ALDH1A1 as a marker for metastasis initiating cells: A mechanistic insight.

Since metastasis accounts for the majority of cancer morbidity and mortality, attempts are focused to block metastasis and metastasis initiating cellular programs. It is generally believed that hypoxia, reactive oxygen species (ROS) and the dysregulated redox pathways regulate metastasis. Although induction of epithelial to mesenchymal transition (EMT) can initiate cell motility to different sites other than the primary site, the initiation of a secondary tumor at a distant site depends on self-renewal property of cancer stem cell (CSC) property. That subset of metastatic cells possessing CSC property are referred to as metastasis initiating cells (MICs). Among the different cellular intermediates regulating metastasis in response to hypoxia by inducing EMT and self-renewal property, ALDH1A1 is a critical molecule, which can be used as a marker for MICs in a wide variety of malignancies. The cytosolic ALDHs can irreversibly convert retinal to retinoic acid (RA), which initiates RA signaling, important for self-renewal and EMT. The metastasis permissive tumor microenvironment increases the expression of ALDH1A1, primarily through HIF1α, and leads to metabolic reprograming through OXPHOS regulation. The ALDH1A1 expression and its high activity can reprogram the cancer cells with the transcriptional upregulation of several genes, involved in EMT through RA signaling to manifest hybrid EMT or Hybrid E/M phenotype, which is important for acquiring the characteristics of MICs. Thus, the review on this topic highlights the use of ALDH1A1 as a marker for MICs, and reporters for the marker can be effectively used to trace the population in mouse models, and to screen drugs that target MICs.

NHERF1 in Microvilli of Vomeronasal Sensory Neurons.

In most mammals, the vomeronasal system detects a variety of (semio)chemicals that mediate olfactory-driven social and sexual behaviors. Vomeronasal chemosensation depends on G protein-coupled receptors (V1R, V2R, and FPR-rs) that operate at remarkably low stimulus concentrations, thus, indicating a highly sensitive and efficient signaling pathway. We identified the PDZ domain-containing protein, Na+/H+ exchanger regulatory factor-1 (NHERF1), as putative molecular organizer of signal transduction in vomeronasal neurons. NHERF1 is a protein that contains 2 PDZ domains and a carboxy-terminal ezrin-binding domain. It localizes to microvilli of vomeronasal sensory neurons and interacts with V1Rs. Furthermore, NHERF1 and Gαi2 are closely colocalized. These findings open up new aspects of the functional organization and regulation of vomeronasal signal transduction by PDZ scaffolding proteins.

Application of the Length of Index and Ring Fingers to Estimate the Stature.

INTRODUCTION: Stature contributes as a crucial element of an individual's physical appearance and can be instrumental in establishing their identity. In cases where the body is extensively mutilated, decomposed, or reduced to skeletal remains, stature becomes an essential component in identifying the unknown by means of measuring the skeletal remains. Its estimation relies on the principle that an individual's height has a definite and linear relationship with specific body parts and long bones. This process, together with assessing age, sex, and race constitutes the essential components of the anthropological protocol. Stature estimation can be accomplished through both anatomical and mathematical approaches. The present study clearly defines regression models for height estimation from finger lengths. The formula derived can prove particularly valuable in Medico-legal scenarios, as it can be applied effectively even when only a portion of the body is accessible. AIM: The purpose of the present study is to estimate the stature of individuals by measuring the length of the index and ring fingers. MATERIALS AND METHOD: The current study acquired three measurements, such as stature, right/left index finger length (RIFL/LIFL), and ring finger length (RFL), from 220 samples, including 110 males and 110 females, respectively, between the age groups of 20 and 60 years. RESULT: The application of the length of the index and ring finger in forensic investigations holds significance due to their potential as reliable predictors of an individual's height. According to the findings of the study, males showed significantly higher stature than females. A statistically significant correlation was also observed (p-value = 0) between stature and finger lengths (IFL, RFL) in both hands. The highest correlation coefficients were found for the left RFL (r = 0.688) in females and the LIFL (r = 0.552) in males. Additionally, males showed significantly longer index and RFL than females. Linear regression models for the estimation of stature from ring and index finger length were also derived successfully. CONCLUSION:  The results obtained from the present study exhibit potential use to evaluate the utility of measuring index and RFLs for determining stature and predicting the precision of regression models by employing those parameters. The models derived from this study can serve as corroborative evidence for identifying mutilated body parts or unknown remains.

Comparative study of male and female human hair: A microscopic analysis.

