Green Synthesis of Silver Nanoparticles and their Potential Applications in Mitigating Cancer.

In recent years, the field of nanotechnology has brought about significant advancements that have transformed the landscape of disease diagnosis, prevention, and treatment, particularly in the realm of medical science. Among the various approaches to nanoparticle synthesis, the green synthesis method has garnered increasing attention. Silver nanoparticles (AgNPs) have emerged as particularly noteworthy nanomaterials within the spectrum of metallic nanoparticles employed for biomedical applications. AgNPs possess several key attributes that make them highly valuable in the biomedical field. They are biocompatible, cost-effective, and environmentally friendly, rendering them suitable for various bioengineering and biomedical applications. Notably, AgNPs have found a prominent role in the domain of cancer diagnosis. Research investigations have provided evidence of AgNPs' anticancer activity, which involves mechanisms such as DNA damage, cell cycle arrest, induction of apoptosis, and the regulation of specific cytokine genes. The synthesis of AgNPs primarily involves the reduction of silver ions by reducing agents. Interestingly, natural products and living organisms have proven to be effective sources for the generation of precursor materials used in AgNP synthesis. This comprehensive review aims to summarize the key aspects of AgNPs, including their characterization, properties, and recent advancements in the field of biogenic AgNP synthesis. Furthermore, the review highlights the potential applications of these nanoparticles in combating cancer.

Synthetic and Natural Bioactive Molecules in Balancing the Crosstalk among Common Signaling Pathways in Alzheimer's Disease: Understanding the Neurotoxic Mechanisms for Therapeutic Intervention.

The structure and function of the brain greatly rely on different signaling pathways. The wide variety of biological processes, including neurogenesis, axonal remodeling, the development and maintenance of pre- and postsynaptic terminals, and excitatory synaptic transmission, depends on combined actions of these molecular pathways. From that point of view, it is important to investigate signaling pathways and their crosstalk in order to better understand the formation of toxic proteins during neurodegeneration. With recent discoveries, it is established that the modulation of several pathological events in Alzheimer's disease (AD) due to the mammalian target of rapamycin (mTOR), Wnt signaling, 5'-adenosine monophosphate activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), and sirtuin 1 (Sirt1, silent mating-type information regulator 2 homologue 1) are central to the key findings. These include decreased amyloid formation and inflammation, mitochondrial dynamics control, and enhanced neural stability. This review intends to emphasize the importance of these signaling pathways, which collectively determine the fate of neurons in AD in several ways. This review will also focus on the role of novel synthetic and natural bioactive molecules in balancing the intricate crosstalk among different pathways in order to prolong the longevity of AD patients.

The PCOS puzzle: putting the pieces together for optimal care.

Polycystic ovary syndrome (PCOS) is a multifaceted hormonal disorder that has significant ramifications for both women's reproductive and metabolic well-being. This analysis aims to offer a thorough comprehension of PCOS by investigating the various contributing factors that are crucial for its effective management. We delve into the topic of hormonal imbalances, such as elevated androgens and disrupted estrogen-progesterone dynamics, and their effects on reproductive and metabolic health. Furthermore, we explore the intricate connection between insulin resistance, hyperinsulinemia, and PCOS, highlighting their pivotal role in metabolic dysfunction. Additionally, we examine fertility challenges, irregular menstrual patterns, and metabolic complications while also reviewing current treatment methodologies. Moreover, we address the latest research concerning genetic, environmental, and epigenetic influences on PCOS. By piecing together these essential elements, healthcare professionals can attain a comprehensive understanding of PCOS and deliver optimal care for those affected by the condition.

A Comprehensive Review on Journey of Pyrrole Scaffold Against Multiple Therapeutic Targets.

Heterocyclic compounds are that type of substances that are deeply intertwined with biological processes. Heterocycles are found in about 90% of commercially available medicines. In medicinal chemistry, finding new synthetic molecules with drug-like characteristics is a regular problem, which triggered the development of pharmacological molecules, the majority of which are based on N-heterocyclic motifs. Among the heterocycles, the pyrrole scaffold is the most commonly found heterocycle in both natural and synthetic bioactive compounds. Pyrrole has a fivemembered heterocyclic ring with a plethora of pharmacophores, resulting in a library of different lead compounds. Pyrrole derivatives are physiologically active heterocyclic compounds that can be used as scaffolds for antibacterial, antiviral, anticancer, antitubercular, anti-inflammatory, and as enzyme inhibitors. On account of their extensive pharmacological profile, pyrrole and its various synthetic derivatives have drawn much attention from researchers to explore it for the benefit of humankind. This review presents an overview of recent developments in the pyrrole derivatives against multiple therapeutic targets.

