Even though tardive dyskinesiaand also akathisia, which it resemblesare serious and horrible harms of psychiatric drugs, they are often overlooked or deliberately ignored by psychiatrists.

It took psychiatry 20 years to recognise tardive dyskinesia as an iatrogenic illness, even though it affects about 4-5% of the patients receiving neuroleptics per year. Poul Leber from the FDA concluded in 1984 that, over a lifetime, all patients might develop tardive dyskinesia. Three years later, the president of the American Psychiatric Association said on an Oprah Winfrey show that tardive dyskinesia was not a serious or frequent problem.

Neurologists are much better at spotting tardive dyskinesia than psychiatrists and the same applies to researchers. Researchers found tardive dyskinesia in 10 of 48 patients consecutively admitted with acute psychosis and treated for at least a week with neuroleptics, while the psychiatrists only made this diagnosis in one of them.

Akathisia is also common but is also often missed, ignored or misinterpreted. In the same study, the researchers diagnosed akathisia in 27 patients, the clinicians only in 7. In a community sample of patients with schizophrenia, the prevalence was 19%.

Tardive dyskinesia is an involuntary drug-induced movement disorder characterised by repetitive purposeless movements. It can have many manifestations, including fa...

The amount of energy needed to refute bullshit is an order of magnitude bigger than that needed to produce it.

While people are aware of the health risk caused by outdoor air pollution, few may consider that indoor air quality can also have a negative impact on their health. While many of these products are commonly used in the home there are healthier options available.

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Throughout the pandemic and beyond, youve likely heard top political figures and Big Tech leaders talking about the opportunity to reset and build back better. Founder and executive chairman of the World Economic Forum (WEF) Klaus Schwab is often said to be the mastermind behind this and is credited with circulating the idea of The Great Reset, of which build back better is an integral part.

However, there are other nefarious players who may have even more power, namely the newly crowned King Charles III.

When The Great Reset was officially launched in 2020, it was not done so by Klaus Schwab or Bill Gates, but by Charles, Prince of Wales, then heir-apparent to the British throne, according to Winter Oak, an independent not-for-profit organization development agenda and a commitment to truth, freedom and social justice.¹

Theyve outlined key details on why King Charles should be on your radar when it comes to the implantation of The Great Reset and Agenda 21 (Agenda for the 21st Century) the inventory and control plan for all land, water, minerals, plants, animals, construction, means of production, food, energy, information, education and all human beings in the world.

Is King Charles The Great Resetter?

In June 2020, King Charles, then The Prince of Wales, announced he was launching a new global initiative, The Great Reset, along with WEFs and His Royal Highness Sustainable Markets Initiative.² A tweet from Clarence House stated:³

#TheGreatReset initiative is designed to ensure businesses and communities build back better by putting sustainable business practices at the heart of their operations as they begin to recover from the coronavirus pandemic.

Winter Oak explained:⁴

This may come as a bit of a surprise to those who see Charles as a bumbling but affable figure, who talks to his plants, loves traditional architecture, protects nature and tries to help young people get along in life. But the reality is that he is the head (or the very willing figurehead) of a vast empire of nefarious financial interests hiding hypocritically behind a facade of charitable philanthropy.

King Charles charitable enterprise spans a ...

Editor's Note: This article is a reprint. It was originally published April 7, 2013.

Orofacial myofunctional therapy is a profoundly useful treatment that may help treat the symptoms of a wide variety of health issues, from opening airways to headaches, temporomandibular joint disorders (TMJ), to poor digestion, just to name a few. It may be the most profound therapy available for the treatment of mild to moderate sleep apnea, which is a pervasive problem that affects many.

Myofunctional therapy is the "neuromuscular re-education or repatterning of the oral and facial muscles."¹

The therapy includes facial and tongue exercises and behavior modification techniques to promote proper tongue position, improved breathing, chewing, and swallowing. Proper head and neck postures are also addressed. There are good studies to substantiate that it may resolve jaw problems and orthodontic relapse working in a multidisciplinary team.

