In 1984, Rosen and Scott1 first described cystic hypersecretory breast lesions. This entity has a spectrum of histologically distinct lesions ranging from cystic hypersecretory hyperplasia (CHH), CHH ...with atypia, cystic hypersecretory carcinoma (CHC) in situ, and invasive CHC. CHH’s macroscopic examination is distinct, which shows numerous cysts of varying sizes containing gelatinous material. The cyst lining epithelium, in CHH, consists of a single layer of flattened, columnar, or cuboidal epithelium without cytological atypia. Atypical CHH shows epithelial crowding, enlarged nuclei with loss of nuclear polarity, nuclear hyperchromasia, and mitoses. The in-situ carcinoma shows intermediate to high nuclear-grade lesions with micropapillary architecture.2 Most reported cases are of in-situ CHC. Invasive CHC shows solid nests of poorly differentiated cells with no secretory characteristics.3 This rare breast cancer subtype is not included in the 5th edition of the WHO breast tumor classification. The figure above shows the macro and microscopic examination of a lesion from a 58-year-old lady who presented with a lump in her right breast for six months. Imaging revealed a large solid tumor in the upper inner quadrant of the breast. A right mastectomy was performed for this patient. On gross inspection, the skin and nipple areola complex were unremarkable. The cut surface of the breast showed two different lesions. The first was a large, solid, well-demarcated whitish mass of 8.5x6.5x4.0 cm (Figure 1A). Additionally, an ill-defined lesion was identified in the adjacent breast parenchyma composed of clusters of multiple variable-sized yellowish nodules, ranging in size from few millimetres to 1.0 cm (Figure 1B). Figure 1A – gross examination from the first lesion reveals large, well-defined solid, greyish white firm tumour of 8.5x6.5x4.0 cm (scale bar= 3 cm); B – gross examination from the second lesion shows multiple variable-sized yellowish-white nodules of 1.0 mm to 10.0 mm (scale bar 1 cm); C – photomicrograph from the solid tumour shows a cellular invasive tumour arranged in solid trabecular and sheet-like architecture with marked nuclear anaplasia and focal necrosis (H&E 100X); D – photomicrograph from the second lesion shows multiple cystically dilated spaces lined by cuboidal epithelium and filled with homogeneous eosinophilic colloid-like material with few macrophages, indicating CHH (H&E, 40X); E – photomicrograph shows CHH with nuclear atypia and epithelial multilayering (H&E 400X).: The microscopic examination of the large solid mass showed a high-grade pleomorphic invasive tumor arranged in sheets and trabeculae of cells with marked nuclear pleomorphism (Figure 1C). Mitotic figures were frequent, and a focal area of necrosis was also identified. However, no microcystic or secretory changes could be identified even on examining multiple sections. Microscopic examination from the ill-defined nodular lesions showed numerous dilated cysts lined by cuboidal to columnar epithelial cells containing colloid-like eosinophilic cyst content admixed with a few foamy macrophages (Figure 1D). Occasional cysts showed nuclear atypia and epithelial multilayering (Figure 1E). However, definite in-situ carcinoma was not detected. IHC for hormone markers revealed ER and PR negative status with strong, complete membranous Her-2-neu expression in the tumor cells. Given the high-grade pleomorphic solid tumor con-existing with CHH and CHH with atypia, the invasive tumor was diagnosed as CHC. The diagnosis of CHH can be challenging on FNA and core needle biopsy specimens. Lesions like juvenile papillomatosis, fibrocystic change, columnar cell change with or without atypia, extravasation mucocele, mucinous carcinoma, secretory carcinoma, ‘clinging’ type DCIS, and metastatic thyroid carcinoma can mimic the morphology of CHH.4 Although CHH is considered a benign lesion, malignant transformation on long-term follow-up has been reported.2 Also, there is a chance of having an in-situ or high-grade invasive tumor component with CHH. Hence, a diagnosis of CHH should alert the physician about possible association with malignancy, and a wide local excision followed by thorough sampling should be performed to look for any invasive tumor.5 In conclusion, cystic hypersecretory lesions rarely encountered entities with a wide spectrum of lesions, from benign to overtly malignant. Pathologists should be well versed in the gross and microscopic features and consider the possible diagnostic pitfalls while dealing with this tumor. Although cystic hypersecretory carcinoma is not identified as a separate entity in the WHO 5th edition of breast tumor classification, associated CHH in the surrounding parenchyma indicates the invasive tumor as an invasive CHC. The available literature is limited; however, most cases of invasive CHC are high-grade solid tumors, as encountered in this case.