Anticancer Potential of Thymoquinone: A Novel Bioactive Natural Compound from Nigella sativa L.

Cancer involves the uncontrolled division of cells resulting in abnormal cell growth due to various gene mutations and is considered the second major cause of death. Due to drug resistance to current anticancer drugs, cancer incidence is rising, and seeking effective treatment is a major concern. Natural products are prospective to yield unique molecules, as nature is a leading source of various drug molecules due to plenty of pharmacologically active molecules. Thymoquinone, a bioactive constituent obtained from Nigella sativa L., has drawn considerable attention among researchers in recent years due to its anticancer potential involving various molecular targets, including initiation of apoptosis initiation, arrest of cell cycle and generation of ROS, besides targeting multiple kinases such as tyrosine kinase, MAPK, and Janus kinase. The current review summarizes the thymoquinone chemistry, sources and anticancer potential involving various molecular targets.

Treatment Strategies Against Triple-Negative Breast Cancer: An Updated Review.

Triple-negative breast cancer (TNBC) is associated with an increased risk of early recurrence and distant metastasis, as well as the development of therapeutic resistance and poor prognosis. TNBC is characterized by a wide range of genetic, immunophenotypic, morphological, and clinical features. TNBC is coined to describe cancers that lack estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). As a result, hormonal or trastuzumab-based treatments are ineffective in TNBC patients. TNBCs are biologically aggressive, and despite some evidence that they respond to treatment better than other forms of breast cancer, the prognosis remains poor. This is attributed to a shorter disease-free interval in adjuvant and neoadjuvant settings, as well as a more aggressive metastatic course. TNBC has a lot of clinical ramifications. In terms of new treatment methods, TNBC has lagged behind other types of breast cancer. There are not many options for treating this form of breast cancer because it is progressive. Many effective treatments for most breast cancers block the growth-stimulating effects of ER, PR, and/or HER2, leaving TNBC with few choices. Finding new and effective treatment options for TNBC remains a critical clinical need. To develop more effective drugs, new experimental approaches must be tested in patients with TNBC.

An up to date on clinical prospects and management of osteoarthritis.

The rising prevalence of osteoarthritis (OA) in the general population has necessitated the development of novel treatment options. It is critical to recognize the joint as a separate entity participating in degenerative processes, as well as the multifaceted nature of OA. OA is incurable because there is currently no medication that can stop or reverse cartilage or bone loss. As this point of view has attracted attention, more research is being directed toward determining how the various joint components are impacted and how they contribute to OA pathogenesis. Over the next few years, several prospective therapies focusing on inflammation, cartilage metabolism, subchondral bone remodelling, cellular senescence, and the peripheral nociceptive pathway are predicted to transform the OA therapy landscape. Stem cell therapies and the use of various biomaterials to target articular cartilage (AC) and osteochondral tissues are now being investigated in considerable detail. Currently, laboratory-made cartilage tissues are on the verge of being used in clinical settings. This review focuses on the update of clinical prospects and management of osteoarthritis, as well as future possibilities for the treatment of OA.

Depression and anxiety in women with polycystic ovarian syndrome: a literature survey.

Polycystic ovarian syndrome (PCOS) is the most frequent endocrine disorder among women of reproductive age. Some of the indications and symptoms of PCOS include amenorrhoea, hirsutism, infertility, obesity, acne vulgaris and androgenic alopecia. PCOS is a crippling condition that affects a woman's identity, mental health and overall quality of life (QOL). In persons with PCOS, anxiety and sadness are assumed to be multifactorial. According to some specialists, physical symptoms like acne, hirsutism and obesity have been linked to psychiatric morbidities. Many aspects of it remain unknown, including its cause, progression throughout life, symptom spectrum and level of morbidity. PCOS is a complex disease that has an impact on many aspects of a person's health, including their mental health. Anxiety and depression are three times as common in PCOS patients as in non-PCOS people. Anxiety and depression symptoms are also more common and more intense in those with PCOS. There isn't enough research on the prevalence of anxiety and depression in patients with PCOS. It's unclear what causes persons with PCOS to be more anxious and depressed. It could be the result of PCOS symptoms, hormonal changes, or a combination of factors that are currently unclear. Our review article will help to highlight the most recent research on anxiety and depression in PCOS women.