The outer cuticle, middle cortex, and inner medulla make up hair, which is an epidermal outgrowth. Hair is resilient under harsh natural conditions, thus it is frequently collected at crime scenes, making human hair analysis important in the forensic sciences field. It aids in the formation of a triangle connecting a crime scene, a victim, and a culprit. The aim of this study is to observe the microscopic structure of male and female human hair. Samples of hair specimens from males and females were collected. The materials used were ethanol to degrease and a stereomicroscope to observe the structural differences between the male and female hair samples. The comparison between male and female hair is done on the grounds of color, shaft profiles, the proximal and distal ends of the hair, cuticle, and surface texture, and the other found characters. This study of comparison between male and female hair specimens revealed that the hair color at the distal end is found to be brown for females while it is completely black in that of males, and the surface texture of males is found to have some irregularities while there are no irregularities in female. This study can be concluded that the structural comparison between male and female hair specimens can be used as evidence for forensic analysis at crime scenes.

Pattern-Corrected Mitotic Activity Index (PMAI): A Novel Prognosticator of Oral Squamous Cell Carcinoma.

OBJECTIVE: The main aim was to assess the efficiency of the Mitotic Activity Index (MAI) and a novel index devised by us, the Pattern-Corrected Mitotic Activity Index (PMAI) in prognostication of Oral Squamous Cell Carcinoma in terms of lymph node involvement, margin, recurrence and survival status. MATERIAL AND METHOD: The study group consisted of 60 cases of histologically-proven Oral Squamous Cell Carcinoma with known status of prognostic indicators. Hematoxylin and eosin stained sections of the tumor proper were utilized for assessment of mitotic activity and pattern of invasion. The Mitotic Activity Index and Pattern-Corrected Mitotic Activity Index were then calculated and correlated with the prognosticators. RESULTS: Mitotic Activity Index was higher in patients who had better survival and low recurrence rates. Pattern-Corrected Mitotic Activity Index showed the greatest percentage increase in relation to lymph node involvement as compared to the other indices. Kaplan Meier survival analysis showed that a higher Pattern-Corrected Mitotic Activity Index ( > 1.45) was associated with poorer survival (37.19 months). CONCLUSION: Lack of significant association of the Mitotic Activity Index in relation to prognosticators could be attributed to a tumor having a migratory phenotype rather than a proliferative phenotype as seen in late-stage tumors. Late-stage tumors have more of a poorer pattern of invasion which is reflected best by Pattern-Corrected Mitotic Activity Index by correlating with poorer survival and lymph node involvement.

Mucoadhesive microspheres of ferrous sulphate - A novel approach for oral iron delivery in treating anemia.

Ferrous sulphate is a widely used oral iron supplement with low bioavailability and substantial side effects. In this study ferrous sulphate has been coated with highly mucoadhesive polymers such as hydroxypropylmethyl cellulose (HP), chitosan (CS) and carbopol (CP) by spray drying technique to produce mucoadhesive polymer coated microspheres with good yield and high encapsulation efficiency. Mucoadhesive coating may allow these microspheres to get attached to the intestine and hence better absorption of ferrous sulphate may be achieved. in vitro release studies from the microspheres show that the release follows non-Fickian zero order drug release. CP and CSHP coated microspheres showed good swelling(∼1200 to 2400 %) and mucoadhesion properties (58-95 %) indicating that they can swell and get attached to the intestine for longer time period as compared to free ferrous sulphate. All the microspheres were found to be non-cytotoxic in Caco2 cell lines and fibroblast cell lines. Cell uptake studies conducted on Caco2 cell lines showed that uptake of microspheres containing ferrous sulphate has an increased and sustained release to the cell as compared to free ferrous sulphate. Though cell uptake studies showed an increase in uptake for ferrous sulphate microspheres, comparable efficacy was observed upon administering ferrous sulphate microspheres and ferrous sulphate to phenyl hydrazine induced anemic rats.

Selinexor (KPT-330) has antitumor activity against anaplastic thyroid carcinoma in vitro and in vivo and enhances sensitivity to doxorubicin.

Anaplastic thyroid carcinoma (ATC) is one of the most lethal malignancies having no effective treatment. Exportin-1 (XPO1) is the key mediator of nuclear export of many tumor suppressor proteins and is overexpressed in human cancers. In this study, we examined the therapeutic potential of selinexor (XPO1 inhibitor) against human ATC cells both in vitro and in vivo. Here, we showed that XPO1 is robustly expressed in primary ATC samples and human ATC cell lines. Silencing of XPO1 by either shRNA or selinexor significantly reduced cellular growth and induced cell cycle arrest, apoptosis of ATC cells by altering the protein expression of cancer-related genes. Moreover, selinexor significantly inhibited tumor growth of ATC xenografts. Microarray analysis showed enrichment of DNA replication, cell cycle, cell cycle checkpoint and TNF pathways in selinexor treated ATC cells. Importantly, selinexor decreased AXL and GAS6 levels in CAL62 and HTH83 cells and suppressed the phosphorylation of downstream targets of AXL signaling such as AKT and P70S6K. Finally, a combination of selinexor with doxorubicin demonstrated a synergistic decrease in the cellular proliferation of several ATC cells. These results provide a rationale for investigating the efficacy of combining selinexor and doxorubicin therapy to improve the outcome of ATC patients.