Understanding the cross-talk between human microbiota and gastrointestinal cancer for developing potential diagnostic and prognostic biomarkers.

The interaction between gut microbes and gastrointestinal (GI) tract carcinogenesis has always attracted researchers' attention to identify therapeutic targets or potential prognostic biomarkers. Various studies have suggested that the microbiota do show inflammation and immune dysregulation, which led to carcinogenesis in GI tract. In this review, we have focused on the role of microbes present in the gut, intestine, or faeces in GI tract cancers, including esophageal cancer, gastric cancer, and colorectal cancer. Herein, we have discussed the importance of the microbes and their metabolites, which could serve as diagnostic biomarkers for cancer detection, especially in the early stage, and prognostic markers. To maximize the effect of the treatment strategies, an accurate evaluation of the prognosis is imperative for clinicians. There is a vast difference in the microbiota profiles within a population and across the populations depending upon age, diet, lifestyle, genetic makeup, use of antibiotics, and environmental factors. Therefore, the diagnostic efficiency of the microbial markers needs to be further validated. A deeper understanding of the GI cancer and the host microbiota is needed to acquire pivotal information about disease status.

Immunotherapeutics in lung cancers: from mechanistic insight to clinical implications and synergistic perspectives.

BACKGROUND: Lung cancer is one of the highly lethal forms of cancer whose incidence has worldwide rapidly increased over the past few decades. About 80-85% of all lung cancer cases constitute non-small cell lung cancer (NSCLC), with adenocarcinoma, squamous cell carcinoma and large cell carcinoma as the main subtypes. Immune checkpoint inhibitors have led to significant advances in the treatment of a variety of solid tumors, significantly improving cancer patient survival rates. METHODS AND RESULTS: The cytotoxic drugs in combination with anti-PD-(L)1 antibodies is a new method that aims to reduce the activation of immunosuppressive and cancer cell prosurvival responses while also improving direct cancer cell death. The most commonly utilized immune checkpoint inhibitors for patients with non-small cell lung cancer are monoclonal antibodies (Atezolizumab, Cemiplimab, Ipilimumab, Pembrolizumab etc.) against PD-1, PD-L1, and CTLA-4. Among them, Atezolizumab (TECENTRIQ) and Cemiplimab (Libtayo) are engineered monoclonal anti programmed death ligand 1 (PD-L1) antibodies that inhibit binding of PD-L1 to PD-1 and B7.1. As a result, T-cell proliferation and cytokine synthesis are inhibited leading to restoring the immune homeostasis to fight cancer cells. CONCLUSIONS: In this review article, the path leading to the introduction of immunotherapeutic options in lung cancer treatment is described, with analyzing the benefits and shortages of the current immunotherapeutic drugs. In addition, possibilities to co-administer immunotherapeutic agents with standard cancer treatment modalities are also considered.

Application of curcumin nanoformulations to target folic acid receptor in cancer: Recent trends and advances.

Curcumin, derived from turmeric, has a strong anticancer potential known for millennia. The development of this phytochemical as a medicine has been hampered by several significant deficiencies, including its poor water solubility and low bioavailability. This review article discusses possibilities to overcome these bottlenecks by focusing on this natural polyphenol's nanoformulation. Moreover, preparation of curcumin conjugates containing folates as ligands for folic acid receptors can add a new important dimension in this field, allowing specific targeting of cancer cells, considering the significantly higher expression of these receptors in malignant tissues compared to normal cells. It is highly expected that simultaneous improvement of different aspects of curcumin in fighting against such a complex and multifaceted disease like cancer. Therefore, we can better comprehend cancer biology by developing a mechanistic understanding of curcumin, which will also inspire the scientific community to develop new pharmacological models, and exploration of emerging directions to revitalize application of natural products in cancer therapy.

Novel Biocompatible Green Silver Nanoparticles Efficiently Eliminates Multidrug Resistant Nosocomial Pathogens and Mycobacterium Species.

