Oral microbiota in cancer: could the bad guy turn good with application of polyphenols?

The human oral cavity is comprised of dynamic and polynomial microbes which uniquely reside in the microenvironments of oral cavities. The cumulative functions of the symbiotic microbial communities maintain normal homeostasis; however, a shifted microbiota yields a dysbiosis state, which produces local and systemic diseases including dental caries, periodontitis, cancer, obesity and diabetes. Recent research reports claim that an association occurs between oral dysbiosis and the progression of different types of cancers including oral, gastric and pancreatic ones. Different mechanisms are proposed for the development of cancer, such as induction of inflammatory reactions, production of carcinogenic materials and alteration of the immune system. Medications are available to treat these associated diseases; however, the current strategies may further worsen the disease by unwanted side effects. Natural-derived polyphenol molecules significantly inhibit a wide range of systemic diseases with fewer side effects. In this review, we have displayed the functions of the oral microbes and we have extended the report regarding the role of polyphenols in oral microbiota to maintain healthy conditions and prevention of diseases with emphasis on the treatment of oral microbiota-associated cancer.

Epidemiologic profile and outcome of primary pediatric brain tumors in Iran: retrospective study and literature review.

PURPOSE: Primary pediatric tumors are the most common solid tumors in children. There are limited reports on the management and outcome of these tumors in the developing countries. In recent years, advances have been done in the diagnosis, treatment, and outcome of these tumors. The aim of this study was to evaluate the histopathology, characteristics, and outcome of primary pediatric tumors in Iran. METHODS: This retrospective study examines primary brain tumors in children below 14 years of age who have undergone surgery. Histopathological characteristics according to WHO 2017 classification, age, sex, tumor resection rate, and patient outcome were extracted and studied. The results of the study were compared with the results of similar reports from neighboring countries and other parts of the world. RESULTS: In this study, 199 primary pediatric tumors were examined. Out of 199 cases, 114 cases were males, and 85 cases were females, and the male/female ratio was 1.34. The most common tumor group in this study was astrocytic tumors (68.3%) and the most common tumor was pilocytic astrocytoma (22.1%). In terms of malignancy, 50.7% of tumors were benign, and 49.3% were malignant. Total resection was done in 46% and subtotal resection in 35%. The mortality rate was found 19.2%. َAmong the remaining cases during follow-up, 76.6% had a good outcome without neurological deficits or mild disability and 23.4% had moderate to severe disability. CONCLUSIONS: The results of the study in terms of pathology and demographic characteristics were mainly similar to other reports. The mean age of patients was lower, and the patients' outcome was better than the other countries in the region.

Local vancomycin therapy to reduce surgical site infection in adult spine surgery: a randomized prospective study.

PURPOSE: This prospective randomized controlled trial hypothesizes that intra wound vancomycin reduces postoperative infection. METHODS: In this RCT study, the patients were randomly divided into two groups of treatment and control. In the treatment group, 1-2 g of intra wound vancomycin was used, and no drug was used for the control group. SSI and the type of microorganism causing postoperative infection were assessed at a three-month follow-up. Factors affecting postoperative infection such as age, sex, site of operation, surgical levels, and risk factors affecting postoperative infection, such as diabetes, blood pressure, ischemic heart disease, smoking, blood transfusion, BMI, neurologic deficit, CSF leakage, UTI, COPD and surgery time were examined in two groups. RESULTS: In this study, 375 patients, including 187patients in the treatment group and 188 patients in the control group, were studied. Among the patients, 228 had surgery without instrumentation, and 147 had surgery with instrumentation. There were 12 cases of SSI in the treatment group and 11 in the control group, and there was no statistically significant difference between the two groups. There was no difference between the two groups with and without instrumentation in the evaluation of postoperative infection. In the subgroups with and without instruments, there was no significant difference between treatment and control groups. Due to the microorganism causing the infection, gram-negative bacteria were more common in the treatment group. CONCLUSION: Intra-wound vancomycin has no effect on SSI; in addition, it can increase the rate of gram-negative infections.

Arglabin could target inflammasome-induced ARDS and cytokine storm associated with COVID-19.