Menstrual distress in females of reproductive age: a literature review.

Menstrual-related issues have significant public-health ramifications. Women who are having menstruation troubles should get their mental health checked by healthcare specialists. In young women, a menstrual-related condition has serious health implications. Young females who have menstrual issues miss job and school, and their behavioural and mental development suffers as a result. Depression and anxiety have an impact on women's menstrual periods in adults. Symptoms like as cramps, tiredness, backache, swelling abdomen, and painful breasts have also been described in women with menstrual misery. Menstrual distress has been shown to impair women's daily activities, as well as their reproductive and psychological health, according to research. Menstrual periods are frequently accompanied by a variety of unpleasant symptoms, such as premenstrual syndrome, which includes symptoms such as mild cramping and exhaustion. The severity of these symptoms, on the other hand, differs from woman to woman, depending on their health, food, way of life, and other factors. Women with menstrual-related issues have also reported smoking, alcohol intake, and an increase in hunger. Furthermore, young women experience emotional disturbances such as melancholy, restlessness, and despair. It is a sign of an atypical menstrual cycle if there is no cycle or if the bleeding is atypical or light. As a result, it is critical to maintain contact with a gynaecologist in order to detect any significant changes in a regular menstrual cycle.

Polycystic ovary syndrome and infertility: an update.

Polycystic ovarian syndrome is the most well-known endocrine condition among women of this generation (PCOS). Symptoms of hyperandrogenism, irregular menstrual periods, and insulin resistance are all traits associated with PCOS. In women with PCOS, the chance of having problems including infertility, insulin resistance, and type 2 diabetes increases. The PCOS board hopes to reduce body weight and insulin levels, restore fertility, control excessive hair growth on the body or scalp, re-establish the regular feminine cycle, and avoid misunderstandings. Insulin sensitizers have been one of the most common metabolic modulators, but their effectiveness has been sporadic. Insulin resistance, followed by thiazolidinediones, is central to the pathophysiology of PCOS, with metformin having nearly similar efficacy. In the management of PCOS, statins and incretins are newer therapies with obvious metabolic targets. Vitamin D, acarbose, and myoinositol are just a few of the reciprocal and optional clinical treatments that have been proved to be useful in the treatment of PCOS. The number of viable methods for dealing with PCOS-related infertility has increased as well. Despite the fact that clomiphene citrate (CC) has long been the gold standard for ovulation induction in the event of ovulatory infertility, aromatase inhibitors can induce ovulation with results that are nearly identical to or better than those reported with CC, aromatase inhibitors can cause ovulation with results that are nearly identical to or better than those reported with CC. Ovarian incitement conventions that intelligently utilize gonadotropins, gonadotropin-delivering hormone rivals, the approach of ovarian boring, and assisted conceptive advancements with in vitro oocyte development indicate an expanding level of therapeutic progress.

Polycystic ovary syndrome and reproductive health of women: a curious association.

Reproductive health is a broad concept that encompasses mortality, morbidity, and quality of life associated with the reproductive system, mechanism, and incidents encountered at all ages by men and women. Orthodox Indian society finds the conversation on reproductive health to be a taboo and discourages open conversations about it. Polycystic ovary syndrome (PCOS) is a reproductive-age metabolic endocrine disorder found in females. Females suffering from PCOS are prone to reproductive, metabolic, and cardiovascular disorders. In this paper, we will systematically review about effect of PCOS on Reproductive Health of Women. The numerous electronic databases such as: BMJ, LANCET, PUBMED, Unicef Website, WHO Website and Google Scholar have been comprehensively searched for studies linked to PCOS, its various effects and effect on women's reproductive health. For additional analyses, we have reviewed reference lists of reviews and collected papers. The effects of PCOS on women's reproductive health have been verified by several scientific reports worldwide. PCOS is a hormonal condition, as per multiple reports, with the ability to lead to different outcomes. It still appears to be a common cause among females of infertility. An integral aspect of the treatment of this disease is the early diagnosis of long-term morbidities by effective screening tests. In the future, studies must concentrate on the missing holes in our growing perception of this disease. Several studies have confirmed that reproductive morbidity, including irregular uterine bleeding, abortion, miscarriage, and other risk of pregnancy during reproductive years, is associated with PCOS. PCOS is an amalgam of physiological and psychosocial dysfunction, not just an endocrine disorder.