Bacterial infection is a major crisis of 21st era and the emergence of multidrug resistant (MDR) pathogens cause significant health problems. We developed, green chemistry-based silver nanoparticles (G-Ag NPs) using Citrus pseudolimon fruit peel extract. G-Ag NPs has a spherical shape in the range of ~ 40 nm with a surface charge of - 31 Mv. This nano-bioagent is an eco-friendly tool to combat menace of MDR. Biochemical tests prove that G-Ag NPs are compatible with human red blood cells and peripheral blood mononuclear cells. There have been many reports on the synthesis of silver nanoparticles, but this study suggests a green technique for making non-cytotoxic, non-hemolytic organometallic silver nanoparticles with a high therapeutic index for possible use in the medical field. On the same line, G-Ag NPs are very effective against Mycobacterium sp. and MDR strains including Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, and Acinetobacter baumannii isolated from patient samples. Based on it, we filed a patent to Indian Patent Office (reference no. 202111048797) which can revolutionize the prevention of biomedical device borne infections in hospital pre/post-operated cases. This work could be further explored in future by in vivo experimentation with mice model to direct its possible clinical utility. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01061-0.

TOPLESS in the regulation of plant immunity.

KEY MESSAGE: This review presents the multiple ways how topless and topless-related proteins regulate defense activation in plants and help in optimizing the defense-growth tradeoff. Eukaryotic gene expression is tightly regulated at various levels by hormones, transcription regulators, post-translational modifications, and transcriptional coregulators. TOPLESS (TPL)/TOPLESS-related (TPR) corepressors regulate gene expression by interacting with other transcription factors. TPRs regulate auxin, gibberellins, jasmonic acid, strigolactone, and brassinosteroid signaling in plants. In general, except for GA, TPLs suppress these signaling pathways to prevent unwanted activation of hormone signaling. The association of TPL/TPRs in these hormonal signaling reflects a wide role of this class of corepressors in plants' normal and stress physiology. The involvement of TPL in immune responses was first demonstrated a decade ago as a repressor of DND1 and DND2 that are negative regulators of plant immune response. Over the last decade, several research groups have established a larger role of TPL/TPRs in plant immunity during both pattern- and effector-triggered immunity. Very recent research unraveled the significant involvement of TPRs in balancing the growth and defense trade-off. TPRs, along with proteasomal degradation complex, miRNA, and phasiRNA, suppress the activation of autoimmunity in plants under normal conditions and promote defense under pathogen attack.

A comparative molecular dynamic simulation study on potent ligands targeting mTOR/FRB domain for breast cancer therapy.

Our study aimed to develop and find out the best drug candidate against the mechanistic target of rapamycin (mTOR/FRB) domain having a critical role in the aetiology of breast cancer. The FKBP12-rapamycin-binding (FRB) domain in the essential phosphoinositide 3 kinase/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway has been a vital player in the disease progression in breast cancer. By using structure-based drug designing , the best possible targets have been identified and developed. The three-dimensional structure of the target protein was generated using I-TASSER. The ligands were generated against the most suitable target active site using standard tools for active site identification. Furthermore, the seed molecule was drawn using Chemsketch, which was then grown into the pocket using Ligbuilder. The obtained ligands were further validated using online programs for bioavailability and toxicity, followed by molecular dynamic simulations. The study concludes that the equilibrated NVT-NPT complexes indicate LIG2 stability over LIG3. RMSD and RMSF have shown that the complex of LIG2 is more stable than LIG3. LIG2 has the potential antagonistic properties to target the mTOR/FRB domain and has therapeutic implications for breast cancer.

Rhamnolipid the Glycolipid Biosurfactant: Emerging trends and promising strategies in the field of biotechnology and biomedicine.

Rhamnolipids (RLs) are surface-active compounds and belong to the class of glycolipid biosurfactants, mainly produced from Pseudomonas aeruginosa. Due to their non-toxicity, high biodegradability, low surface tension and minimum inhibitory concentration values, they have gained attention in various sectors like food, healthcare, pharmaceutical and petrochemicals. The ecofriendly biological properties of rhamnolipids make them potent materials to be used in therapeutic applications. RLs are also known to induce apoptosis and thus, able to inhibit proliferation of cancer cells. RLs can also act as immunomodulators to regulate the humoral and cellular immune systems. Regarding their antimicrobial property, they lower the surface hydrophobicity, destruct the cytoplasmic membrane and lower the critical micelle concentration to kill the bacterial cells either alone or in combination with nisin possibly due to their role in modulating outer membrane protein. RLs are also involved in the synthesis of nanoparticles for in vivo drug delivery. In relation to economic benefits, the post-harvest decay of food can be decreased by RLs because they prevent the mycelium growth, spore germination of fungi and inhibit the emergence of biofilm formation on food. The present review focuses on the potential uses of RLs in cosmetic, pharmaceutical, food and health-care industries as the potent therapeutic agents.