Arglabin (l(R),10(S)-epoxy-5(S),5(S),7(S)-guaia-3(4),ll(13)-dien-6,12-olide), is a natural sesquiterpene γ-lactone which was first isolated from Artemisia glabella. The compound has been shown to possess anti-inflammatory activity through inhibition of the NLR Family pyrin domain-containing 3 (NLRP3) inflammasome and production of proinflammatory cytokines including interleukin (IL)-1ß and IL-18. A more hydrophilic derivative of the compound also exhibited antitumor activity in the breast, colon, ovarian, and lung cancer. Some other synthetic derivatives of the compound have also been synthesized with antitumor, cytotoxic, antibacterial, and antifungal activities. Since both NLRP3 inflammasome and cytokine storm are associated with the pathogenesis of COVID-19 and its lethality, compounds like arglabin might have therapeutic potential to attenuate the inflammasome-induced acute respiratory distress syndrome and/or the cytokine storm associated with COVID-19.

DihydrofolateReductase (DHFR) Inhibitors: A Comprehensive Review.

BACKGROUND: Dihydrofolate reductase (DHFR) is an indispensable enzyme required for the survival of most prokaryotic and eukaryotic cells as it is involved in the biosynthesis of essential cellular components. DHFR has attracted a lot of attention as a molecular target for various diseases like cancer, bacterial infection, malaria, tuberculosis, dental caries, trypanosomiasis, leishmaniasis, fungal infection, influenza, Buruli ulcer, and respiratory illness. Various teams of researchers have reported different DHFR inhibitors to explore their therapeutic efficacy. Despite all the progress made, there is a strong need to find more novel leading structures, which may be used as better and safe DHFR inhibitors, especially against the microorganisms which are resistant to the developed drug candidates. OBJECTIVE: This review aims to pay attention to recent development, particularly made in the past two decades and published in this field, and pay particular attention to promising DHFR inhibitors. Hence, an attempt has been made in this article to highlight the structure of dihydrofolate reductase, the mechanism of action of DHFR inhibitors, most recently reported DHFR inhibitors, diverse pharmacological applications of DHFR inhibitors, reported in-silico study data and recent patents based on DHFR inhibitors to comprehensively portray the current scenery for researchers interested in designing novel DHFR inhibitors. CONCLUSION: A critical review of recent studies revealed that most novel DHFR inhibitor compounds either synthetically or naturally derived are characterized by the presence of heterocyclic moieties in their structure. Non-classical antifolates like trimethoprim, pyrimethamine, and proguanil are considered excellent templates to design novel DHFR inhibitors, and most of them have substituted 2,4-diamino pyrimidine motifs. Targeting DHFR has massive potential to be investigated for newer therapeutic possibilities to treat various diseases of clinical importance.

Predictive Value of Blood Markers in Nonfunctional Pituitary Adenomas using Artificial Neural Network.

Background: Nonfunctioning pituitary adenomas (NFPAs) are the most common pituitary tumors and although they do not secrete hormones, they can have systemic effects. These tumors affect the function of other organs in the body by exerting pressure on the pituitary gland. There are differences between biomarkers NFPAs compared to healthy people. This study was conducted to show blood marker changes in adenomas compared to healthy people. Materials and Methods: This article compared the blood markers of NFPAs with healthy individuals retrospectively. The difference between blood markers in the two groups was statistically investigated where the predictive value of blood markers in the differentiation of the two groups was determined. An artificial neural network was also designed using the blood markers with its accuracy and predictive value determined. Results: A total of 96 NFPAs (nonfunctional pituitary adenoma) and 96 healthy individuals were evaluated. There was statistically a significant difference and positive correlation in platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, and derived neutrophil to lymphocyte ratio between NFPAs and healthy individuals. There was a significant and negative correlation between red blood cell (RBC), lymphocyte, and monocyte between the two groups. RBC as an independent factor was associated with NFPAs. In this study, the artificial neural network was able to differentiate between NFPTs cases and healthy individuals with an accuracy of 81.2%. Conclusion: There are differences between blood markers in NFPAs relative to healthy people and the artificial neural network can accurately differentiate between them.

Short interfering RNA in colorectal cancer: is it wise to shoot the messenger?