Unravelling the potency of triazole analogues for inhibiting α-synuclein fibrillogenesis and in vitro disaggregation.

A series of triazole-based compounds was synthesized using a click chemistry approach and evaluated for the inhibition of α-synuclein (α-syn) fibrillogenesis and its disaggregation. Compounds Tr3, Tr7, Tr12, Tr15, and Tr16 exhibited good effect in inhibiting α-syn fibrillogenesis confirmed by Thioflavin-T assay and fluorescence microscopy and α-syn disaggregation confirmed by fluorescence microscopy. Molecular docking was used to understand the plausible mechanism of the test compounds for inhibiting the α-syn fibrillogenesis and to verify the in vitro results. Compounds Tr3, Tr7, Tr12, Tr15 and Tr16 showed good binding interactions with the essential amino acid residues of α-syn. The compounds which were found to be good inhibitors or disaggregators had no toxic effects on the SH-SY5Y cell line. These compounds have the potential to be developed as therapeutic interventions against synucleinopathies including Parkinson's disease and Lewy body dementia.

Quinoline carboxamide core moiety-based compounds inhibit P. falciparumfalcipain-2: Design, synthesis and antimalarial efficacy studies.

Targeting Falcipain-2 (FP2) for the development of antimalarials is a promising and established concept in antimalarial drug discovery and development. FP2, a member of papain-family cysteine protease of the malaria parasite Plasmodium falciparum holds an important role in hemoglobin degradation pathway. A new series of quinoline carboxamide-based compounds was designed, synthesized and evaluated for antimalarial activity. We integrated molecular hybridization strategy with in-silico drug design to develop FP2 inhibitors. In-vitro results of FP2 inhibition by Qs17, Qs18, Qs20 and Qs21 were found to be in low micromolar range with IC50 4.78, 7.37, 2.14 and 2.64 µM, respectively. Among the 25 synthesized compounds, four compounds showed significant antimalarial activities. These compounds also depicted morphological and food-vacuole abnormalities much better than that of E-64, an established FP2 inhibitor. Overall these aromatic substituted quinoline carboxamides can serve as promising leads for the development of novel antimalarial agents.

Diphenyl triazine hybrids inhibit α-synuclein fibrillogenesis: Design, synthesis and in vitro efficacy studies.

Aggregation of α-synuclein (α-syn) is one of the central hypotheses for Parkinson's disease (PD), therefore, its inhibition and disaggregation is an optimistic approach for the treatment of PD. Here, we report design, synthesis and in-vitro efficacy studies of a series of diphenyl triazine hybrids as potential inhibitors of α-syn fibrillogenesis. From the docking studies, we concluded that compounds A1, A2, A4, A8 and A9 display promising binding affinity with the essential residues of α-syn with binding energy values: -6.0, -7.0, -6.3, -6.6 and -6.7 kcal/mol respectively. The target compounds were synthesized using multistep organic synthesis reactions. Compounds A1, A2 A4, A8 and A9 showed a significant lowering of the α-syn fibril formation during Thioflavin-T assay and fluorescence microscopy. In addition, these compounds A1, A2, A4, A8 and A9 also proved to be good disaggregators in the pre-aggregated form of α-syn. Most of the compounds exhibited no cytotoxicity in mouse embryonic fibroblast (MEF) and human adenocarcinomic alveolar basal epithelial cells (A549) except A2. Overall, diphenyl triazine-based compounds can be further investigated for the treatment of synucleinopathies and for Lewy body dementia in which α-syn is predominantly observed.

GSK3 Inhibitors in the Therapeutic Development of Diabetes, Cancer and Neurodegeneration: Past, Present and Future.

