Multimodal epigenetic sequencing analysis (MESA) of cell-free DNA for non-invasive colorectal cancer detection.

BACKGROUND: Detecting human cancers through cell-free DNA (cfDNA) in blood is a sensitive and non-invasive option. However, capturing multiple forms of epigenetic information remains a technical and financial challenge. METHODS: To address this, we developed multimodal epigenetic sequencing analysis (MESA), a flexible and sensitive approach to capturing and integrating a diverse range of epigenetic features in cfDNA using a single experimental assay, i.e., non-disruptive bisulfite-free methylation sequencing, such as Enzymatic Methyl-seq. MESA enables simultaneous inference of four epigenetic modalities: cfDNA methylation, nucleosome occupancy, nucleosome fuzziness, and windowed protection score for regions surrounding gene promoters and polyadenylation sites. RESULTS: When applied to 690 cfDNA samples from 3 colorectal cancer clinical cohorts, MESA's novel modalities, which include nucleosome fuzziness, and genomic features, including polyadenylation sites, improve cancer detection beyond the traditional epigenetic markers of promoter DNA methylation. CONCLUSIONS: Together, MESA stands as a major advancement in the field by utilizing comprehensive and complementary epigenetic profiles of cfDNA for effective non-invasive cancer detection.

Neighborhood deprivation and morbid obesity: Insights from the Houston Methodist Cardiovascular Disease Health System Learning Registry.

This study examined the relationship between a validated measure of socioeconomic deprivation, such as the Area Deprivation Index (ADI), and morbid obesity. We used cross-sectional data on adult patients (≥18 years) in the Houston Methodist Cardiovascular Disease Health System Learning Registry (located in Houston, Texas, USA) between June 2016 and July 2021. Each patient was grouped by quintiles of ADI, with higher quintiles signaling greater deprivation. BMI was calculated using measured height and weight with morbid obesity defined as ≥ 40 kg/m2. Multivariable logistic regression models were used to examine the association between ADI and morbid obesity adjusting for demographic (age, sex, and race/ethnicity) factors. Out of the 751,174 adults with an ADI ranking included in the analysis, 6.9 % had morbid obesity (n = 51,609). Patients in the highest ADI quintile had a higher age-adjusted prevalence (10.9 % vs 3.3 %), and about 4-fold odds (aOR, 3.8; 95 % CI = 3.6, 3.9) of morbid obesity compared to the lowest ADI quintile. We tested for and found interaction effects between ADI and each demographic factor, with stronger ADI-morbid obesity association observed for patients that were female, Hispanic, non-Hispanic White and 40-65 years old. The highest ADI quintile also had a high prevalence (44 %) of any obesity (aOR, 2.2; 95 % CI = 2.1, 2.2). In geospatial mapping, areas with higher ADI were more likely to have higher proportion of patients with morbid obesity. Census-based measures, like the ADI, may be informative for area-level obesity reduction strategies as it can help identify neighborhoods at high odds of having patients with morbid obesity.

Common postoperative complications after general anesthesia in oral and maxillofacial surgery.

AIM AND OBJECTIVES: Anesthesia is Greek word meaning loss of sensation, and involves painful invasive procedure to be performed with little distress and no pain to the patient. Postoperative anesthetic complications are very common and duration of surgery is frequently cited as major risk factor for postoperative complications. The recognition and treatment of these complications are important when providing good quality care. The purpose of this study was to evaluate mild, moderate, and severe postoperative complications in patients undergoing maxillofacial surgery under general anesthesia and also determine the safety of general anesthesia in healthy and patients with comorbidities. SUBJECTS AND METHODS: This prospective study was conducted in the oral and maxillofacial surgery department. Two hundred and twenty patients who were operated under general anesthesia were taken in study. All relevant past medical and dental records were noted and were supported by preformulated questionnaire and was filled preoperatively and after surgery to 12 weeks. RESULTS: Mild-to-moderate and severe complications were noted. Females showed more complications than males. Most common complications were sore throat, dysphagia, nausea, vomiting, pain, swelling in normal patients, and in patients with comorbidities delayed wound healing, hypertension, and infection were also seen. CONCLUSION: The use of General Anesthesia is considered safe but it has few risks associated with it and past medical conditions should be evaluated preoperatively.

Impact of a standardized reporting format on the quality of MRI reports for rectal cancer staging.