Colorectal cancer (CRC) is the third most common cancer and the leading cause of gastrointestinal cancer death. 90% of people diagnosed with colorectal cancer are over the age of 50; nevertheless, the illness is more aggressive among those detected at a younger age. Chemotherapy-based treatment has several adverse effects on both normal and malignant cells. The primary signaling pathways implicated in the advancement of CRC include hedgehog (Hh), janus kinase and signal transducer and activator of transcription (JAK/STAT), Wingless-related integration site (Wnt)/ß-catenin, transforming growth factor-ß (TNF-ß), epidermal growth factor receptor (EGFR)/Mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), nuclear factor kappa B (NF-κB), and Notch. Loss of heterozygosity in tumor suppressor genes like adenomatous polyposis coli, as well as mutation or deletion of genes like p53 and Kirsten rat sarcoma viral oncogene (KRAS), are all responsible for the occurrence of CRC. Novel therapeutic targets linked to these signal-transduction cascades have been identified as a consequence of advances in small interfering RNA (siRNA) treatments. This study focuses on many innovative siRNA therapies and methodologies for delivering siRNA therapeutics to the malignant site safely and effectively for the treatment of CRC. Treatment of CRC using siRNA-associated nanoparticles (NPs) may inhibit the activity of oncogenes and MDR-related genes by targeting a range of signaling mechanisms. This study summarizes several siRNAs targeting signaling molecules, as well as the therapeutic approaches that might be employed to treat CRC in the future.

A Concise Review of Common Plant-derived Compounds as a Potential Therapy for Alzheimer's Disease and Parkinson's Disease: Insight into Structure-Activity-Relationship.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurological illnesses that affect people in their later years. Memory loss is the hallmark of Alzheimer's disease, while dyskinesia, or loss of mobility, is associated with muscle rigidity and tremors in PD. Both diseases are unrelated, however, they do have a few similarities associated with extrapyramidal abnormalities, particularly stiffness, which has been linked to concomitant PD in many AD patients. Increased levels of IL-1, IL-6, and TNF in the AD and PD patients can be regarded as evidence of systemic inflammation associated with each of these neurodegenerative disorders. One of the primary variables in the progression of neurodegenerative disorders is oxidative stress. Many medicinal plants and their secondary metabolites have been claimed to be able to help people with neurodegenerative disorders like AD and PD. Anti-inflammatory, antioxidant, antiapoptotic, monoamine oxidase inhibition, acetylcholinesterase, and neurotrophic pursuits are among the major mechanisms identified by which phytochemicals exert their neuroprotective effects and potential maintenance of neurological health in old age. In regard to neurodegenerative disorders, numerable plant-based drugs like alkaloids, iridoids, terpenes, and flavones are employed for the treatment. Structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) are used to investigate the link between bioactivity and the chemical configuration of substances. The SAR and QSAR of natural plant components employed in AD and PD are discussed in the current review.

A new method for the simultaneous analysis of strychnine and brucine in Strychnos nux-vomica unprocessed and processed seeds using a carbon-paste electrode modified with multi-walled carbon nanotubes.

INTRODUCTION: Strychnos nux-vomica L. (Loganiaceae), widely used in folk medicine, is grown extensively in southern Asian countries. Its major bioactive constituents are strychnine and brucine, which are frequently used in traditional herbal medicines for treatment of nervous diseases, vomiting and traumatic pain. OBJECTIVE: A new method using a carbon-paste electrode modified with multi-walled carbon nanotubes (CNT/CPE) was developed and validated for single or simultaneous determination of strychnine and brucine in Strychnos nux-vomica seeds. Additionally, an environmentally friendly method was successfully applied to reduce the levels of strychnine and brucine in seeds. MATERIALS AND METHODS: Cyclic voltammetry, chronocoulometry and differential pulse voltammetry were used with multi-walled carbon nanotube modified carbon-paste electrodes. RESULTS: The peak currents increase linearly with the strychnine and brucine concentrations in the ranges of 50-1000 and 5-355 µ m, and the detection limits for strychnine and brucine were 0.43 and 0.28 µ m, respectively. Of the processing methods used, the greatest reduction in the strychnine and brucine levels was observed in samples processed using milk and saltwater. CONCLUSION: A new, sensitive and selective method was developed for the measurement of strychnine and brucine. This method was successfully applied to the determination of strychnine and brucine in unprocessed and processed Strychnos nux-vomica seed.

Effect of Ustukhuddus Alavi, a multi-herbal product, on the cognitive performance of adolescent female students.