Heavy metals are well-known environmental pollutants owing to their toxicity, longevity in the atmosphere, and ability to accumulate in the human body via bioaccumulation. The pollution of ...terrestrial and aquatic ecosystems with toxic heavy metals is a major environmental concern that has consequences for public health. Most heavy metals occur naturally, but a few are derived from anthropogenic sources. Heavy metals are characterized by their high atomic mass and toxicity to living organisms. Most heavy metals cause environmental and atmospheric pollution, and may be lethal to humans. Heavy metals can become strongly toxic by mixing with different environmental elements, such as water, soil, and air, and humans and other living organisms can be exposed to them through the food chain. Plenty of experimental studies were performed to appraise the promising treatment options from natural products. Additionally, nanotechnology based treatment options are being constantly developed. As an emerging field, nanotechnology is making substantial advances in the analysis and removal of heavy metals from complicated matrices. Removal of heavy metal has been accomplished by the use of a variety of nanomaterials, including graphene and its derivatives, magnetic nanoparticles, metal oxide nanoparticles, and carbon nanotubes, to name a few. Using nanotechnology for heavy metal analysis and removal from food and water resources provides many benefits over traditional methods. These advantages include a broad linear range, low detection and quantification limits, a high sensitivity, and high selectivity. Therefore this review aimed to explore the environmental consequences of the heavy metals, toxicity to the human health, as well as novel therapeutics development from the natural resources. Additionally, nanotechnological and nanomedicinal applications to treat heavy metal toxicity are also highlighted in this review.
The field of nanotechnology is concerned with the creation and application of materials having a nanoscale spatial dimensioning. Having a considerable surface area to volume ratio, nanoparticles have ...particularly unique properties. Several chemical and physical strategies have been used to prepare zinc oxide nanoparticles (ZnO-NPs). Still, biological methods using green or natural routes in various underlying substances (e.g., plant extracts, enzymes, and microorganisms) can be more environmentally friendly and cost-effective than chemical and/or physical methods in the long run. ZnO-NPs are now being studied as antibacterial agents in nanoscale and microscale formulations. The purpose of this study is to analyze the prevalent traditional method of generating ZnO-NPs, as well as its harmful side effects, and how it might be addressed utilizing an eco-friendly green approach. The study's primary focus is on the potential biomedical applications of green synthesized ZnO-NPs. Biocompatibility and biomedical qualities have been improved in green-synthesized ZnO-NPs over their traditionally produced counterparts, making them excellent antibacterial and cancer-fighting drugs. Additionally, these ZnO-NPs are beneficial when combined with the healing processes of wounds and biosensing components to trace small portions of biomarkers linked with various disorders. It has also been discovered that ZnO-NPs can distribute and sense drugs. Green-synthesized ZnO-NPs are compared to traditionally synthesized ones in this review, which shows that they have outstanding potential as a potent biological agent, as well as related hazardous properties.
Antibiotics have been used to cure bacterial infections for more than 70 years, and these low-molecular-weight bioactive agents have also been used for a variety of other medicinal applications. In ...the battle against microbes, antibiotics have certainly been a blessing to human civilization by saving millions of lives. Globally, infections caused by multidrug-resistant (MDR) bacteria are on the rise. Antibiotics are being used to combat diversified bacterial infections. Synthetic biology techniques, in combination with molecular, functional genomic, and metagenomic studies of bacteria, plants, and even marine invertebrates are aimed at unlocking the world's natural products faster than previous methods of antibiotic discovery. There are currently only few viable remedies, potential preventive techniques, and a limited number of antibiotics, thereby necessitating the discovery of innovative medicinal approaches and antimicrobial therapies. MDR is also facilitated by biofilms, which makes infection control more complex. In this review, we have spotlighted comprehensively various aspects of antibiotics viz. overview of antibiotics era, mode of actions of antibiotics, development and mechanisms of antibiotic resistance in bacteria, and future strategies to fight the emerging antimicrobial resistant threat.