BACKGROUND AND AIMS: Besides providing a surgical roadmap, rectal MRI plays a major role in treatment planning. We recently started using a structured template for reporting rectal cancer via MRI. We study the impact of using this template at our hospital in terms of number of essential imaging parameters described in the reports as compared to the pre-template free-text reports. METHODS: A structured rectal MRI reporting template was created in consensus with members of the colorectal tumour board and was introduced in the department, which included 14 essential parameters to be mentioned in the reports. We conducted a retrospective analysis of rectal MRI reports of 100 cases with histologically proven rectal cancer, comprising 50 consecutive free-text reports before the template was introduced and 50 consecutive structured reports after its introduction, checking for the presence or absence of inclusion of the 14 parameters. An anonymous online feedback survey was conducted as well after the introduction of the template for the members of the colorectal tumour board. RESULTS: Overall, the total number of parameters reported increased from a median value of 10 (range 6-13) to 14 (range 12-14). The common unreported parameters prior to template introduction included T staging, presence or absence of restricted diffusion, anterior peritoneal reflection (APR) involvement, and presence or absence of extramural vascular invasion; these were reported in 16%, 22%, 30% and 50% respectively. These improved to 98-100% reporting after template introduction. Maximum improvement was in T staging (16% to 98%) (P < 0.0001), restricted diffusion on DWI (from 22% to 100%) (P < 0.0001) and APR involvement (from 30% to 100%) (P < 0.0001). The most common unreported parameter after template introduction was the "tumoral T2 signal intensity" (unreported in 4% cases). The results of the survey were as follows: 100% felt a decreased need to talk to the radiologist to clarify the report, 81.8% felt an improvement in the quality of reporting as compared to free style reports, and 91% felt that the new template is easier to interpret. CONCLUSION: The introduction of a structured template for rectal cancer significantly improved the quality of rectal MRI reports, along with the satisfaction of referring providers.

Massive gene amplification on a recently formed Drosophila Y chromosome.

Widespread loss of genes on the Y is considered a hallmark of sex chromosome differentiation. Here we show that the initial stages of Y evolution are driven by massive amplification of distinct classes of genes. The neo-Y chromosome of Drosophila miranda initially contained about 3,000 protein-coding genes, but has gained over 3,200 genes since its formation about 1.5 million years ago primarily by tandem amplification of protein-coding genes ancestrally present on this chromosome. We show that distinct evolutionary processes may account for this drastic increase in gene number on the Y. Testis-specific and dosage-sensitive genes appear to have amplified on the Y to increase male fitness. A distinct class of meiosis-related multi-copy Y genes independently co-amplified on the X, and their expansion is probably driven by conflicts over segregation. Co-amplified X/Y genes are highly expressed in testis, enriched for meiosis and RNA interference functions and are frequently targeted by small RNAs in testis. This suggests that their amplification is driven by X versus Y antagonism for increased transmission, where sex chromosome drive suppression is probably mediated by sequence homology between the suppressor and distorter through the RNA interference mechanism. Thus, our analysis suggests that newly emerged sex chromosomes are a battleground for sexual and meiotic conflict.

The Continuing Evolution of Molecular Functional Imaging in Clinical Oncology: The Road to Precision Medicine and Radiogenomics (Part I).

The present era of precision medicine sees 'cancer' as a consequence of molecular derangements occurring at the commencement of the disease process, with morphologic changes happening much later in the process of tumorigenesis. Conventional imaging techniques, such as computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI), play an integral role in the detection of disease at a macroscopic level. However, molecular functional imaging (MFI) techniques entail the visualisation and quantification of biochemical and physiological processes occurring during tumorigenesis, and thus has the potential to play a key role in heralding the transition from the concept of 'one size fits all' to 'precision medicine'. Integration of MFI with other fields of tumour biology such as genomics has spawned a novel concept called 'radiogenomics', which could serve as an indispensable tool in translational cancer research. With recent advances in medical image processing, such as texture analysis, deep learning, and artificial intelligence (AI), the future seems promising; however, their clinical utility remains unproven at present. Despite the emergence of novel imaging biomarkers, a majority of these require validation before clinical translation is possible. In this two-part review, we discuss the systematic collaboration across structural, anatomical, and molecular imaging techniques that constitute MFI. Part I reviews positron emission tomography, radiogenomics, AI, and optical imaging, while part II reviews MRI, CT and ultrasound, their current status, and recent advances in the field of precision oncology.