It may also be an alternative or adjunctive treatment to facial plastic surgery, to help get rid of lines and saggy facial muscles, which is exciting. In fact, in Brazil, some myofunctional therapists work with plastic surgeons.

Joy Moeller, whom I had the good fortune of meeting as a result of an earlier interview with Carol Vander-Stoep (author of the book "Mouth Matters; How Your Mouth Ages Your Body and What YOU Can Do About It"), is a leading expert in this form of therapy in the U.S.

At the end of that interview with Vander-Stoep, we discussed the issue of being "tongue tied," and she happened to look into my mouth. A large population of Americans are estimated to have health problems related to poor orofacial function, and the vast majority have no idea their problems stem from the dysfunction of their mouth (primarily the tongue), breathing habits, and forward head and neck muscle function. It turns out I was one of them.

As a result, I got on a treatment plan with Moeller, who is a premier expert on myofunctional therapy in the U.S. We did regular Skype sessions for several months, and not only did I make great progress in resolving my tongue tie, but it had a profoundly beneficial effect on my posture and amount of deep sleep as well.

Of course, adult problems associated with tongue-tie are best prevented in infancy beginning with ensuring the normal duration of breastfeeding. However, tongue-tie often goes undetected by OBGYNs and pediatricians who, having been educated in a bottle-feeding culture, fail to connect the related breastfeeding issues.

When feeding issues are present, such as recurring maternal pain, thrush or mastitis, poor latch, inefficient emptying of the breast,...

Rendered animal fats, a byproduct of raising animals on concentrated animal feeding operations (CAFOs), are commonly added to pet food and personal care products like soap and cosmetics. However, theyre also a growing part of "sustainable aviation fuels" (SAF), to the extent that theres not enough to go around.

A study conducted by Cerulogy for Transport & Environment (T&E) revealed increasing pressure on animal fat supplies as its use in biodiesel has skyrocketed 40-fold since 2006.¹

8,800 Dead Pigs to Fuel One Transatlantic Flight

Animal fats are being touted as the latest sustainable biofuel, but as usage grows its already appearing to be an unsustainable fuel source. According to the T&E report, demand for animal fats for biofuel may triple from 2021 to 2030.² However, in Europe, 46% of animal fat feedstocks are already used as biodiesel, suggesting supply wont keep up with demand.

The study calculated that to fuel one transatlantic flight from Paris to New York, 8,800 dead pigs are needed for one way. In the European Union, animal fats are categorized into three groups depending on their risk levels for disease transmission. While categories 1 and 2 can only be used for heating, category 3 can be used in a wider range of applications, including pet food, oleochemical industries and biofuel.

With biofuel creating more demand for those category 3 fats, other industries may be pushed out of the market or find products being made with animal-fat substitutes, which are usually cheaper available oils.³ Nicole Paley, deputy chief executive of UK Pet Food, told BBC:⁴

"These [animal fats] are really valuable ingredients for us and they are hard to replace, and they're put to good use already in a very sustainable way So actually diverting these ingredients to biofuels is actually creating another problem. It would put us in competition with the aviation industry. And when it comes to the purse strings of the aviation sector, the pet food industry would find it really difficult to compete."

Dickon Posnett from Argent Energy, which produces biodiesel from wastes, added, "If you make a big incentive for use of these lipids, animal fats, and used cooking oils, in aviation, it will inevitably take it away from other things. So if you want to increase aviation sustainability, at the expense of truck sustainability, then crack on. But that's a decision for the government to make."⁵

UK Considers Ban on Animal Fats in Aviatio...

The Skeptical Raptor, stalking pseudoscience in the internet jungle.

New research shows that the risk of Guillain-Barr syndrome after receiving COVID-19 mRNA vaccines is the same as unvaccinated individuals.

