Modulation of mammary tumour progression using murine model by ethanol root extract of Saussurea costus (falc.) lipsch.

ETHNOPHARMACOLOGICAL RELEVANCE: Breast cancer is a major cause of death among human females across the globe. The anti-neoplastic agents or therapies used for the treatment of cancers can enhance longevity but are subsequently observed to deteriorate the quality of life due to the extensive side effects produced. Saussurea costus is a potential medicinal plant of the Himalayas with noticeable ethnopharmacological properties. The phytochemicals present in Saussurea costus are responsible for anti-carcinogenic potential and warranted nil or minimal side effects of Saussurea costus and directed to use this plant as a preventive or therapeutic drug candidate against cancers. AIM OF THE STUDY: The present study was planned to evaluate the anti-neoplastic activity of Saussurea costus root extract (SL) in rat mammary tumour model. MATERIALS AND METHODS: The anti-neoplastic activity of SL root extract at 3 different doses (100, 250 and 500 mg/kg BW) for 18 weeks against 12-dimethylbenz (a) anthracene (DMBA)-induced mammary tumours in Sprague Dawley (SD) female rats was analyzed through serum biochemistry (ALT, AST, ALP, Total protein, Creatinine and BUN), oxidative stress parameters (Lipid peroxidation, Catalase and Reduced glutathione), pro-inflammatory cytokines (TNF-α and NF-κB), immunohistochemical markers (Ki-67, MMP-9 and VEGF), real-time PCR (PCNA, p53, bax, bcl-2 and caspase-3, genes) and molecular docking. RESULTS: Inhibition of tumour parameters, minimal alteration in the liver (ALT, AST and ALP) and kidney enzymes (Creatinine and BUN), decreased activity of MDA, elevated levels of GSH and catalase, reduction in the levels of pro-inflammatory cytokines i.e. TNF-α and NF-κB, reduced gross and histomorphological changes, declined expression of Ki-67, MMP-9 and VEGF in vivo rat model, mRNA expression of cancer-related genes and docking of dehydrocostus lactone and costunolide with NF-κB and TNF-α demonstrated the chemopreventive action of SL root extract. CONCLUSIONS: The in-vivo trial elucidates anti-neoplastic activity of Saussurea costus root extract as demonstrated through the reduction of biochemical indices, oxidative stress parameters, histological changes, pro-inflammatory cytokines (NF-κB and TNF-α), cellular proliferation (Ki-67), metastases (MMP-9) and neovascularization (VEGF) markers with highest anti-neoplastic effect of SL extract at the dose of 500 mg/kg body weight. Therefore, the present study signifies the need to use the active principles present in the root extract of Saussurea costus against breast cancer as a therapeutic regimen.

Randomized Controlled Trial Comparing Ferrous Sulfate and Iron Sucrose in Iron Deficiency Anemia in Pregnancy.

INTRODUCTION:  Anemia among pregnant women is one of the major health concerns for healthcare workers. The management becomes a concern in the pregnancy where the question arises of which is better the intravenous iron sucrose or the oral ferrous sulfate tablets. To answer this, a randomized control trial comparing both the treatment options in a tertiary care government hospital was set up in the hilly terrains of India. This study discusses the effectiveness and practical aspect of using both, which seems to be the better out of both, and why. METHODS:  The study was conducted as a parallel-group, open-label randomized controlled trial (RCT) in the Department of Obstetrics and Gynecology of a tertiary care government hospital in India, with approximately 4,000 delivery loads annually. Ethical clearance was obtained from the institute's ethics committee (IEC), and the trial was registered with the Clinical Trial Registry of India (REF/2022/06/055013). Two hundred sixty-eight pregnant women between 18 and 45 years of age with moderate iron deficiency anemia (IDA) (hemoglobin (Hb) 7-9g/dl, microcytic-hypochromic, and serum ferritin <30ng/ml) were included in the study. Patients were randomly divided into two groups: group 1 with 134 patients to receive intravenous iron sucrose and group 2 with 134 patients to receive oral ferrous sulfate tablets. RESULTS: The intravenous iron sucrose is superior in terms of tolerability and correction of iron deficiency anemia during pregnancy. CONCLUSION: It yields a quicker rise in Hb and serum ferritin with no major side effects. In the difficult terrain of Himachal Pradesh, this makes IV iron sucrose a better option for anemic pregnant women who do not have easy access to health facilities resulting in a large number of them reaching hospitals with moderate to severe anemia at a later gestation.