The Continuing Evolution of Molecular Functional Imaging in Clinical Oncology: The Road to Precision Medicine and Radiogenomics (Part II).

The present era of precision medicine sees "cancer" as a consequence of molecular derangements occurring at the commencement of the disease process, with morphological changes happening much later in the process of tumourigenesis. Conventional imaging techniques, such as computed tomography (CT), ultrasound (US) and magnetic resonance imaging (MRI) play an integral role in the detection of disease at the macroscopic level. However, molecular functional imaging (MFI) techniques entail the visualisation and quantification of biochemical and physiological processes occurring during tumourigenesis. MFI has the potential to play a key role in heralding the transition from the concept of "one-size-fits-all" treatment to "precision medicine". Integration of MFI with other fields of tumour biology such as genomics has spawned a novel concept called "radiogenomics", which could serve as an indispensable tool in translational cancer research. With recent advances in medical image processing, such as texture analysis, deep learning and artificial intelligence, the future seems promising; however, their clinical utility remains unproven at present. Despite the emergence of novel imaging biomarkers, the majority of these require validation before clinical translation is possible. In this two part review, we discuss the systematic collaboration across structural, anatomical and molecular imaging techniques that constitute MFI. Part I reviews positron emission tomography, radiogenomics, AI, and optical imaging, while part II reviews MRI, CT and ultrasound, their current status, and recent advances in the field of precision oncology.

Correction to: The Continuing Evolution of Molecular Functional Imaging in Clinical Oncology: The Road to Precision Medicine and Radiogenomics (Part II).

An Online First version of this article was made available online at http://link.springer.com/journal/40291/onlineFirst/page/1 on 01 Nov 2018. An error was subsequently identified in the article, and the following correction should be noted.

De novo assembly of a young Drosophila Y chromosome using single-molecule sequencing and chromatin conformation capture.

While short-read sequencing technology has resulted in a sharp increase in the number of species with genome assemblies, these assemblies are typically highly fragmented. Repeats pose the largest challenge for reference genome assembly, and pericentromeric regions and the repeat-rich Y chromosome are typically ignored from sequencing projects. Here, we assemble the genome of Drosophila miranda using long reads for contig formation, chromatin interaction maps for scaffolding and short reads, and optical mapping and bacterial artificial chromosome (BAC) clone sequencing for consensus validation. Our assembly recovers entire chromosomes and contains large fractions of repetitive DNA, including about 41.5 Mb of pericentromeric and telomeric regions, and >100 Mb of the recently formed highly repetitive neo-Y chromosome. While Y chromosome evolution is typically characterized by global sequence loss and shrinkage, the neo-Y increased in size by almost 3-fold because of the accumulation of repetitive sequences. Our high-quality assembly allows us to reconstruct the chromosomal events that have led to the unusual sex chromosome karyotype in D. miranda, including the independent de novo formation of a pair of sex chromosomes at two distinct time points, or the reversion of a former Y chromosome to an autosome.

Design, Synthesis and Biological Evaluation of 7-arylbenzo[c]acridine-5,6- diones as Potential Anti-Leishmanial and anti-trypanosomal Agents.

BACKGROUND: Leishmaniasis is endemic in 98 countries and is closely associated with poverty. On the basis of current evidence, it may be safely suggested that over time Leishmania spp. have evolved coexistence in different macrophage types and developed adaptations in order to ensure their intracellular survival. Considering new drugs, the need of the hour the present study deals with the synthesis of novel compounds of biological importance based on naturally occurring scaffolds. OBJECTIVE: Synthesis, anti-leishmanial and anti-trypanosomal activities of a series of thirty three (eighteen newly synthesized and fifteen previously reported) 7-arylbenzo[c]acridine-5,6-diones. METHOD: A series of thirty-three 7-arylbenzo[c]acridine-5,6-diones was designed and synthesized. The anti-leishmanial and anti-trypanosomal activities of the newly synthesized compounds were done. RESULTS: Seven compounds (14, 17, 19, 26, 27, 38 and 39) were found to exhibit excellent antiparasitic activities. Compound 14 was identified as the most potent compound against L. donovani promastigotes while compound 27 showed most significant inhibition activity against amastigotes. Compounds 14 and 27 showed remarkable inhibitory activity with IC50 values of 0.38 and 0.53 µM, respectively, when tested in human macrophage cell line (THP) infected with L. donovani amastigotes. Against trypanomastigotes, six compounds (15, 17, 19, 25, 26 and 43) demonstrated remarkable inhibition. CONCLUSION: Compound 19 was found to be the best anti-trypanosomal agent and showed 300-fold superior inhibitory activity to that of the standard drug DFMO. Significant anti-leishmanial and anti-trypanosomal activities combined with the non-cytotoxic profile presents 7-arylbenzo[c]acridine- 5,6-diones as new candidates with therapeutic potential in the treatment of parasitic diseases.