Skeptical Raptor

PMID:  Zhongguo Zhong Yao Za Zhi. 2023 Mar ;48(5):1176-1185. PMID: 37005801 Abstract Title:  [Protective mechanism of salvianolic acid B on blood vessels]. Abstract:  Salvianolic acid B(Sal B) is the main water-soluble component of Salvia miltiorrhiza Bunge. Studies have found that Sal B has a good protective effect on blood vessels. Sal B can protect endothelial cells by anti-oxidative stress, inducing autophagy, inhibiting endoplasmic reticulum stress(ERS), inhibiting endothelial inflammation and adhesion molecule expression, inhibiting endothelial cell permeability, anti-thrombosis, and other ways. In addition, Sal B can alleviate endothelial cell damage caused by high glucose(HG). For vascular smooth muscle cell(VSMC), Sal B can reduce the synthesis and secretion of inflammatory factors by inhibiting cyclooxygenase. It can also play a vasodilatory role by inhibiting Ca~(2+) influx. In addition, Sal B can inhibit VSMC proliferation and migration, thereby alleviating vascular stenosis. Sal B also inhibits lipid deposition in the subendothelium, macrophage apoptosis, thereby reducing the volume of subendothelial lipid plaques. For some atherosclerosis(AS) complications, such as peripheral artery disease(PAD), Sal B can promote angiogenesis, thereby improving ischemia. It should be pointed out that the conclusions obtained from different experiments are not completely consistent, which needs further research. In addition, previous pharmacokinetics showed that Sal B was poorly absorbed by oral administration, and it was unstable in the stomach, with a large first-pass effect in the liver. Sal B had fast distribution and metabolism in vivo and short drug action time. These affect the bioavailability and biological effects of Sal B, and the development of clinically valuable Sal B non-injectable delivery systems remains a great challenge.

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PMID:  J Biochem Mol Toxicol. 2023 Apr 3:e23352. Epub 2023 Apr 3. PMID: 37010041 Abstract Title:  Chlorogenic acid protective effects on paraquat-induced pulmonary oxidative damage and fibrosis in rats. Abstract:  Paraquat (PQ) is a widely used herbicide that can cause severe oxidative and fibrotic injuries in lung tissue. Due to the antioxidant and anti-inflammatory properties of chlorogenic acid (CGA), the present study investigated its effects on PQ-induced pulmonary toxicity. To this end, 30 male rats were randomly categorized into five groups of six. Initially, the first and third groups were treated intraperitoneally (IP) with normal saline and CGA (80mg/kg) for 28 consecutive days, respectively. The second, fourth, and fifth groups were treated with normal saline and 20 and 80mg/kg of CGA for 28 consecutive days, respectively, and received a single dose of PQ (IP, 20mg/kg) on Day 7. Then, the animals were anesthetized with ketamine and xylazine, and lung tissue samples were collected for biochemical and histological examinations. The results showed that PQ significantly increased hydroxyproline (HP) and lipid peroxidation (LPO) and decreased the lung tissue antioxidant capacity. In addition, myeloperoxidase (MPO) activity increased significantly, while glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) activity declined substantially. The administration of therapeutic doses of CGA could prevent the oxidative, fibrotic, and inflammatory effects of PQ-induced lung toxicity, and these changes were consistent with histological observations. In conclusion, CGA may improve the antioxidant defense of lung tissue and prevent the spread of inflammation and the development of PQ-induced fibrotic injuries by enhancing antioxidant enzymes and preventing inflammatory cell infiltration.

