesis and evaluation of substituted 8,8-dimethyl-8H-pyrano[2,3-f]chromen-2-one derivatives as vasorelaxing agents.

A series of substituted 8,8-dimethyl-8H-pyrano[2,3-f]chromen-2-ones (chromeno-coumarin hybrids) was synthesized from scopoletin (11) as vasorelaxing agents. The synthesized compounds 21a-f, 22, 23a-e and scopoletin (11) were evaluated for vasorelaxation in endothelium intact rat main mesenteric artery (MMA). Compounds 11, 21a, 21c-f and 22 showed significant vasorelaxation in precontracted MMA within the range of EC value 1.

Antihypertensive activity of diethyl-4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate: A continuation study in L-NAME treated wistar rats.

In the present study, we report that neolignan1 (Diethyl-4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate) relaxes the superior mesenteric artery in a concentration dependent manner (pD2 value 5.392 ± 0.04; n = 8 for endothelium intact and 5.

3-Arylindanones and related compounds as antiproliferative agents against colorectal cancer.

Diverse benzylidene indanones and their derivatives were synthesized as anticancer agents. Two of the analogues, that is 7 and 22, exhibited significant antiproliferative activity against several human cancer cell lines. Both the compounds possessed antimitotic activity and induced apoptosis in DLD1 colorectal adenocarcinoma cells through activation of caspase pathways.

Polypoid Adenomyoma of the Uterus.

Polypoid adenomyoma is a rare uterine endometrial polypoid tumor of mixed epithelial and mesenchymal origin. Although the clinical and pathologic features of polypoid adenomyomas have been described extensively, imaging findings for these tumors have not been frequently reported in the literature. On imaging, their features may be confused with prolapsed leiomyomas or malignancy.

Chest Wall Schwannoma: Case Report and a Review of Imaging Findings.

A chest wall schwannoma arises from peripheral nerve sheath Schwann cells of the intercostal nerves. We describe the presentation and imaging findings of a patient who presented with a chest wall swelling. The imaging findings were highly suspicious for a chest wall schwannoma and the histopathology confirmed the diagnosis following surgical excision.

Repositioning Flubendazole for Spinal Cord Injury.

We previously reported the serendipitous observation that fenbendazole, a benzimidazole anthelmintic, improved functional and pathological outcomes following thoracic spinal cord contusion injury in mice when administered pre-injury. Fenbendazole is widely used in veterinary medicine. However, it is not approved for human use and it was uncertain if only post-injury administration would offer similar benefits.

Diagnostic Accuracy of Ultrasound in Detecting Retained Products of Conception: A Study from a Tertiary Care Hospital in Karachi, Pakistan.

Introduction Retained products of conception (RPOC) are a known complication after abortion or childbirth. To improve clinical evaluation and avoid unnecessary surgery, transvaginal scan is performed in suspected cases. However, both RPOC and blood clots appear isoechoic on ultrasound, and false positives can lead to unnecessary intervention.