Convergent evolution of Y chromosome gene content in flies.

Sex-chromosomes have formed repeatedly across Diptera from ordinary autosomes, and X-chromosomes mostly conserve their ancestral genes. Y-chromosomes are characterized by abundant gene-loss and an accumulation of repetitive DNA, yet the nature of the gene repertoire of fly Y-chromosomes is largely unknown. Here we trace gene-content evolution of Y-chromosomes across 22 Diptera species, using a subtraction pipeline that infers Y genes from male and female genome, and transcriptome data. Few genes remain on old Y-chromosomes, but the number of inferred Y-genes varies substantially between species. Young Y-chromosomes still show clear evidence of their autosomal origins, but most genes on old Y-chromosomes are not simply remnants of genes originally present on the proto-sex-chromosome that escaped degeneration, but instead were recruited secondarily from autosomes. Despite almost no overlap in Y-linked gene content in different species with independently formed sex-chromosomes, we find that Y-linked genes have evolved convergent gene functions associated with testis expression. Thus, male-specific selection appears as a dominant force shaping gene-content evolution of Y-chromosomes across fly species.While X-chromosome gene content tends to be conserved, Y-chromosome evolution is dynamic and difficult to reconstruct. Here, Mahajan and Bachtrog use a subtraction pipeline to identify Y-linked genes in 22 Diptera species, revealing patterns of Y-chromosome gene-content evolution.

Effect of listening to Vedic chants and Indian classical instrumental music on patients undergoing upper gastrointestinal endoscopy: A randomized control trial.

BACKGROUND: A high level of preoperative anxiety is common among patients undergoing medical and surgical procedures. Anxiety impacts of gastroenterological procedures on psychological and physiological responses are worth consideration. AIMS AND OBJECTIVES: To analyze the effect of listening to Vedic chants and Indian classical instrumental music on anxiety levels and on blood pressure (BP), heart rate (HR), and oxygen saturation in patients undergoing upper gastrointestinal (GI) endoscopy. MATERIALS AND METHODS: A prospective, randomized controlled trial was done on 199 patients undergoing upper GI endoscopy. On arrival, their anxiety levels were assessed using state and trait scores and various physiological parameters such as HR, BP, and SpO2. Patients were randomly divided into three groups: Group I of 67 patients who were made to listen prerecorded Vedic chants for 10 min, Group II consisting of 66 patients who listened to Indian classical instrumental music for 10 min, and Group III of 66 controls who remained seated for same period in the same environment. Thereafter, their anxiety state scores and physiological parameters were reassessed. RESULTS: A significant reduction in anxiety state scores was observed in the patients in Group I (from 40.4 ± 8.9 to 38.5 ± 10.7; P < 0.05) and Group II (from 41.8 ± 9.9 to 38.0 ± 8.6; P < 0.001) while Group III controls showed no significant change in the anxiety scores. A significant decrease in systolic BP (P < 0.001), diastolic BP (P < 0.05), and SpO2 (P < 0.05 was also observed in Group II. CONCLUSION: Listening to Vedic chants and Indian classical instrumental music has beneficial effects on alleviating anxiety levels induced by apprehension of invasive procedures and can be of therapeutic use.

Alternative Splicing within and between Drosophila Species, Sexes, Tissues, and Developmental Stages.

Alternative pre-mRNA splicing ("AS") greatly expands proteome diversity, but little is known about the evolutionary landscape of AS in Drosophila and how it differs between embryonic and adult stages or males and females. Here we study the transcriptomes from several tissues and developmental stages in males and females from four species across the Drosophila genus. We find that 20-37% of multi-exon genes are alternatively spliced. While males generally express a larger number of genes, AS is more prevalent in females, suggesting that the sexes adopt different expression strategies for their specialized function. While the number of total genes expressed increases during early embryonic development, the proportion of expressed genes that are alternatively spliced is highest in the very early embryo, before the onset of zygotic transcription. This indicates that females deposit a diversity of isoforms into the egg, consistent with abundant AS found in ovary. Cluster analysis by gene expression ("GE") levels shows mostly stage-specific clustering in embryonic samples, and tissue-specific clustering in adult tissues. Clustering embryonic stages and adult tissues based on AS profiles results in stronger species-specific clustering, suggesting that diversification of splicing contributes to lineage-specific evolution in Drosophila. Most sex-biased AS found in flies is due to AS in gonads, with little sex-specific splicing in somatic tissues.