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PMID:  Iran J Basic Med Sci. 2023 Apr ;26(4):478-485. PMID: 37009010 Abstract Title:  Chlorogenic acid attenuates liver apoptosis and inflammation in endoplasmic reticulum stress-induced mice. Abstract:  OBJECTIVES: The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER)results in a state known as "ER stress". It can affect the fate of proteins and play a crucial role in the pathogenesis of several diseases. In this study, we investigated the protective effect of chlorogenic acid (CA) on the inflammation and apoptosis of tunicamycin-induced ER stress in mice.MATERIALS AND METHODS: We categorized mice into six groups: Saline, Vehicle, CA, TM, CA 20-TM, and CA 50-TM. The mice received CA (20 or 50 mg/kg) before intraperitoneal tunicamycin injection. After 72 hr of treatment, serum biochemical analysis, histopathological alterations, protein and/or mRNA levels of steatosis, and inflammatory and apoptotic markers were investigated by ELISA and/or RT-PCR.RESULTS: We found that 20 mg/kg CA decreased mRNA levels of, and. Moreover, CA supplementation prevented TM-induced liver injury through changes in lipid accumulation and lipogenesis markers of steatosis (), and exerted an inhibitory effect on inflammatory (and) and apoptotic markers (caspase 3,,, and), of liver tissue in ER stress mice.CONCLUSION: These data suggest that CA ameliorates hepatic apoptosis and inflammation by reducing NF-B and Caspase 3 as related key factors between inflammation and apoptosis.

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PMID:  Pharmaceuticals (Basel). 2023 Feb 22 ;16(3). Epub 2023 Feb 22. PMID: 36986437 Abstract Title:  TLR4/Inflammasomes Cross-Talk and Pyroptosis Contribute to N-Acetyl Cysteine and Chlorogenic Acid Protection against Cisplatin-Induced Nephrotoxicity. Abstract:  BACKGROUND: Cisplatin (Cp) is an antineoplastic agent with a dose-limiting nephrotoxicity. Cp-induced nephrotoxicity is characterized by the interplay of oxidative stress, inflammation, and apoptosis. Toll-4 receptors (TLR4) and NLPR3 inflammasome are pattern-recognition receptors responsible for activating inflammatory responses and are assigned to play a significant role with gasdermin (GSDMD) in acute kidney injuries. N-acetylcysteine (NAC) and chlorogenic acid (CGA) have documented nephroprotective effects by suppressing oxidative and inflammatory pathways. Therefore, the current study aimed to investigate the contribution of the upregulation of TLR4/inflammasomes/gasdermin signaling to Cp-induced nephrotoxicity and their modulation by NAC or CGA.METHODS: A single injection of Cp (7 mg/kg, i.p.) was given to Wistar rats. Rats received either NAC (250 mg/kg, p.o.) and/or CGA (20 mg/kg, p.o.) one week before and after the Cp injection.RESULTS: Cp-induced acute nephrotoxicity was evident by the increased blood urea nitrogen and serum creatinine and histopathological insults. Additionally, nephrotoxicity was associated with increased lipid peroxidation, reduced antioxidants, and elevated levels of inflammatory markers (NF-B and TNF-) in the kidney tissues. Moreover, Cp upregulated both TLR4/NLPR3/interleukin-1beta (IL-1) and caspase-1/GSDMD-signaling pathways, accompanied by an increased Bax/BCL-2 ratio, indicating an inflammatory-mediated apoptosis. Both NAC and/or CGA significantly corrected these changes.CONCLUSIONS: This study emphasizes that inhibition of TLR4/NLPR3/IL-1/GSDMD might be a novel mechanism of the nephroprotective effects of NAC or CGA against Cp-induced nephrotoxicity in rats.