Plant-based phytochemicals are now being used to treat plenty of physiological diseases. Herbal drugs have gained popularity in recent years because of their strength, purity, and cheap ...cost-effectiveness. Citrus fruits contain significant amounts of flavanones, which falls to the category of polyphenols. Flavanones occupy a major fraction of the total polyphenols present in the plasma when orange juice is taken highly or in moderate states. Narirutin is a disaccharide derivative available in citrus fruits, primarily dihydroxy flavanone. From a pharmacological viewpoint, narirutin is a bioactive phytochemical with therapeutic efficacy. Many experimental researches were published on the use of narirutin. Anticancer activity, neuroprotection, stress relief, hepatoprotection, anti-allergic activity, antidiabetic activity, anti-adipogenic activity, anti-obesity action, and immunomodulation are a couple of the primary pharmacological properties. Narirutin also has antioxidant, and anti-inflammatory activities. The ultimate goal of this review is to provide the current scenario of pharmacological research with narirutin; to make a better understanding for therapeutic potential of narirutin, as well as its biosynthesis strategies and side effects. Extensive literature searches and studies were undertaken to determine the pharmacological properties of narirutin.
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•Flavanones are polyphenolic compounds found high concentrations in citrus fruits.•Narirutin is a disaccharide derivative highly available in citrus fruits.•Narirutin processed a variety of pharmacological activities.•This review described the pharmacological activities of narirutin.
Berberine (BBR), a potential bioactive agent, has remarkable health benefits. A substantial amount of research has been conducted to date to establish the anticancer potential of BBR. The present ...review consolidates salient information concerning the promising anticancer activity of this compound. The therapeutic efficacy of BBR has been reported in several studies regarding colon, breast, pancreatic, liver, oral, bone, cutaneous, prostate, intestine, and thyroid cancers. BBR prevents cancer cell proliferation by inducing apoptosis and controlling the cell cycle as well as autophagy. BBR also hinders tumor cell invasion and metastasis by down-regulating metastasis-related proteins. Moreover, BBR is also beneficial in the early stages of cancer development by lowering epithelial-mesenchymal transition protein expression. Despite its significance as a potentially promising drug candidate, there are currently no pure berberine preparations approved to treat specific ailments. Hence, this review highlights our current comprehensive knowledge of sources, extraction methods, pharmacokinetic, and pharmacodynamic profiles of berberine, as well as the proposed mechanisms of action associated with its anticancer potential. The information presented here will help provide a baseline for researchers, scientists, and drug developers regarding the use of berberine as a promising candidate in treating different types of cancers.
Cancer is one of the leading causes of death worldwide. Several treatments are available for cancer treatment, but many treatment methods are ineffective against multidrug-resistant cancer. Multidrug ...resistance (MDR) represents a major obstacle to effective therapeutic interventions against cancer. This review describes the known MDR mechanisms in cancer cells and discusses ongoing laboratory approaches and novel therapeutic strategies that aim to inhibit, circumvent, or reverse MDR development in various cancer types. In this review, we discuss both intrinsic and acquired drug resistance, in addition to highlighting hypoxia- and autophagy-mediated drug resistance mechanisms. Several factors, including individual genetic differences, such as mutations, altered epigenetics, enhanced drug efflux, cell death inhibition, and various other molecular and cellular mechanisms, are responsible for the development of resistance against anticancer agents. Drug resistance can also depend on cellular autophagic and hypoxic status. The expression of drug-resistant genes and the regulatory mechanisms that determine drug resistance are also discussed. Methods to circumvent MDR, including immunoprevention, the use of microparticles and nanomedicine might result in better strategies for fighting cancer.