ETHNOPHARMACOLOGICAL RELEVANCE: Ustukhuddus Alavi is a polyherbal formula which is introduced by Persian medicine scholars. It is traditionally used to treat brain disorders and is claimed to do so by preprocessing and cleansing the waste products from the brain. According to Persian medicine, the disposal of brain waste products is necessary for optimal cognitive performance. AIM OF THE STUDY: Sustaining optimal cognitive performance is crucial for ideal quality of life and higher academic achievements in high school students. The objective of this study was to determine the effects of this multi-component herbal product on the cognitive performance and salivary cortisol levels of adolescent female students. MATERIALS AND METHODS: The effect of a 6-week randomly assigned Ustukhuddus Alavi versus placebo administration on cognitive performance was assessed by the paced auditory serial addition test (PASAT) at the baseline and after the 3- and 6-week intake of Ustukhuddus Alavi or placebo and the one-month follow-up in 86 healthy female high school students in grades 10 and 11. Additionally, we measured the levels of salivary cortisol of the students pre- and post-intervention. RESULTS: Significant mean difference between the Ustukhuddus Alavi and placebo groups in three of the paced auditory serial addition test (PASAT) subscales, namely mental health (p-value = 0.006), sustained attention (p-value = 0.001) and mental fatigue (p-value = 0.001), were observed after six weeks. We also found a significant difference between the mean salivary cortisol level of the two groups after the intervention (p-value = 0.047). CONCLUSIONS: These findings reveal that the intake of the multi-ingredient herbal product Ustukhuddus Alavi for six weeks can be helpful for cognitive function and cortisol levels in female high school students. These positive effects seem to be related to the increase in sustained attention and the decrease in mental fatigue.

Insight into the corrosion inhibition of Biebersteinia multifida root extract for carbon steel in acidic medium.

In this project, the protective effect of Biebersteinia multifida root extract (BMRE) against corrosion of 1018 low carbon steel (1018LCS) in HCl solutions was appraised by assessing weight loss, electrochemical impedance spectroscopy (EIS), and polarization at 25 °C. The maximum inhibitory efficacy for the concentration of 1 g/l of the BMRE was 92.8% at 25 °C after 2 h and increased to 95.3% after 24 h of immersion. Polarization experiments have shown that the extract in acidic solutions can act as a mixed corrosion inhibitor. The corrosion inhibitory efficacy of BMRE decreased with increasing temperature, and at all temperature settings studied, the adsorption of BMRE molecules on 1018 LCS was consistent with the Langmuir adsorption isotherm. The Scanning Electron Microscopy (SEM) analysis confirmed the protection of 1018 LCS in the acidic solution containing BMRE extract. Quantum chemistry studies of four main constituents of the extract called vasicinone, umbelliferon, scopoletin, and ferulic acid were performed by density functional theory, DFT, in neutral and protonated states. Calculated quantum parameters were used to investigate the active sites and donor-receptor interactions of molecules.

Emerging Novel Approaches for the Enhanced Delivery of Natural Products for the Management of Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington disease, amyotrophic lateral sclerosis, and prion disease affect any part of the brain. The complete mechanism of ND is unknown, but there are some molecular mechanism and chemical process. Natural compounds have better compatibility with the human body along with lesser side effects. Moreover, several studies showed that various natural compounds have significant neuroprotective, potent antioxidant, and anti-inflammatory properties, which are effective for treating the different type of ND. In ND, natural compounds act by various mechanisms such as preventing the generation of reactive oxygen species (ROS), eliminating destructed biomolecules before their accumulation affects cell metabolism, and improving the disease conditions. But due to the presence of the blood-brain barrier (BBB) layer and unfavorable pharmacokinetic properties of natural compounds, their delivery into the brain is limited. To minimize this problem and enhance drug delivery into the brain with an effective therapeutic dose, there is a need to develop a practical novel approach. The various studies showed that nanoformulations and microneedles (MN) containing natural compounds such as quercetin, curcumin, resveratrol, chrysin, piperine, ferulic acid, huperzine A, berberine, baicalein, hesperetin, and retinoic acid effectively improved many ND. In this review, the effect of such natural drug-loaded nanoformulation and MN patches on ND management is discussed, along with their merits and demerits. This review aims to introduce different novel approaches for enhancing natural drug delivery into the brain to manage various neurodegenerative diseases.

A Critical Analysis of Quercetin as the Attractive Target for the Treatment of Parkinson's Disease.