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PMID:  Poult Sci. 2023 May ;102(5):102623. Epub 2023 Mar 4. PMID: 36972676 Abstract Title:  Effects of dietary chlorogenic acid on intestinal barrier function and the inflammatory response in broilers during lipopolysaccharide-induced immune stress. Abstract:  Immune stress exerts detrimental effects on growth performance and intestinal barrier function during intensive animal production with ensuing serious economic consequences. Chlorogenic acid (CGA) is used widely as a feed additive to improve the growth performance and intestinal health of poultry. However, the effects of dietary CGA supplementation on amelioration of the intestinal barrier impairment caused by immune stress in broilers are unknown. This study investigated the effects of CGA on growth performance, intestinal barrier function, and the inflammatory response in lipopolysaccharide (LPS) mediated immune-stressed broilers. Three hundred and twelve 1-day-old male Arbor Acres broilers were divided randomly into 4 groups with 6 replicates of thirteen broilers. The treatments included: i) saline group: broilers injected with saline and fed with basal diet; ii) LPS group: broilers injected with LPS and fed with basal diet; iii) CGA group: broilers injected with saline and feed supplemented with CGA; and iv) LPS+CGA group: broilers injected with LPS and feed supplemented with CGA. Animals in the LPS and LPS+CGA groups were injected intraperitoneally with an LPS solution prepared with saline from 14 d of age for 7 consecutive days, whereas broilers in the other groups were injected only with saline. LPS induced a decrease in feed intake of broilers during the stress period, but CGA effectively alleviated this decrease. Moreover, CGA inhibited the reduction of villus height and improved the ratio of villus height to crypt depth in the duodenum of broilers 24 and 72 h after LPS injection. In addition, dietary CGA supplementation significantly restored the expression of cation-selective and channel-forming Claudin2 protein 2 h after LPS injection in the ileum. LPS enhanced the expression of tumor necrosis factor-(TNF-) and interleukin-1(IL-1) in the small intestine, but this enhancement was blocked by CGA supplementation. The expression of interleukin-10 (IL-10) increased with LPS injection and CGA promoted the production of IL-10. CGA addition downregulated the expression of intestinal interleukin-6 (IL-6) of broilers under normal rearing conditions. However, CGA supplementation upregulated the expression of IL-6 of broilers 72 h after LPS injection. The data demonstrate that dietary supplementation with CGA alleviates intestinal barrier damage and intestinal inflammation induced by LPS injection during immune stress thereby improving growth performance of broilers.

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PMID:  Chem Biol Interact. 2023 May 1 ;376:110461. Epub 2023 Mar 23. PMID: 36965689 Abstract Title:  Chlorogenic acid ameliorated non-alcoholic steatohepatitis via alleviating hepatic inflammation initiated by LPS/TLR4/MyD88 signaling pathway. Abstract:  Non-alcoholic steatohepatitis (NASH) is a severe pathological stage in non-alcoholic fatty liver disease (NAFLD) and is generally recognized to be induced by chronic inflammation. Natural compound chlorogenic acid (CGA) is well-known for its anti-inflammatory capacity. This study aimed at evaluating the alleviation of CGA on NASH and further exploring its engaged mechanism via focusing on abrogating hepatic inflammation. Our results showed that CGA had a good amelioration on NASH in vivo. CGA alleviated liver oxidative injury by inducing nuclear factor erythroid 2-related factor 2 (Nrf2) activation and reduced liver steatosis via up-regulating peroxisome proliferator-activated receptor-alpha (PPAR). CGA attenuated hepatic inflammation in vivo, but didn't decrease the elevated lipopolysaccharide (LPS) content. CGA blocked the activation of nuclear factor kappa-B (NFB) or inflammasome both in MCDD-fed mice and in LPS-stimulated macrophages. CGA was found to directly bind to myeloid differentiation primary response 88 (MyD88), and thus competitively blocked the interaction between toll-like receptor 4 (TLR4) and MyD88, thereby abrogating hepatic inflammation initiated by LPS-TLR4-MyD88. Moreover, the CGA-provided anti-inflammatory effect was obviously disappeared in macrophages overexpressed MyD88. Hence, CGA has an excellent efficacy in improving NASH. CGA alleviated liver inflammation during NASH progression through blocking LPS-TLR4-MyD88 signaling pathway via directly binding to MyD88.