GSK3 has gained a considerable attention of researchers in the late 1970s as an inevitable drug target to treat diabetes. Furthermore, it was found to have a key role in the development of diseases like cancer and neurodegeneration (ND). A broad spectrum of GSK3 inhibitors have been discovered from time to time in order to curb these diseases. Inhibition of GSK3 by insulin boosts the dephosphorylation of glycogen synthase, hence its activation to convert UDP glucose into glycogen. Lack of insulin and insulin-resistance is supposed to be the cause of type 2 diabetes (Diabetes mellitus). Additionally, GSK3 stabilizes the components of beta-catenin complex, hence promotes oncogenesis. Phosphorylation of GSK3 by Akt and some other kinases also favours the carcinogenesis. However, in some cases GSK3 has tumor supressing character. GSK3 has been found to have a prominent role in the formation of amyloid plaques and neurofibrillary tangles (abnormal protein accumulations) which are the main suspects of Alzheimer's disease (AD). GSK3 inhibitors have been reported to have amyloidbeta disaggregation property and have been found to promote the adult hippocampal neurogenesis in vivo as well as in vitro. This manuscript thoroughly reviews the involvement of GSK3 in diabetes, cancer and ND. Furthermore, development of GSK3 inhibitors as antidiabetes, anticancer and antineurodegenerative agents focusing mainly on lead optimization has been discussed.

Dihydroorotate dehydrogenase: A drug target for the development of antimalarials.

Malaria is a critical human disease with extensive exploration yet unestablished due to occurrence of frequent drug resistance. This aspect of malaria pharmacology calls for the introduction of new antimalarial. The drugs reported till date targeted different stages of the parasites in order to stop their growth and proliferation. Beside this, various drugs that could inhibit the imperative enzymes of the parasite have also been reported. Amid them, dihydroorotate dehydrogenase (DHODH) has a key worth. DHODH is involved in the de novo pyrimidine biosynthesis of the malarial parasite which acts as a primary source of energy for its survival. Since life of the parasite utterly depends on pyrimidine biosynthesis, so it can be used as an apt drug target for malaria eradication. In addition to this, DHODH is also present in human and their active sites have significant structural dissimilarities, so the development of selective inhibitors may prove to be a milestone in search of new antimalarials. Inhibitors of human DHODH have been used to treat autoimmune diseases such as, rheumatoid arthritis or multiple sclerosis and have been investigated in the treatment of cancer, viral diseases, as well as in plant pathology. Here, we have reviewed the important role of DHODH as a viable drug target against malaria, its importance for the survival of the parasite, and DHODH inhibitors reported so far. The rate of success of the reported DHODH inhibitors and further required improvements have also been accounted.

Synthesis and screening of triazolopyrimidine scaffold as multi-functional agents for Alzheimer's disease therapies.

In present study a series of triazolopyrimidine-quinoline and cyanopyridine-quinoline hybrids were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs). Molecular docking and scoring was utilized for the design of inhibitors. The molecules were synthesized via an easily accessible, convergent synthetic route. Three triazolopyrimidine based compounds showed nanomolar activity towards acetylcholinesterase. Among them, Ethyl 6-fluoro-4-(4-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)piperazin-1-yl)quinoline-3-carboxylate (10d), strongly inhibited AChE with IC50 value of 42 nM. Furthermore compound 10d was identified as most promising compound with 12 fold selectivity against butyrylcholinesterase (BuChE). This compound displayed a composed multitargeted profile with promising inhibition of self-induced and AChE - induced Aß aggregation and antioxidant activity.

Pivotal role of glycogen synthase kinase-3: A therapeutic target for Alzheimer's disease.

Neurodegenerative diseases are among the most challenging diseases with poorly known mechanism of cause and paucity of complete cure. Out of all the neurodegenerative diseases, Alzheimer's disease is the most devastating and loosening of thinking and judging ability disease that occurs in the old age people. Many hypotheses came forth in order to explain its causes. In this review, we have enlightened Glycogen Synthase Kinase-3 which has been considered as a concrete cause for Alzheimer's disease. Plaques and Tangles (abnormal structures) are the basic suspects in damaging and killing of nerve cells wherein Glycogen Synthase Kinase-3 has a key role in the formation of these fatal accumulations. Various Glycogen Synthase Kinase-3 inhibitors have been reported to reduce the amount of amyloid-beta as well as the tau hyperphosphorylation in both neuronal and nonneuronal cells. Additionally, Glycogen Synthase Kinase-3 inhibitors have been reported to enhance the adult hippocampal neurogenesis in vivo as well as in vitro. Keeping the chemotype of the reported Glycogen Synthase Kinase-3 inhibitors in consideration, they may be grouped into natural inhibitors, inorganic metal ions, organo-synthetic, and peptide like inhibitors. On the basis of their mode of binding to the constituent enzyme, they may also be grouped as ATP, nonATP, and allosteric binding sites competitive inhibitors. ATP competitive inhibitors were known earlier inhibitors but they lack efficient selectivity. This led to find the new ways for the enzyme inhibition.