Sustainable and green trends in using plant extracts for the synthesis of biogenic metal nanoparticles toward environmental and pharmaceutical advances: A review.

Conventionally utilized physical and chemical routes for constructing nanoparticles are not eco-friendly. They are associated with many shortcomings like the requirement of specially designed equipment, templates, extremely high temperature, and pressure. Biosynthesis seems to be drawn unequivocal attention owing to its upsurge of applications in different fields like; energy, nutrition, pharmaceutical, and medicinal sciences. To harness the biological sources, the present review describes an environment-friendly route to generate biogenic nanoparticles from the natural plant extracts and the followed mechanisms for their synthesis, growth, and stabilization. The present review summarizes the recent trends involved in the photosynthesis of metallic nanoparticles and their effective use in controlling malaria, hepatitis, cancer, like various endemic diseases. Also, various characterization approaches, such as UV-visible spectrophotometry, Fourier transform infrared spectroscopy, powder X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and energy-dispersive X-ray spectroscopy, are discussed here examine the properties of as-fabricated nanoparticles. Various plant parts like leaves, stems, barks, fruit, and flowers are rich in flavonoids, phenols, steroids, terpenoids, enzymes, and alkaloids, thereby playing an essential role in reducing metal ions that generate metallic nanoparticles. Herein, the uniqueness of phytofabricated nanoparticles along with their distinctive antibacterial, antioxidant, cytotoxic, and drug delivery properties are featured. Lastly, this work highlights the various challenges and future perspectives to further synthesize biogenic metal nanoparticles toward environmental and pharmaceutical advances in the coming years.

Apoptosis induction in lung and prostate cancer cells through silver nanoparticles synthesized from Pinus roxburghii bioactive fraction.

The current study was carried out to synthesize silver nanoparticles (AgNPs) via bioactive fraction of Pinus roxburghii needles using a simple, cost-effective, and eco-friendly green chemistry method. As butanol fraction of P. roxburghii exhibited maximum anticancer activity on lung adenocarcinomas (A549) as compared to other fractions therefore, butanol fraction was used to synthesize silver nanoparticles (PNb-AgNPs). The characterization studies by UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) and selected area electron diffraction (SAED) confirmed the synthesis of the nanoparticles. The field emission scanning electron microscopy (FESEM) and high-resolution transmission electron microscopy (HRTEM) analysis showed the spherical structure of nanoparticles with an average diameter of approximately 80 nm. Interestingly, PNb-AgNPs exhibited significant cytotoxicity towards both A549 and prostatic small cell carcinomas (PC-3) with IC50 values of 11.28 ± 1.28 µg/ml and 56.27 ± 1.17 µg/ml, respectively, while lacking toxicity against normal human breast epithelial cells (fR2) and human peripheral blood lymphocytes (PBL). Further, enhanced reactive oxygen species generation, mitochondrial depolarization, apoptotic cell population (sub-G1) and DNA fragmentation observed in cancer cells were treated with PNb-AgNPs. Apoptosis was demonstrated by caspase-3 and PARP-1 activation in PNb-AgNPs-pretreated cancer cells. These results strongly suggest that PNb-AgNPs are capable of inducing cancer cell death and could act as a therapeutic nanoformulation for cancer.

Immunomodulation-mediated anticancer activity of a novel compound from Brugmansia suaveolens leaves.

Immunomodulation activity-guided fractionation of ethanol extract of Brugmansia suaveolens leaves was carried out to isolate a novel compound SUPH036-022A (1) by co-culturing the test fraction/compound activated PBMC with MCF7 and A549 cancer cell lines. Assessment of immune markers in PBMC, and analysis of apoptosis markers and cell cycle was carried out for cancer cells. The structure of the isolated compound was elucidated by spectral analysis. Compound 1 enhanced the secretion of immune markers, IL-2 and IFN-γ, from PBMC. Further, compound 1 treated PBMC increased cell death in MCF7 and A549 cell lines and induced ROS production and mitochondrial membrane perturbation, leading to apoptosis. Flow cytometry analysis revealed; compound 1 stimulated PBMC to cause a five-fold increase in cell cycle perturbations in the sub-G1 stage of cancer cells as compared to the negative control. The compound, in the absence of PBMC, only had a weak cytotoxic activity against these cell lines. Thus, compound 1 is a novel lead for immunomodulation-mediated anticancer activity.