Since the start of the COVID-19 pandemic, numerous variants of SARS-CoV-2 have been reported worldwide. The advent of variants of concern (VOCs) raises severe concerns amid the serious containment ...efforts against COVID-19 that include physical measures, pharmacological repurposing, immunization, and genomic/community surveillance. Omicron variant (B.1.1.529) has been identified as a highly modified, contagious, and crucial variant among the five VOCs of SARS-CoV-2. The increased affinity of the spike protein (S-protein), and host receptor, angiotensin converting enzyme-2 (ACE-2), due to a higher number of mutations in the receptor-binding domain (RBD) of the S-protein has been proposed as the primary reason for the decreased efficacy of majorly available vaccines against the Omicron variant and the increased transmissible nature of the Omicron variant. Because of its significant competitive advantage, the Omicron variant and its sublineages swiftly surpassed other variants to become the dominant circulating lineages in a number of nations. The Omicron variant has been identified as a prevalent strain in the United Kingdom and South Africa. Furthermore, the emergence of recombinant variants through the conjunction of the Omicron variant with other variants or by the mixing of the Omicron variant's sublineages/subvariants poses a major threat to humanity. This raises various issues and hazards regarding the Omicron variant and its sublineages, such as an Omicron variant breakout in susceptible populations among fully vaccinated persons. As a result, understanding the features and genetic implications of this variant is crucial. Hence, we explained in depth the evolution and features of the Omicron variant and analyzed the repercussions of spike mutations on infectiousness, dissemination ability, viral entry mechanism, and immune evasion. We also presented a viewpoint on feasible strategies for precluding and counteracting any future catastrophic emergence and spread of the omicron variant and its sublineages that could result in a detrimental wave of COVID-19 cases.
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•The emergence of the Omicron variant and its sublineages pose a severe threat.•Significant number of mutations in the Omicron variant has been associated.•The Omicron variant might have evolved separately from all the previous variants.•Omicron and other variants may generate resistant variants to present vaccines.•Genomic surveillance and Omicron-specific vaccines are containment measures.
Obesity and diabetes are the most demanding health problems today, and their prevalence, as well as comorbidities, is on the rise all over the world. As time goes on, both are becoming big issues ...that have a big impact on people's lives. Diabetes is a metabolic and endocrine illness set apart by hyperglycemia and glucose narrow-mindedness because of insulin opposition. Heftiness is a typical, complex, and developing overall wellbeing worry that has for quite some time been connected to significant medical issues in individuals, all things considered. Because of the wide variety and low adverse effects, herbal products are an important hotspot for drug development. Synthetic compounds are not structurally diverse and lack drug-likeness properties. Thus, it is basic to keep on exploring herbal products as possible wellsprings of novel drugs. We conducted this review of the literature by searching Scopus, Science Direct, Elsevier, PubMed, and Web of Science databases. From 1990 until October 2021, research reports, review articles, and original research articles in English are presented. It provides top to bottom data and an examination of plant-inferred compounds that might be utilized against heftiness or potentially hostile to diabetes treatments. Our expanded comprehension of the systems of activity of phytogenic compounds, as an extra examination, could prompt the advancement of remedial methodologies for metabolic diseases. In clinical trials, a huge number of these food kinds or restorative plants, as well as their bioactive compounds, have been shown to be beneficial in the treatment of obesity.
Emodin is an anthraquinone derivative found in the roots and bark of a variety of plants, molds, and lichens. Emodin has been used as a traditional medication for more than 2000 years and is still ...common in numerous herbal drugs. Emodin is plentiful in the three plant families, including Polygonaceae (Rheum, Rumex, and Polygonum spp.), Fabaceae (Cassia spp.), and Rhamnaceae (Rhamnus, Frangula, and Ventilago spp.). Emerging experimental evidences indicate that emodin confers a wide range of pharmacological activities; special focus was implemented toward neurodegenerative diseases, including Alzheimer's disease, Parkinson’s disease, cerebral ischemia, anxiety and depression, schizophrenia, chronic hyperglycemic peripheral neuropathy, etc. Numerous preclinical evidences were established in support of the neuroprotection of emodin. However, this review highlighted the role of emodin as a potent neurotherapeutic agent; therefore, its evidence-based functionality on neurological disorders (NDs).
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1.Emodin confers a wide range of neuropharmacological activities.2.Preclinical evidences were established to support emodin's neuroprotection.3.Botanical sources and chemistry of emodin are discussed.4.Toxicity and biosafety profile of emodin are also highlighted.
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