Long-term growth, feed efficiency, enteric methane emission, and blood metabolite responses to in utero hyperthermia in Holstein heifers.

Dairy producers are experiencing production and animal welfare pressures from the increasing frequency and severity of heat stress events due to global climate change. Offspring performance during the preweaning and lactating periods is compromised when exposed to heat stress during late gestation (in utero). However, knowledge of the lingering effects of in utero heat stress on yearling dairy heifers is limited. Herein, we investigated the long-term effects of in utero heat stress on heifer growth, feed efficiency, and enteric methane emissions in postpubertal heifers. During the last 56 d of gestation, 38 pregnant cows carrying heifer calves were exposed to either heat stress (IUHT; n = 17) or artificial cooling (IUCL; n = 21). At 18 ± 1 mo of age, the resulting IUCL and IUHT heifers were enrolled in the present 63-d study. Heifers were blocked by weight and randomly assigned to 3 pens with Calan gates. Body weights were recorded on 3 consecutive days at the start and end of the trial and used to calculate ADG. Body condition score, hip width, body length, and chest girth were measured at the start and end of the study. All heifers were fed a TMR comprised of 46.6% oatlage, 44.6% grass/alfalfa haylage, 7.7% male-sterile corn silage, 0.3% urea, and 0.8% mineral/vitamin supplement (on a DM basis). The TMR and refusal samples were obtained daily, composited weekly, and dried to calculate DMI. During the study, each pen had access to a GreenFeed unit for 8 ± 1d to measure CH4 and CO2 gas fluxes. During the last 3 d of measuring CH4 and CO2 fluxes, fecal samples were collected, composited by animal, dried, and analyzed to calculate NDF, OM, and DM digestibility. On the last day of fecal sampling, blood samples were also collected via coccygeal venipuncture, and GC time-of-flight MS analysis was performed. Residual feed intake (RFI; predicted DMI - observed DMI), and feed conversion efficiency (FCE; DMI/ADG) were calculated to estimate feed efficiency. No differences were found in initial or final BW, hip width, chest girth, or BCS; however, IUCL heifers were longer in body length compared with IUHT heifers. Dry matter intake, ADG, RFI, and FCE were similar between IUHT and IUCL heifers. In utero heat-stressed and IUCL heifers produced similar amounts of CH4 and CO2, and no differences were found in the number of GreenFeed visits or latency to approach the GreenFeed. The concentrations of 6 blood metabolites involved in lipogenic pathways were different between in utero treatments. In conclusion, in utero heat stress does not seem to have long-term effects on feed efficiency or methane emissions during the postpubertal growing phase; however, IUCL heifers maintained a body-length advantage over their IUHT counterparts and differed in concentrations of several candidate metabolites that encourage further exploration of their potential function in key organs, such as the liver and mammary gland.

Kaempferol 3-O-Rutinoside, a Flavone Derived from Tetrastigma hemsleyanum Diels et Gilg, Reduces Body Temperature through Accelerating the Elimination of IL-6 and TNF-α in a Mouse Fever Model.

Fever is a serious condition that can lead to various consequences ranging from prolonged illness to death. Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanum) has been used for centuries to treat fever, but the specific chemicals responsible for its antipyretic effects are not well understood. This study aimed to isolate and identify the chemicals with antipyretic bioactivity in T. hemsleyanum extracts and to provide an explanation for the use of T. hemsleyanum as a Chinese herbal medicine for fever treatment. Our results demonstrate that kaempferol 3-rutinoside (K3OR) could be successfully isolated and purified from the roots of T. hemsleyanum. Furthermore, K3OR exhibited a significant reduction in rectal temperature in a mouse model of fever. Notably, a 4 µM concentration of K3OR showed more effective antipyretic effects than ibuprofen and acetaminophen. To explore the underlying mechanism, we conducted an RNA sequencing analysis, which revealed that PXN may act as a key regulator in the fever process induced by lipopolysaccharide (LPS). In the mouse model of fever, K3OR significantly promoted the secretion of IL-6 and TNF-α during the early stage in the LPS-treated group. However, during the middle to late stages, K3OR facilitated the elimination of IL-6 and TNF-α in the LPS-treated group. Overall, our study successfully identified the chemicals responsible for the antipyretic bioactivity in T. hemsleyanum extracts, and it answered the question as to why T. hemsleyanum is used as a traditional Chinese herbal medicine for treating fever. These findings contribute to a better understanding of the therapeutic potential of T. hemsleyanum in managing fever, and they provide a basis for further research and development in this field.

The protective effects of Zingiber zerumbet rhizome against fevers in rats.