Circadian oscillator proteins across the kingdoms of life: structural aspects.

Circadian oscillators are networks of biochemical feedback loops that generate 24-hour rhythms in organisms from bacteria to animals. These periodic rhythms result from a complex interplay among clock components that are specific to the organism, but share molecular mechanisms across kingdoms. A full understanding of these processes requires detailed knowledge, not only of the biochemical properties of clock proteins and their interactions, but also of the three-dimensional structure of clockwork components. Posttranslational modifications and protein-protein interactions have become a recent focus, in particular the complex interactions mediated by the phosphorylation of clock proteins and the formation of multimeric protein complexes that regulate clock genes at transcriptional and translational levels. This review covers the structural aspects of circadian oscillators, and serves as a primer for this exciting realm of structural biology.

Hand preference and intolerance of uncertainty: Atypical cerebral lateralization advantages lower intolerance of uncertainty.

Left and inconsistent hand preferences are the markers of atypical brain organization that relate with cognitive and behavioural traits as well as with developmental disorders, whereas intolerance of uncertainty is the trait of inability to bear future uncertainty that mediates anxiety disorders and depression. In the present study, relationship of hand preference with intolerance of uncertainty was studied in a sample of 862 college students (age: M = 21.4 years, SD = 3.12). Results show that left-handers had lower prospective intolerance of uncertainty than right-handers. Furthermore, inconsistent right-handers had lower inhibitive intolerance of uncertainty than consistent right-handers. Thus, the present study supports the likelihood that atypical brain organization advantages tolerance of uncertainty (i.e., lower intolerance of uncertainty). Implications of these findings for understanding the contribution of intolerance of uncertainty to anxiety have been discussed.

New Insights into Molecular Links Between Microbiota and Gastrointestinal Cancers: A Literature Review.

Despite decades of exhaustive research on cancer, questions about cancer initiation, development, recurrence, and metastasis have still not been completely answered. One of the reasons is the plethora of factors acting simultaneously in a tumour microenvironment, of which not all have garnered attention. One such factor that has long remained understudied and has only recently received due attention is the host microbiota. Our sheer-sized microbiota exists in a state of symbiosis with the body and exerts significant impact on our body's physiology, ranging from immune-system development and regulation to neurological and cognitive development. The presence of our microbiota is integral to our development, but a change in its composition (microbiota dysbiosis) can often lead to adverse effects, increasing the propensity of serious diseases like cancers. In the present review, we discuss environmental and genetic factors that cause changes in microbiota composition, disposing of the host towards cancer, and the molecular mechanisms (such as ß-catenin signalling) and biochemical pathways (like the generation of oncogenic metabolites like N-nitrosamines and hydrogen sulphide) that the microbiota uses to initiate or accelerate cancers, with emphasis on gastrointestinal cancers. Moreover, we discuss how microbiota can adversely influence the success of colorectal-cancer chemotherapy, and its role in tumour metastasis. We also attempted to resolve conflicting results obtained for the butyrate effect on tumour suppression in the colon, often referred to as the 'butyrate paradox'. In addition, we suggest the development of microbiota-based biomarkers for early cancer diagnosis, and a few target molecules of which the inhibition can increase the overall chances of cancer cure.

EARLY FLOWERING4 recruitment of EARLY FLOWERING3 in the nucleus sustains the Arabidopsis circadian clock.

The plant circadian clock is proposed to be a network of several interconnected feedback loops, and loss of any component leads to changes in oscillator speed. We previously reported that Arabidopsis thaliana EARLY FLOWERING4 (ELF4) is required to sustain this oscillator and that the elf4 mutant is arrhythmic. This phenotype is shared with both elf3 and lux. Here, we show that overexpression of either ELF3 or LUX ARRHYTHMO (LUX) complements the elf4 mutant phenotype. Furthermore, ELF4 causes ELF3 to form foci in the nucleus. We used expression data to direct a mathematical position of ELF3 in the clock network. This revealed direct effects on the morning clock gene PRR9, and we determined association of ELF3 to a conserved region of the PRR9 promoter. A cis-element in this region was suggestive of ELF3 recruitment by the transcription factor LUX, consistent with both ELF3 and LUX acting genetically downstream of ELF4. Taken together, using integrated approaches, we identified ELF4/ELF3 together with LUX to be pivotal for sustenance of plant circadian rhythms.

