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Breast cancer is the most common cancer type and a primary cause of cancer mortality among females worldwide. Here, we analyzed the anticancer efficacy of a novel bromochlorinated monoterpene, PPM1, a synthetic analogue of polyhalogenated monoterpenes from Plocamium red algae and structurally similar non-brominated monoterpenes. PPM1, but not the non-brominated monoterpenes, decreased selectively the viability of several triple-negative as well as triple-positive breast cancer cells with different p53 status without significantly affecting normal breast epithelial cells. PPM1 induced accumulation of triple-negative MDA-MB-231 cells with 4N DNA content characterized by decreased histone H3-S10/T3 phosphorylation indicating cell cycle arrest in the G2 phase. Western immunoblot analysis revealed that PPM1 treatment triggered an initial rapid activation of Aurora kinases A/B/C and p21Waf1/Cip1 accumulation, which was followed by accumulation of polyploid >4N cells. Flow cytometric analysis showed mitochondrial potential disruption, caspase 3/7 activation, phosphatidylserine externalization, reduction of the amount polyploid cells, and DNA fragmentation consistent with induction of apoptosis. Cell viability was partially restored by the pan-caspase inhibitor Z-VAD-FMK indicating caspase contribution. In vivo, PPM1 inhibited growth, proliferation, and induced apoptosis in MDA-MB-231 xenografted onto the chick chorioallantoic membrane. Hence, Plocamium polyhalogenated monoterpenes and synthetic analogues deserve further exploration as promising anticancer lead compounds.

The family of polyhalogenated monoterpenes from Plocamium counts over a hundred known members. Using glyceraldehyde acetonide as a chiral-pool precursor, an enantioselective and divergent strategy was developed that provides a blueprint for the synthesis of many of the small yet complex acyclic members of this family. The broad applicability of this approach is demonstrated with the short, eight-step synthesis of four natural products and three analogues. These syntheses are the first of any members of the acyclic polyhalogenated Plocamium monoterpenes and permitted the evaluation of their selectivity against a range of tumor cell lines.

The main cause of cancer death among women is breast cancer. The most common type of breast cancer is the estrogen receptor positive breast cancer. Discovery of estrogen receptor provided a highly effective target for treatment of hormone-dependent breast cancer. Selective estrogen receptor inhibitors are useful for halting the growth of breast cancer cells and inducing apoptosis. Tamoxifen, a popular selective estrogen receptor modulator, can treat breast cancer but also has unfavourable side effects due to its estrogenic activity in other tissues. Many herbal remedies and bioactive natural compounds, such as genistein, resveratrol, ursolic acid, betulinic acid, epigallocatechin-3-gallate, prenylated isoflavonoids, zearalenol, coumestrol, pelargonidin, delphinidin, and biochanin A, have the ability to specifically modulate the estrogen receptor alpha. Moreover, several of these compounds speed up cell death by supressing estrogen receptor gene expression. This opens wide avenue to introduce number of natural medicines with a revolutionary therapeutic impact and few side effects. [ABSTRACT FROM AUTHOR]

Introduction: This research explores sustainable applications for waste generated from fenugreek (Trigonella foenum‐graecum), a plant with both nutritional and medicinal uses. The study specifically targets waste components as potential sources of nutrients and bioactive compounds. Objectives: The focus is to conduct detailed metabolic profiling of fenugreek waste, assess its anti‐inflammatory properties by studying its cyclooxygenase (COX) inhibitory effect, and correlate this effect to the metabolite fingerprint. Materials and Methods: Ethanolic extracts of fenugreek fruit pericarp and a combination of leaves and stems were subjected to untargeted metabolic profiling using liquid chromatography–mass spectrometry integrated with online database searches and molecular networking as an effective dereplication strategy. The study also scrutinized the COX inhibitory capabilities of these extracts and saponin‐rich fractions prepared therefrom. Molecular docking was employed to investigate the specific interactions between the identified saponins and COX enzymes. Results: The analysis led to the annotation of 81 metabolites, among which saponins were predominant. The saponin‐rich fraction of the fruit pericarp extract displayed the strongest COX‐II inhibitory activity in the in vitro inhibition assay (IC50 value of 81.64 ± 3.98 μg/mL). The molecular docking study supported the selectivity of the identified saponins towards COX‐II. The two major identified saponins, namely, proto‐yamogenin 3‐O‐[deoxyhexosyl (1 → 2)] [hexosyl (1 → 4)] hexoside 26‐O‐hexoside and trigofenoside A, were predicted to have the highest affinity to the COX‐II receptor site. Conclusion: In the present study, we focused on the identification of COX‐II inhibitory saponins in fenugreek waste through an integrated approach. The findings offer valuable insights into potential anti‐inflammatory and cancer chemoprotective applications of fenugreek waste. The ethanolic extracts of fenugreek wastes were subjected to LC‐MS/MS untargeted metabolic profiling and molecular networking, leading to the annotation of 81 metabolites, with saponins being major constituents. A saponin‐rich fraction was prepared from each waste extract. The COX inhibitory effect of the waste extracts and saponin‐rich fractions was evaluated. The saponin‐rich fractions showed a preferential COX‐II inhibition that was stronger than the ethanolic extracts. Molecular docking proved the selectivity of the identified saponins towards COX‐II enzyme. [ABSTRACT FROM AUTHOR]