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PMID:  Clin Sci (Lond). 2023 May 31 ;137(10):785-805. PMID: 36951146 Abstract Title:  Targeting TLR4/3 using chlorogenic acid ameliorates LPS+POLY I:C-induced acute respiratory distress syndrome via alleviating oxidative stress-mediated NLRP3/NF-B axis. Abstract:  Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a life-threatening condition caused due to significant pulmonary and systemic inflammation. Chlorogenic acid (CGA) has been shown to possess potent antioxidant, anti-inflammatory, and immunoprotective properties. However, the protective effect of CGA on viral and bacterial-induced ALI/ARDS is not yet explored. Hence, the current study is aimed to evaluate the preclinical efficacy of CGA in lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (POLY I:C)-induced ALI/ARDS models in vitro and in vivo. Human airway epithelial (BEAS-2B) cells exposed to LPS+POLY I:C significantly elevated oxidative stress and inflammatory signaling. Co-treatment with CGA (10 and 50M) prevented inflammation and oxidative stress mediated by TLR4/TLR3 and NLRP3 inflammasome axis. BALB/c mice, when chronically challenged with LPS+POLY I:C showed a significant influx of immune cells, up-regulation of pro-inflammatory cytokines, namely: IL-6, IL-1, and TNF-, and treatment with intranasal CGA (1 and 5 mg/kg) normalized the elevated levels of immune cell infiltration as well as pro-inflammatory cytokines. D-Dimer, the serum marker for intravascular coagulation, was significantly increased in LPS+ POLY I:C challenged animals which was reduced with CGA treatment. Further, CGA treatment also has a beneficial effect on the lung and heart, as shown by improving lung physiological and cardiac functional parameters accompanied by the elevated antioxidant response and simultaneous reduction in tissue damage caused by LPS+POLY I:C co-infection. In summary, these comprehensive, in vitro and in vivo studies suggest that CGA may be a viable therapeutic option for bacterial and viral-induced ALI-ARDS-like pathology.

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PMID:  J Mater Chem B. 2023 Mar 22 ;11(12):2663-2673. Epub 2023 Mar 22. PMID: 36883900 Abstract Title:  A chlorogenic acid functional strategy of anti-inflammation, anti-coagulation and promoted endothelial proliferation for bioprosthetic artificial heart valves. Abstract:  Heart valve replacement has become an optimal choice for the treatment of severe heart valve disease. At present, most commercial bioprosthetic heart valves (BHVs) are made from porcine pericardium or bovine pericardium treated with glutaraldehyde. Nevertheless, due to the toxicity of residual aldehyde groups left after glutaraldehyde cross-linking, these commercial BHVs exhibit poor biocompatibility, calcification, risk of coagulation and endothelialization difficulty, which greatly affects the durability of the BHVs and shortens their service life. In this work, based on a chlorogenic acid functional anti-inflammation, anti-coagulation and endothelialization strategy and dual-functional non-glutaraldehyde cross-linking reagent OX-CO, a kind of functional BHV material OX-CA-PP has been developed from OX-CO cross-linked porcine pericardium (OX-CO-PP) followed by the convenient modification of chlorogenic acid through a reactive oxygen species (ROS) sensitive borate ester bond. The functionalization of chlorogenic acid can reduce the risk of valve leaf thrombosis and promote endothelial cell proliferation, which is beneficial to the formation of a long-term interface with good blood compatibility. Meanwhile, such a ROS responsive behavior can trigger intelligent release of chlorogenic acid on-demand to achieve the inhibition of acute inflammation at the early stage of implantation. Theandexperimental results show that the functional BHV material OX-CA-PP exhibits superior anti-inflammation, improved anti-coagulation, minimal calcification and promoted proliferation of endothelial cells, showing that this non-glutaraldehyde functional strategy has great potential for the application of BHVs and providing a promising reference for other implanted biomaterials.