15 kDa granulysin causes differentiation of monocytes to dendritic cells but lacks cytotoxic activity.

Granulysin is expressed as two isoforms by human cytotoxic cells: a single mRNA gives rise to 15 kDa granulysin, a portion of which is cleaved to a 9 kDa protein. Studies with recombinant 9 kDa granulysin have demonstrated its cytolytic and proinflammatory properties, but much less is known about the biologic function of the 15 kDa isoform. In this study, we show that the subcellular localization and functions of 9 and 15 kDa granulysin are largely distinct. Nine kilodalton granulysin is confined to cytolytic granules that are directionally released following target cell recognition. In contrast, 15 kDa granulysin is located in distinct granules that lack perforin and granzyme B and that are released by activated cytolytic cells. Although recombinant 9 kDa granulysin is cytolytic against a variety of tumors and microbes, recombinant 15 kDa granulysin is not. The 15 kDa isoform is a potent inducer of monocytic differentiation to dendritic cells, but the 9 kDa isoform is not. In vivo, mice expressing granulysin show markedly improved antitumor responses, with increased numbers of activated dendritic cells and cytokine-producing T cells. Thus, the distinct functions of granulysin isoforms have major implications for diagnosis and potential new therapies for human disease.

Covalent-Organic Framework-Based Materials in Theranostic Applications: Insights into Their Advantages and Challenges.

Nanomedicine has been essential in bioimaging and cancer therapy in recent years. Nanoscale covalent-organic frameworks (COFs) have been growing as an adequate classification of biomedical nanomaterials with practical application prospects because of their increased porosity, functionality, and biocompatibility. The high sponginess of COFs enables the incorporation of distinct imaging and therapeutic mechanisms with a better loading efficiency. Nevertheless, preliminary biocompatibility limits their possibility for clinical translation. Thus, cutting-edge nanomaterials with high biocompatibility and improved therapeutic efficiency are highly expected to fast-track the clinical translation of nanomedicines. The inherent effects of nanoscale COFs, such as proper size, modular pore geometry and porosity, and specific postsynthetic transformation through simple organic changes, make them particularly appealing for prospective nanomedicines. The organic building blocks of COFs may also be postmodified for particular binding to biomarkers. The exceptional features of COFs cause them to be an encouraging nanocarrier for bioimaging and therapeutic applications. In this review, we have systematically discussed the advances of COFs in the field of theranostics by providing essential features of COFs along with their synthetic methods. Further, the applications of COFs in the field of theranostics (such as drug delivery systems, photothermal, and photodynamic therapy) are discussed in detail with the help of available literature to date. Furthermore, the advantages of COFs over other materials for therapeutics and drug delivery are discussed. Finally, the review concludes with potential future COF applications in the theranostic field.

Polymer-mediated nanoformulations: a promising strategy for cancer immunotherapy.

Engineering polymer-based nano-systems have attracted many researchers owing to their unique qualities like shape, size, porosity, mechanical strength, biocompatibility, and biodegradability. Both natural and synthetic polymers can be tuned to get desired surface chemistry and functionalization to improve the efficacy of cancer therapy by promoting targeted delivery to the tumor site. Recent advancements in cancer immunoediting have been able to manage both primary tumor and metastatic lesions via activation of the immune system. The combinations of nano-biotechnology and immunotherapeutic agents have provided positive outcomes by enhancing the host immune response in cancer therapy. The nanoparticles have been functionalized using antibodies, targeted antigens, small molecule ligands, and other novel agents that can interact with biological systems at nanoscale levels. Several polymers, such as polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), poly(ε-caprolactone) (PCL), and chitosan, have been approved by the Food and Drug Administration for clinical use in biomedicine. The polymeric nanoformulations such as polymers-antibody/antigen conjugates and polymeric drug conjugates are currently being explored as nanomedicines that can target cancer cells directly or target immune cells to promote anti-cancer immunotherapy. In this review, we focus on scientific developments and advancements on engineered polymeric nano-systems in conjugation with immunotherapeutic agents targeting the tumor microenvironment to improve their efficacy and the safety for better clinical outcomes.