Quantifying polymorphism and divergence from epigenetic data: a framework for inferring the action of selection.

Epigenetic modifications are alterations that regulate gene expression without modifying the underlying DNA sequence. DNA methylation and histone modifications, for example, are capable of spatial and temporal regulation of expression-with several studies demonstrating that these epigenetic marks are heritable. Thus, like DNA sequence, epigenetic marks are capable of storing information and passing it from one generation to the next. Because the epigenome is dynamic and epigenetic modifications can respond to external environmental stimuli, such changes may play an important role in adaptive evolution. While recent studies provide strong evidence for species-specific signatures of epigenetic marks, little is known about the mechanisms by which such modifications evolve. In order to address this question, we analyze the genome wide distribution of an epigenetic histone mark (H3K4me3) in prefrontal cortex neurons of humans, chimps and rhesus macaques. We develop a novel statistical framework to quantify within- and between-species variation in histone methylation patterns, using an ANOVA-based method and defining an FST -like measure for epigenetics (termed epi- FST), in order to develop a deeper understanding of the evolutionary pressures acting on epigenetic variation. Results demonstrate that genes with high epigenetic FST values are indeed significantly overrepresented among genes that are differentially expressed between species, and we observe only a weak correlation with SNP density.

Partial dosage compensation in Strepsiptera, a sister group of beetles.

Sex chromosomes have evolved independently in many different taxa, and so have mechanisms to compensate for expression differences on sex chromosomes in males and females. Different clades have evolved vastly different ways to achieve dosage compensation, including hypertranscription of the single X in male Drosophila, downregulation of both X's in XX Caenorhabditis, or inactivation of one X in female mammals. In the flour beetle Tribolium, the X appears hyperexpressed in both sexes, which might represent the first of two steps to evolve dosage compensation along the paths mammals may have taken (i.e., upregulation of X in both sexes, followed by inactivation of one X in females). Here we test for dosage compensation in Strepsiptera, a sister taxon to beetles. We identify sex-linked chromosomes in Xenos vesparum based on genomic analysis of males and females, and show that its sex chromosome consists of two chromosomal arms in Tribolium: The X chromosome that is shared between Tribolium and Strepsiptera, and another chromosome that is autosomal in Tribolium and another distantly related Strepsiptera species, but sex-linked in X. vesparum. We use RNA-seq (RNA sequencing) to show that dosage compensation along the X of X. vesparum is partial and heterogeneous. In particular, genes that are X-linked in both beetles and Strepsiptera appear fully dosage compensated probably through downregulation in both sexes, whereas genes on the more recently added X segment have evolved only partial dosage compensation. In addition, reanalysis of published RNA-seq data suggests that Tribolium has evolved dosage compensation, without hypertranscribing the X in females. Our results demonstrate that patterns of dosage compensation are highly variable across sex-determination systems and even within species.

Lingual thyroid in a young female: role of imaging.

A 12-year-old girl presented with dysphagia and a feeling of fullness in the throat. On examination a midline smooth, rubbery and reddish mass was seen at the base of the tongue, which moved with deglutination and protrusion of the tongue. A thyroid function test was within normal limits. On ultrasonography, absences of thyroid gland in its normal position with a smooth-contoured, round-shaped nodular mass at the tongue base with internal vascularity within. The mass was hyperdense and homogeneously enhancing on postcontrast. A clinical diagnosis of ectopic lingual was made based on the ultrasonography and CT scan features.

A one-pot, three-component reaction for the synthesis of novel 7-arylbenzo[c]acridine-5,6-diones.

A one pot domino protocol for an efficient synthesis of 7-arylbenzo[c]acridine-5,6-diones, with a novel nucleus, has been developed by reacting 2-hydroxynaphthalene-1,4-dione, aromatic aldehydes and aromatic amines using environmentally benevolent p-toluene sulphonic acid as a catalyst. An exciting feature of this communication is the reaction mechanism that depends on the reaction solvent.