Bacterial resistance to antibiotics poses a high level of danger worldwide. Bacterial resistance mechanisms are spreading globally, impeding our ability to treat common infectious diseases. Misuse and overuse of antibiotics accelerate microbial resistance to antibiotics. Despite the exerted efforts, none of the newly developed antibiotics are expected to be effective against the dangerous forms of antibiotic-resistant bacteria. Since many plants have been shown to contain powerful antimicrobial compounds that can act synergistically or alternatively to antibiotics, the demand for herbal medicines has recently increased to cotreat microbes that are resistant to antibiotics. Maximum benefit can be achieved when the pharmacokinetics and pharmacodynamics of natural products match the antibiotic. This review article refers to nine highly effective and key herbs to use alongside antibiotics to overcome crises of antibiotic resistance. Their unique molecular mechanisms of action have been highlighted. [ABSTRACT FROM AUTHOR]

Dolomiaea costus (Falc.) Kasana & A.K. Pandey Family Asteraceae, formerly known as Saussurea costus (Falc.) Lipsch contains a rich treasury of diverse bioactive compounds such as monoterpenes, sesquiterpenes, triterpenes, sterols, cardenolides, flavonoids, coumarins, lignans, phenylpropanoids and alkaloids. The sesquiterpene lactones, costunolide and dehydrocostuslactone in D. costus, possess unique promising in vitro and in vivo biological activities for the prevention and cure of diverse ailments like Parkinson's disease, oxidative stress, hyperpigmentation, ulcerative colitis, breast cancer, hepatocellular carcinoma, colon cancer, prostate cancer, ovarian cancer, leukemia, stomach cancer, prostate cancer, lung cancer, osteosarcoma, neuroblastoma, allergy, type 2 diabetes, hepatotoxicity, bronchitis, pulmonary fibrosis, thrombosis and various microbial infections. Costunolide and dehydrocostuslactone are potential drug candidates that could lead to the development of new medications for a variety of difficult-to-treat diseases. [ABSTRACT FROM AUTHOR]

Background: Volume contraction frequently contributes to the development of acute kidney injury. The rapid assessment of volume status in patients with acute kidney injury could improve decision making and outcomes. Methods: The maximum and minimum diameters and percent collapsibility of the inferior vena cava (IVC) were measured in 30 patients admitted to the medical intensive care unit with laboratory evidence of acute kidney injury. These measurements were made on the day of admission and 24 hours following admission. Information about age, gender, body mass index, serum creatinine levels, and fluid balances was recorded. Results: This study included 30 patients with a mean age is 62.4 ±16.0 years. The mean initial creatinine was 4.3 ± 4.2 mg/dL (range: 1.7 mg/dL to 22.1 mg/dL). The mean fractional excretion of sodium was 2.06 ± 2.65%. The mean maximum diameter of inferior vena cava was 1.8 ± 0.5 cm with the range is 0.4-2.65 cm. The mean percent collapse was 32 ± 20%. Five patients had evidence of hypovolemia using guidelines from the American Society of Echocardiology; 6 patients had evidence of hypervolemia. Nineteen patients had measurements between these 2 categories. There is no significant change in mean diameters following fluid administration for 24 hours. An initial IVC diameter of 0.94 cm predicted ≥ 30% collapsibility with an area under the curve is 0.748. Discussion: Patients with acute kidney injury based on laboratory measurements had evidence for hypovolemia, euvolemia, and hypervolemia based on IVC measurements. There was no consistent change in IVC dimensions following fluid administration, even though the creatinine fell in most patients. Simple bedside measurements of IVC dimensions can facilitate fluid administration decisions but must be used with clinical assessment.

Drugs, including those used during diagnostic procedures, can have adverse effects and potentially serious side-effects, especially in complicated patients with significant comorbidity. Benzocaine is frequently used as an oropharyngeal anesthetic agent during bronchoscopy, transesophageal echocardiography, and upper GI endoscopy and can cause methemoglobinemia, a potentially life-threatening event if not diagnosed and treated quickly. Co-oximetry is the gold standard for the diagnosis of methemoglobinemia and can quantitate blood levels, which in turn correlate with the clinical presentation and the urgency for treatment. Methylene blue is the treatment of choice for methemoglobinemia. In this case report we discuss the pathophysiology, the clinical presentation, the diagnosis, and the treatment of benzocaine-induced methemoglobinemia.