Alpha-synuclein interaction with mitochondria is the final mechanism of ferroptotic death induced by erastin in SH-SY5Y cells.

Ferroptosis has been characterized as a form of iron-dependent regulated cell death accompanied by an accumulation of reactive oxygen species and lipid oxidation products along with typical morphological alterations in mitochondria. Ferroptosis is activated by diverse triggers and inhibited by ferrostatin-1 and liproxstatin-1, apart from iron chelators and several antioxidants, and the process is implicated in multiple pathological conditions. There are, however, certain ambiguities about ferroptosis, especially regarding the final executioner of cell death subsequent to the accumulation of ROS. This study uses a typical inducer of ferroptosis such as erastin on SH-SY5Y cells, and shows clearly that ferroptotic death of cells is accompanied by the loss of mitochondrial membrane potential and intracellular ATP content along with an accumulation of oxidative stress markers. All these are prevented by ferrostatin-1 and liproxstatin-1. Additionally, cyclosporine A prevents mitochondrial alterations and cell death induced by erastin implying the crucial role of mitochondrial permeability transition pore (mPTP) activation in ferroptotic death. Furthermore, an accumulation of α-synuclein occurs during erastin induced ferroptosis which can be inhibited by ferrostatin-1 and liproxstatin-1. When the knock-down of α-synuclein expression is performed by specific siRNA treatment of SH-SY5Y cells, the mitochondrial impairment and ferroptotic death of the cells induced by erastin are markedly prevented. Thus, α-synuclein through the involvement of mPTP appears to be the key executioner protein of ferroptosis induced by erastin, but it needs to be verified if it is a generalized mechanism of ferroptosis by using other inducers and cell lines.

Granulysin delivered by cytotoxic cells damages endoplasmic reticulum and activates caspase-7 in target cells.

Granulysin is a human cytolytic molecule present in cytotoxic granules with perforin and granzymes. Recombinant 9-kDa granulysin kills a variety of microbes, including bacteria, yeast, fungi, and parasites, and induces apoptosis in tumor cells by causing intracellular calcium overload, mitochondrial damage, and activation of downstream caspases. Reasoning that granulysin delivered by cytotoxic cells may work in concert with other molecules, we crossed granulysin transgenic (GNLY(+/-)) mice onto perforin (perf)- or granzyme B (gzmb)-deficient mice to examine granulysin-mediated killing in a more physiologic whole-cell system. Splenocytes from these animals were activated in vitro with IL-15 to generate cytolytic T cells and NK cells. Cytotoxic cells expressing granulysin require perforin, but not granzyme B, to cause apoptosis of targets. Whereas granzyme B induces mitochondrial damage and activates caspases-3 and -9 in targets, cytotoxic cell-delivered granulysin induces endoplasmic reticulum stress and activates caspase-7 with no effect on mitochondria or caspases-3 and -9. In addition, recombinant granulysin and cell-delivered granulysin activate distinct apoptotic pathways in target cells. These findings suggest that cytotoxic cells have evolved multiple nonredundant cell death pathways, enabling host defense to counteract escape mechanisms employed by pathogens or tumor cells.

Factor structure and measurement invariance of Schizotypal Personality Questionnaire-Brief Revised (Updated) in India.

AIM: Schizotypal Personality Questionnaire-Brief Revised-Updated (SPQ-BRU) is an easy-to-conduct, theoretically consistent, and psychometrically better measure of schizotypal personality. However, its study is limited to developed countries. Thus, in the present study, we tested the factor structure and measurement invariance of SPQ-BRU in India. METHODS: A sample of 734 college students was selected from two sites (n = 614 from Muzaffarnagar in western Uttar Pradesh and n = 120 from Guhana in Haryana). Confirmatory factor analysis was used to test the good fitness of the different models of SPQ-BRU and the measurement invariance across sex and region. RESULTS: The first-order nine-factor model was a better-fit model (among a set of first-order and second-order models), whereas the second-order three-factor model was a more parsimonious good-fit model of SPQ-BRU. The nine-factor model was strongly invariant across sex and region. Women had higher social anxiety, ideas of reference, and lower constricted affect than men. Moreover, the Gohana sample was higher on several schizotypal personality facades than the Muzaffarnagar sample. CONCLUSIONS: The present study supported the cross-cultural validity of schizotypal personality and partially established a reliable and valid SPQ-BRU-Hindi language version.