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PMID:  Heliyon. 2023 Mar ;9(3):e13917. Epub 2023 Feb 18. PMID: 36873494 Abstract Title:  Chlorogenic acid rich in coffee pulp extract suppresses inflammatory status by inhibiting the p38, MAPK, and NF-B pathways. Abstract:  Coffee pulp (CP) is a coffee byproduct that contains various active ingredients, namely, chlorogenic acid (CGA) and caffeine. These active compounds show several benefits, including antihyperlipidemia, antioxidants, and anti-inflammation. However, the anti-inflammatory properties of Coffea pulp extract (CPE) are unknown. This work determined the impact of CPE on lipopolysaccharide (LPS)-activated murine macrophage cells and the molecular mechanism behind this action. RAW 264.7 cells were exposed to varying doses of CPE with or without LPS. Inflammatory markers and their mechanism were studied. CPE therapy has been shown to suppress the synthesis of inflammatory cytokines and mediators, namely, tumor necrosis factor-alpha (TNF-), interleukin-6 (IL-6), IL-1, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO), as well as prostaglandin E2 (PGE). Finally, CPE inactivated the nuclear factor-kappa B (NF-B) and MAPK signaling pathways. Consequently, CPE might be used as a nutraceutical to treat inflammation and its related disorders.

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PMID:  ACS Omega. 2023 Mar 28 ;8(12):11261-11266. Epub 2023 Mar 13. PMID: 37008141 Abstract Title:  E-Cigarette Liquids and Aldehyde Flavoring Agents Inhibit CYP2A6 Activity in Lung Epithelial Cells. Abstract:  Certain e-liquids and aromatic aldehyde flavoring agents were previously identified as inhibitors of microsomal recombinant CYP2A6, the primary nicotine-metabolizing enzyme. However, due to their reactive nature, aldehydes may react with cellular components before reaching CYP2A6 in the endoplasmic reticulum. To determine whether e-liquid flavoring agents inhibited CYP2A6 in a cellular system, we investigated their effects on CYP2A6 using BEAS-2B cells transduced to overexpress CYP2A6. We demonstrated that two e-liquids and three aldehyde flavoring agents (cinnamaldehyde, benzaldehyde, and ethyl vanillin) exhibited dose-dependent inhibition of cellular CYP2A6.

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PMID:  Front Immunol. 2023 ;14:1076772. Epub 2023 Mar 14. PMID: 36999019 Abstract Title:  Aerosolized nicotine from e-cigarettes alters gene expression, increases lung protein permeability, and impairs viral clearance in murine influenza infection. Abstract:  E-cigarette use has rapidly increased as an alternative means of nicotine delivery by heated aerosolization. Recent studies demonstrate nicotine-containing e-cigarette aerosols can have immunosuppressive and pro-inflammatory effects, but it remains unclear how e-cigarettes and the constituents of e-liquids may impact acute lung injury and the development of acute respiratory distress syndrome caused by viral pneumonia. Therefore, in these studies, mice were exposed one hour per day over nine consecutive days to aerosol generated by the clinically-relevant tank-style Aspire Nautilus aerosolizing e-liquid containing a mixture of vegetable glycerin and propylene glycol (VG/PG) with or without nicotine. Exposure to the nicotine-containing aerosol resulted in clinically-relevant levels of plasma cotinine, a nicotine-derived metabolite, and an increase in the pro-inflammatory cytokines IL-17A, CXCL1, and MCP-1 in the distal airspaces. Following the e-cigarette exposure, mice were intranasally inoculated with influenza A virus (H1N1 PR8 strain). Exposure to aerosols generated from VG/PG with and without nicotine caused greater influenza-induced production in the distal airspaces of the pro-inflammatory cytokines IFN-, TNF, IL-1, IL-6, IL-17A, and MCP-1 at 7 days post inoculation (dpi). Compared to the aerosolized carrier VG/PG, in mice exposed to aerosolized nicotine there was a significantly lower amount of Mucin 5 subtype AC (MUC5AC) in the distal airspaces and significantly higher lung permeability to protein and viral load in lungs at 7 dpi with influenza. Additionally, nicotine caused relative downregulation of genes associated with ciliary function and fluid clearance and an increased expression of pro-inflammatory pathways at 7 dpi. These results show that (1) the e-liquid carrier VG/PG increases the pro-inflammatory immune responses to viral pneumonia and that (2) nicotine in an e-cigarette aerosol alters the transcriptomic response to pathogens, blunts host defense mechanisms, increases lung barrier permeability, and reduces viral clearance during influenza infection. In conclusion, acute exposure to aerosolized nicotine can impair clearance of viral infection and exacerbate lung injury, findings that have implications for the regulation of e-cigarette products.