Breast cancer is the most devastating disease for women. There is a great demand for new sources to treat this disease. Medicinal plants are an indispensable source of bioactive compounds with wide range of pharmacological activities. In-vitro cytotoxic activity of Otostegia fruticosa methanolic extract against human breast cancer was studied using MCF-7 cell line. The extract showed mildly potent activity (IC50 = 51 ± 9.836 µg/mL) in comparison to the standard anticancer doxorubicin (IC50 = 7.467 ± 1.05 µg/mL). Potential compounds responsible for activity have been identified using Molecular Operating Environment (MOE) module on the major compounds detected by HPLC-MS/MS technique against estrogen alpha receptor (ERα+: PDB ID 2JF9). 3,5-di-O-dicaffeoylquinic acid, hyperoside and rutin showed similar binding and antagonistic interaction with the estrogen alpha receptor as tamoxifen in several poses. The retrieved results confirm that we can add this plant to a powerful arsenal that combats this insidious disease. [ABSTRACT FROM AUTHOR]

The ink that cephalopods secrete to hide and frighten the enemies contains a treasury rich in bioactive diverse compounds like DOPA, melanin, melanin synthase, tyrosinase, angiotensin converting enzyme, catecholamines, oligopeptides, polyphenols, flavonoids, alkaloids, polysaccharides, fatty acids and minerals. These groups of the aforementioned compounds have promising unique in-vitro and in-vivo biological activities like antioxidant activity, anti-inflammatory, vasopressin, anti-Parkinson, anti-cancer, anti-coagulant, antimicrobial, anti-retroviral, anti-ulcerogenic and immune boosting activities. Cephalopods ink can be offered in its raw state or after separation and purification of its chemical constituents for use as natural medicine to treat many diverse diseases. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease. Heart failure may lead to acute kidney injury and vice versa. Chronic kidney disease may affect the clinical outcomes in patients with cardiovascular disorders. Renal impairment with any degree of albuminuria has been increasingly recognized as an independent risk factor for cardiovascular events and heart failure hospitalizations, while chronic heart failure may cause chronic kidney disease. The bidirectional nature of these disorders contributes to the complexity and the composite definitions of cardiorenal syndromes. However, the most important clinical trials in heart failure tend to exclude patients with significant renal dysfunction. The mechanisms whereby renal insufficiency worsens the outcome in heart failure are not known, and several pathways could contribute to the ‘‘vicious heart/kidney circle.’’ Traditionally, renal impairment has been attributed to the renal hypoperfusion due to reduced cardiac output and decreased systemic pressure. The hypovolemia leads to sympathetic activity, increased renin-angiotensin aldosterone pathway, and arginine-vasopressin release. These mechanisms cause fluid and sodium retention, peripheral vasoconstriction, and volume overload. Therapy to improve renal dysfunction, reduce neurohormonal activation and ameliorate renal blood flow could lead to a reduction in mortality and hospitalization in patients with cardiorenal syndrome.

As a result of our continuous research efforts to investigate the molecular mechanisms of Eucalyptus kino polyphenolics for healing liver solid tumors, in-vivo histopathological studies of the solid tumor tissues and in-silico molecular docking were carried out. Histopathology of female mice treated with a dose of 200 mg/kg Eucalyptus kino methanolic extract in combination with low level ionising γ-radiation (0.25 Gy) recovered a near-to-normal histological structure revealing a substantial number of cells with hyper-chromachia in nuclei, fibroblast lobules and necrotic cells. Analysis for matrix metalloproteinase-9 (MMP-9) by Western blot and also molecular docking study were conducted to evaluate and rank the potential of the individual components dominated in the extract to inhibit MMP-9 and TGF-β. The current study presents new lead compounds for the design of novel MMP-9 and TGF-β strong inhibitors of natural origin. [ABSTRACT FROM AUTHOR]

We are reporting a case of familial thoracic aortic aneurysm and dissection in a 26-year-old man with no significant past medical history and a family history of dissecting aortic aneurysm in his mother at the age of 40. The patient presented with cough, shortness of breath, and chest pain. Chest X-ray showed bilateral pulmonary infiltrates. CT scan of the chest showed a dissection of the ascending aorta. The patient underwent aortic dissection repair and three months later he returned to our hospital with new complaints of back pain. CT angiography showed a new aortic dissection extending from the left carotid artery through the bifurcation and into the iliac arteries. The patient underwent replacement of the aortic root, ascending aorta, total aortic arch, and aortic valve. The patient recovered well postoperatively. Genetic studies of the patient and his children revealed no mutations in ACTA2, TGFBR1, TGFBR2, TGFB2, MYH11, MYLK, SMAD3, or FBN1. This case report focuses on a patient with familial TAAD and discusses the associated genetic loci and available screening methods. It is important to recognize potential cases of familial TAAD and understand the available screening methods since early diagnosis allows appropriate management of risk factors and treatment when necessary.