Parkinson's Disease (PD) is a multifaceted disorder with various factors suggested to play a synergistic pathophysiological role, such as oxidative stress, autophagy, pro-inflammatory events, and neurotransmitter abnormalities. While it is crucial to discover new treatments in addition to preventing PD, recent studies have focused on determining whether nutraceuticals will exert neuroprotective actions and pharmacological functions in PD. Quercetin, a flavonol-type flavonoid, is found in many fruits and vegetables and is recognised as a complementary therapy for PD. The neuroprotective effect of quercetin is directly associated with its antioxidant activity, in addition to stimulating cellular defence against oxidative stress. Other related mechanisms are activating Sirtuins (SIRT1) and inducing autophagy, in addition to induction of Nrf2-ARE and Paraoxonase 2 (PON2). Quercetin, whose neuroprotective activity has been demonstrated in many studies, unfortunately, has a disadvantage because of its poor water solubility, chemical instability, and low oral bioavailability. It has been reported that the disadvantages of quercetin have been eliminated with nanocarriers loaded with quercetin. The role of nanotechnology and nanodelivery systems in reducing oxidative stress during PD provides an indisputable advantage. Accordingly, the present review aims to shed light on quercetin's beneficial effects and underlying mechanisms in neuroprotection. In addition, the contribution of nanodelivery systems to the neuroprotective effect of quercetin is also discussed.

Can We Use mTOR Inhibitors for COVID-19 Therapy?

Infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes acute inflammation due to extensive replication of the virus in the epithelial cells of the upper and lower respiratory system. The mammalian target of rapamycin (mTOR) is a l signalling protein with critical functions in cell growth, metabolism, and proliferation. It is known for its regulatory functions in protein synthesis and angiogenesis cascades. The structure of mTOR consists of two distinct complexes (mTORC1 and mTORC2) with diverse functions at different levels of the signalling pathway. By activating mRNA translation, the mTORC1 plays a key role in regulating protein synthesis and cellular growth. On the other hand, the functions of mTORC2 are mainly associated with cell proliferation and survival. By using an appropriate inhibitor at the right time, mTOR modulation could provide immunosuppressive opportunities as antirejection regimens in organ transplantation as well as in the treatment of autoimmune diseases and solid tumours. The mTOR also has an important role in the inflammatory process. Inhibitors of mTOR might indeed be promising agents in the treatment of viral infections. They have further been successfully used in patients with severe influenza A/H1N1 pneumonia and acute respiratory failure. The officially accepted mTOR inhibitors that have undergone clinical testing are sirolimus, everolimus, temsirolimus, and tacrolimus. Thus, further studies on mTOR inhibitors for SARS-CoV-2 infection or COVID-19 therapy are well merited.

Withdrawal Notice: A New Perspective on the Treatment of Alzheimer's disease and Sleep Deprivation-related Consequences: Curcumin

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A perspective on the applications of furin inhibitors for the treatment of SARS-CoV-2.

Currently, the world is facing a pandemic of the new coronavirus SARS-CoV-2 that causes COVID-19. Identifying key targets in the viral infection lifecycle is urgently needed for designing therapeutic strategies to combat the virus. Furin is a subtilisin-like proprotein convertase with diverse cellular functions. Emerging evidence suggests that furin plays a critical role in the activation and/or infectivity of SARS-CoV-2. In this perspective, we discuss the potential role of furin in the entry SARS-CoV-2 into host cells. Furthermore, we evaluate available peptide and non-peptide furin inhibitors and potential outcomes, including immune responses.

Shaping the gut microbiota by bioactive phytochemicals: An emerging approach for the prevention and treatment of human diseases.

The human digestive tract is the cottage to trillions of live microorganisms, which regulate health and illness. A healthy Gut Microbiota (GM) is necessary for preventing microbial growth, body growth, obesity, cancer, diabetes, and enhancing immunity. The equilibrium in GM's composition and the presence/absence of critical species enable specific responses to be essential for the host's better health condition. Research evidences revealed that the dietary plants and their bioactive phytochemicals (BPs) play an extensive and critical role in shaping the GM to get beneficial health effects. BPs are also known to improve gastrointestinal health and reduce the risk of several diseases by modulating GM-mediated cellular and molecular processes. Regular intake of BPs-rich vegetables, fruits, and herbal preparations promotes probiotic bacteria, including Bifidobacteria and Lactobacillus species, while inhibiting unwanted gut residents' development Escherichia coli, and Salmonella typhimurium etc. Upon consumption, BPs contact the GM that gets transformed before being absorbed from the gastrointestinal tract. Biotransformation of BPs by GM is linked with the enhancement of bioactivity/toxicity diminishment of the BPs compared to parental phytochemicals. Therefore, the current review focuses on the role of BPs in shaping GM for the prevention and treatment of human diseases.