The impact of equilibrium assumptions on tests of selection.

With the increasing availability and quality of whole genome population data, various methodologies of population genetic inference are being utilized in order to identify and quantify recent population-level selective events. Though there has been a great proliferation of such methodology, the type-I and type-II error rates of many proposed statistics have not been well-described. Moreover, the performance of these statistics is often not evaluated for different biologically relevant scenarios (e.g., population size change, population structure), nor for the effect of differing data sizes (i.e., genomic vs. sub-genomic). The absence of the above information makes it difficult to evaluate newly available statistics relative to one another, and thus, difficult to choose the proper toolset for a given empirical analysis. Thus, we here describe and compare the performance of four widely used tests of selection: SweepFinder, SweeD, OmegaPlus, and iHS. In order to consider the above questions, we utilize simulated data spanning a variety of selection coefficients and beneficial mutation rates. We demonstrate that the LD-based OmegaPlus performs best in terms of power to reject the neutral model under both equilibrium and non-equilibrium conditions-an important result regarding the relative effectiveness of linkage disequilibrium relative to site frequency spectrum based statics. The results presented here ought to serve as a useful guide for future empirical studies, and provides a guide for statistical choice depending on the history of the population under consideration. Moreover, the parameter space investigated and the Type-I and Type-II error rates calculated, represent a natural benchmark by which future statistics may be assessed.

Comparative sex chromosome genomics in snakes: differentiation, evolutionary strata, and lack of global dosage compensation.

Snakes exhibit genetic sex determination, with female heterogametic sex chromosomes (ZZ males, ZW females). Extensive cytogenetic work has suggested that the level of sex chromosome heteromorphism varies among species, with Boidae having entirely homomorphic sex chromosomes, Viperidae having completely heteromorphic sex chromosomes, and Colubridae showing partial differentiation. Here, we take a genomic approach to compare sex chromosome differentiation in these three snake families. We identify homomorphic sex chromosomes in boas (Boidae), but completely heteromorphic sex chromosomes in both garter snakes (Colubridae) and pygmy rattlesnake (Viperidae). Detection of W-linked gametologs enables us to establish the presence of evolutionary strata on garter and pygmy rattlesnake sex chromosomes where recombination was abolished at different time points. Sequence analysis shows that all strata are shared between pygmy rattlesnake and garter snake, i.e., recombination was abolished between the sex chromosomes before the two lineages diverged. The sex-biased transmission of the Z and its hemizygosity in females can impact patterns of molecular evolution, and we show that rates of evolution for Z-linked genes are increased relative to their pseudoautosomal homologs, both at synonymous and amino acid sites (even after controlling for mutational biases). This demonstrates that mutation rates are male-biased in snakes (male-driven evolution), but also supports faster-Z evolution due to differential selective effects on the Z. Finally, we perform a transcriptome analysis in boa and pygmy rattlesnake to establish baseline levels of sex-biased expression in homomorphic sex chromosomes, and show that heteromorphic ZW chromosomes in rattlesnakes lack chromosome-wide dosage compensation. Our study provides the first full scale overview of the evolution of snake sex chromosomes at the genomic level, thus greatly expanding our knowledge of reptilian and vertebrate sex chromosomes evolution.

Berberine and its derivatives: a patent review (2009 - 2012).

INTRODUCTION: Berberine, a protoberberine alkaloid, and its derivatives exhibit a wide spectrum of pharmacological activities. It has been used in traditional Chinese medicine and Ayurvedic medicine and current research evidences support its use for various therapeutic areas. AREAS COVERED: This review covers the patents on therapeutic activities of berberine and its derivatives in the years between 2009 and 2012. An extensive search was done to collect the patent information using European Patent Office database and SciFinder. The therapeutic areas covered include cancer, inflammation, infectious diseases, cardiovascular, metabolic disorders, and miscellaneous areas such as polycystic ovary syndrome, allergic diseases, and so on. EXPERT OPINION: Berberine along with its derivatives or in combination with other pharmaceutically active compounds or in the form of formulations has applications in various therapeutic areas such as cancer, inflammation, diabetes, depression, hypertension, and various infectious areas. Berberine has demonstrated wide physiological functions and has great potential to give a multipotent drug if some inherent problems on poor bioavailability and solubility are taken care of. Additionally, polyherbal formulations with berberine-containing plants as major ingredients can be successfully developed.