Myelodysplastic Syndromes and Modalities of Treatment: An Updated Literature Review.

Myelodysplastic syndromes (MDS) represent a large group of rare and diverse clonal stem cell disorders. These are classified into several different phenotypes and typically arise following a multistep genetic process, whereby genetic mutations alter the DNA damage and cellular stress responses, impacting transcription, RNA splicing, epigenetics, and cytokine signaling. However, despite the advances made regarding molecular pathophysiology and prognostic criteria and the influx of new treatment modalities, management is primarily based on prognostic scores, such as the Revised International Prognostic Scoring System. This poses a significant challenge to current healthcare professionals due to poor comprehension of the underlying pathophysiology. Hence, this review integrates the latest research and treatment modalities for MDS and discusses the different genetic mutations outlined in the revised World Health Organization 2016 MDS classification system and the associated treatment modalities. Additionally, future directions of research and clinical management of MDS are discussed.

Anterior Cruciate Ligament Injury: Conservative Versus Surgical Treatment.

The most frequent type of ligament injury is an anterior cruciate ligament (ACL). The mechanisms of an ACL injury are classified as direct contact, indirect contact, and non-contact. Physical examination for the assessment of the ACL is commonly used in routine care in the evaluation of the knee and is part of the diagnostic process. Due to the high degree of variability in their presentation and outcomes, treatment must be tailored according to factors such as patient demographics, the severity of the damage, and long-term improvement profile. When it comes to ACL injuries, low-quality data have been produced that reveals no difference in patient-reported knee function results between surgical ACL restoration and conservative therapy. However, these results must be evaluated in the perspective of the fact that many individuals with an ACL rupture remained symptomatic after rehabilitation and eventually underwent ACL reconstruction surgery. This article has reviewed the risk factors and the mechanisms that commonly lead to ACL injuries. This article has also discussed the clinical significance of conservative and surgical management and has highlighted the implications of both approaches.

Acromegaly and the Colon: Scoping Beyond the Pituitary.

Acromegaly is a complex endocrinological disorder commonly caused by hypersecretion of growth hormone (GH) typically due to pituitary gland tumors. Patients with acromegaly who are successfully treated and biochemically managed have a reasonably average life expectancy. However, it causes a cascade of multi-systemic involvement throughout the patient's life, including cardiovascular, neuropsychiatric, respiratory, metabolic, neurological, neoplastic, and gastrointestinal involvement, resulting in a higher rate of hospitalization, lower quality of life, and a shorter life expectancy. Although cardiovascular complications are the primary cause of death in patients with acromegaly, malignancy is now emerging as a major killer in these individuals. Colorectal carcinoma has been reported to be prevalent in acromegaly individuals. This review article has compiled studies to demonstrate a link between acromegaly and colorectal neoplasia, intending to provide a strong foundation for their clinical relationship. This article has summarised a potential pathogenic mechanism and provided insights into the clinical presentation of such patients. Furthermore, this article has provided a brief overview of current screening recommendations for colorectal neoplasia in acromegaly patients.

Persistent Pulmonary Hypertension: A Look Into the Future Therapy.

Persistent pulmonary hypertension (PPHN) of the newborn is a lung parenchymal disorder that causes a wide range of hemodynamic changes in the newborn's systemic circulation. Arising from a multifactorial web of etiology, PPHN is one of the most common reasons for neonatal intensive care unit hospitalization and is associated with increased morbidity and mortality. Historically, multiple treatment modalities have been explored, ranging from oxygen and surfactant therapy to newer upcoming medications like magnesium sulfate and adenosine. This review article has discussed the pathogenesis of PPHN and its relationship with the clinical implications of PPHN, such as heart failure and so on. This article has also explored the diagnostic guidelines and analyzed the existing and the upcoming modalities for treating PPHN.