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PMID:  Surgery. 2023 Jun ;173(6):1452-1462. Epub 2023 Mar 29. PMID: 36997424 Abstract Title:  The implications of vaping on surgical wound healing: A systematic review. Abstract:  BACKGROUND: E-cigarette use is rapidly growing, and little is known about the postoperative complications. Cigarette smoking has been well-established to be associated with delayed wound healing and increased complications in surgical patients. Due to the intricate and harmonious nature of the wound-healing process, vaping may impair tissue regeneration, posing a risk for patients undergoing surgery. This systematic review aimed to review the evidence on the implications of vaping on wound healing.METHODS: A systematic search of PubMed and Scopus databases was conducted on October 2022 per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The following keywords were used to conduct the search: vaping, vape, e-cigarettes, electronic cigarettes, wound healing, tissue regeneration, postoperative complications, wound infection, and blood flow.RESULTS: Of 5,265 screened articles, only 37 were eligible for qualitative synthesis. A total of 18 articles studied the effect of e-cigarettes on human volunteers, 14 investigated e-cigarette extract on human cell lines, and 5 used animal rat models.CONCLUSION: Despite limited objective data, the recommendation is that e-cigarettes be treated as tobacco cigarettes; hence, vaping should be stopped in the perioperative period to decrease the incidence of wound healing complications. Clinical trials are required to understand the health hazards of e-cigarettes further and maximize patient safety and clinical outcomes.

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PMID:  Lung Cancer. 2023 May ;179:107180. Epub 2023 Mar 22. PMID: 36989612 Abstract Title:  Flavored E-cigarette product aerosols induce transformation of human bronchial epithelial cells. Abstract:  OBJECTIVES: E-cigarettes are the most commonly used nicotine containing products among youth. In vitro studies support the potential for e-cigarettes to cause cellular stress in vivo; however, there have been no studies to address whether exposure to e-liquid aerosols can induce cell transformation, a process strongly associated with pre-malignancy. We examined whether weekly exposure of human bronchial epithelial cell (HBEC) lines to e-cigarette aerosols would induce transformation and concomitant changes in gene expression and promoter hypermethylation.MATERIALS AND METHODS: An aerosol delivery system exposed three HBEC lines to unflavored e-liquid with 1.2% nicotine, 3 flavored products with nicotine, or the Kentucky reference cigarette once a week for 12 weeks. Colony formation in soft agar, RNA-sequencing, and the EPIC Beadchip were used to evaluate transformation, genome-wide expression and methylation changes.RESULTS: Jamestown e-liquid aerosol induced transformation of HBEC2 and HBEC26, while unflavored and Blue Pucker transformed HBEC26. Cigarette smoke aerosol transformed HBEC4 and HBEC26 at efficiencies up to 3-fold greater than e-liquids. Transformed clones exhibited extensive reprogramming of the transcriptome with common and distinct gene expression changes observed between the cigarette and e-liquids. Transformation by e-liquids induced alterations in canonical pathways implicated in lung cancer that included axonal guidance and NRF2. Gene methylation, while prominent in cigarette-induced transformed clones, also affected hundreds of genes in HBEC2 transformed by Jamestown. Many genes with altered expression or epigenetic-mediated silencing were also affected in lung tumors from smokers.CONCLUSIONS: These studies show that exposure to e-liquid aerosols can induce a pre-malignant phenotype in lung epithelial cells. While the Food and Drug Administration banned the sale of flavored cartridge-based electric cigarettes, consumers switched to using flavored products through other devices. Our findings clearly support expanding studies to evaluate transformation potency for the major categories of e-liquid flavors to better inform risk from these complex mixtures.

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