Himalayan Ficus palmata L. Fruit Extract Showed In Vivo Central and Peripheral Analgesic Activity Involving COX-2 and Mu Opioid Receptors.

Analgesic drugs like morphine and non-steroidal anti-inflammatory drugs exhibit several harmful effects. Here, we show for the first time the analgesic activity of Ficus palmata L. fruit extract (FPFE) on different analgesic rat models along with the in silico studies of some of the main phytochemicals of this plant. We performed in vivo pain models, along with in silico docking studies against the active site of COX-2 protein and mu-opioid receptors. A significant (p < 0.05) analgesic effect of FPFE was observed, and it was found that rutin has good pose and score as compared to diclofenac and morphinan antagonist (X-ligand), and psoralen has binding affinity almost equal to diclofenac, but a lower binding affinity as compared to rutin. The results proved that F. palmata fruits have the potential to ameliorate painful conditions.

Resveratrol and cyclodextrins, an easy alliance: Applications in nanomedicine, green chemistry and biotechnology.

Most drugs or the natural substances reputed to display some biological activity are hydrophobic molecules that demonstrate low bioavailability regardless of their mode of absorption. Resveratrol and its derivatives belong to the chemical group of stilbenes; while stilbenes are known to possess very interesting properties, these are limited by their poor aqueous solubility as well as low bioavailability in animals and humans. Among the substances capable of forming nanomolecular inclusion complexes which can be used for drug delivery, cyclodextrins show spectacular physicochemical and biomedical implications in stilbene chemistry for their possible application in nanomedicine. By virtue of their properties, cyclodextrins have also demonstrated their possible use in green chemistry for the synthesis of stilbene glucosylated derivatives with potential applications in dermatology and cosmetics. Compared to chemical synthesis and genetically modified microorganisms, plant cell or tissue systems provide excellent models for obtaining stilbenes in few g/L quantities, making feasible the production of these compounds at a large scale. However, the biosynthesis of stilbenes is only possible in the presence of the so-called elicitor compounds, the most commonly used of which are cyclodextrins. We also report here on the induction of resveratrol production by cyclodextrins or combinatory elicitation with methyljasmonate in plant cell systems as well as the mechanisms by which they are able to trigger a stilbene response. The present article therefore discusses the role of cyclodextrins in stilbene chemistry both at the physico-chemical level as well as the biomedical and biotechnological levels, emphasizing the notion of "easy alliance" between these compounds and stilbenes.

Aromatic hydrocarbon receptors in mitochondrial biogenesis and function.

Mitochondria are ubiquitous membrane-bound organelles that not only play a key role in maintaining cellular energy homeostasis and metabolism but also in signaling and apoptosis. Aryl hydrocarbons receptors (AhRs) are ligand-activated transcription factors that recognize a wide variety of xenobiotics, including polyaromatic hydrocarbons and dioxins, and activate diverse detoxification pathways. These receptors are also activated by natural dietary compounds and endogenous metabolites. In addition, AhRs can modulate the expression of a diverse array of genes related to mitochondrial biogenesis and function. The aim of the present review is to analyze scientific data available on the AhR signaling pathway and its interaction with the intracellular signaling pathways involved in mitochondrial functions, especially those related to cell cycle progression and apoptosis. Various evidence have reported the crosstalk between the AhR signaling pathway and the nuclear factor κB (NF-κB), tyrosine kinase receptor signaling and mitogen-activated protein kinases (MAPKs). The AhR signaling pathway seems to promote cell cycle progression in the absence of exogenous ligands, whereas the presence of exogenous ligands induces cell cycle arrest. However, its effects on apoptosis are controversial since activation or overexpression of AhR has been observed to induce or inhibit apoptosis depending on the cell type. Regarding the mitochondria, although activation by endogenous ligands is related to mitochondrial dysfunction, the effects of endogenous ligands are not well understood but point towards antiapoptotic effects and inducers of mitochondrial biogenesis.