The Zingiber zerumbet rhizomes are traditionally used to treat fever, and the in vitro inhibitory effect of ethyl acetate extract from Zingiber zerumbet rhizomes (EAEZZR) against DENV2 NS2B/NS3 (two non-structural proteins, NS2 and NS3 of dengue virus type 2) has been reported earlier. This study was carried out to establish an acute toxicity profile and evaluate the anti-fever (anti-pyretic) activities of EAEZZR in yeast-induced fever in rats. The major compound of EAEZZR, zerumbone, was isolated using chromatographic methods including column chromatography (CC) and preparative thin-layer chromatography (PTLC). Additionally, the structure of zerumbone was elucidated using nuclear magnetic resonance (NMR), liquid chromatography mass spectrometer-ion trap-time of flight (LCMS-IT-TOF), infrared (IR), and ultraviolet (UV) spectroscopy. The toxicity of EAEZZR was evaluated using Organization for Economic Cooperation and Development Test Guideline 425 (OECD tg-425) with minor modifications at concentrations EAEZZR of 2000 mg/kg, 3000 mg/kg, and 5000 mg/kg. Anti-fever effect was determined by yeast-induced fever (pyrexia) in rats. The acute toxicity study showed that EAEZZR is safe at the highest 5000 mg/kg body weight dose in Sprague Dawley rats. Rats treated with EAEZZR at doses of 125, 250, and 500 mg/kg exhibited a significant reduction in rectal temperature (TR) in the first 1 h. EAEZZR at the lower dose of 125 mg/kg showed substantial potency against yeast-induced fever for up to 2 h compared to 0 h in controls. A significant reduction of TR was observed in rats treated with standard drug aspirin in the third through fourth hours. Based on the present findings, ethyl acetate extract of Zingiber zerumbet rhizomes could be considered safe up to the dose of 5000 mg/kg, and the identification of active ingredients of Zingiber zerumbet rhizomes may allow their use in the treatment of fever with dengue virus infection.

Intranasal delivery of herbal medicine for disease treatment: A systematic review.

BACKGROUND: Intranasal administration has been adopted in traditional medicine to facilitate access to the bloodstream and central nervous system (CNS). In modern medicine, nasal drug delivery systems are valuable for disease treatment because of their noninvasiveness, good absorption, and fast-acting effects. OBJECTIVE: This study aimed to systematically organize preclinical and clinical studies on intranasal herbal medicines to highlight their potential in drug development. METHODS: A comprehensive search for literature until February 2023 was conducted on PubMed and the Web of Science. From the selected publications, we extracted key information, including the types of herbal materials, target diseases, intranasal conditions, methods of toxicity evaluation, main outcomes, and mechanisms of action, and performed quality assessments for each study. RESULTS: Of the 45 studies, 13 were clinical and 32 were preclinical; 28 studies used herbal extracts, 9 used prescriptions, and 8 used natural compounds. The target diseases were rhinosinusitis, influenza, fever, stroke, migraine, insomnia, depression, memory disorders, and lung cancer. The common intranasal volumes were 8-50 µl in mice, 20-100 µl in rats, and 100-500 µl in rabbits. Peppermint oil, Ribes nigrum folium, Melia azedarach L., Elaeocarpus sylvestris, Radix Bupleuri, Da Chuan Xiong Fang, Xingnaojing microemulsion, and Ginsenoside Rb1 emerged as potential candidates for rapid intranasal therapy. The in vivo toxicity assessments were based on mortality, body weight, behavioral changes, mucociliary activity, histopathology, and blood tests. Most intranasal treatments were safe, except for Cyclamen europaeum, Jasminum sambac, Punica granatum L., and violet oil, which caused mild adverse effects. At lower doses, intranasal herbal treatments often show greater effects than oral administration. The actions of intranasal herbal medicine mainly involve regulating inflammation and neurotransmission, with the olfactory bulb and anterior cingulate cortex to be relevant brain regions. CONCLUSION: Intranasal delivery of herbal materials holds promise for enhancing drug delivery efficacy and reducing treatment duration, offering a potential future perspective for developing intranasal therapies for various diseases.

Exploration of the utility of different doses of Qingfei Dayuan granules: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Clinical studies have confirmed that Qingfei Dayuan (QFDY) granules are effective in the treatment of influenza and upper respiratory tract infections (URTIs) caused by pulmonary heat-toxin syndrome (PHTS). Granules of Chinese medicine formulations have become a widely used dosage form in clinical practice. With the continuous optimization of extraction technology, the advantages of Chinese medicine granules have been gradually demonstrated, but the price of Chinese medicine granules is generally higher than that of traditional dosage forms of Chinese medicine, and we support the rational use of the appropriate dosage of QFDY for patients with these conditions. Therefore, we set up half of the conventional dose as the low dose group, and designed the three-arm study to rigorously compare the efficacy difference of low-dose QFDY, QFDY and the placebo group, with the expectation of providing scientific support for the rational selection of the dose and the safe and effective use of the medicine in clinical practice. METHODS: We recruited 108 patients with clinical diagnoses of influenza and URTIs caused by PHTS to receive treatment at six hospitals in Hubei, China. Using a centralized randomization system, patients were randomly assigned at a 1:1:1 ratio to the QFDY, low-dose QFDY, or placebo control groups to receive the corresponding drug, and the study physicians, subjects, outcome assessors, and statisticians were unaware of group assignments. The primary outcome was the time to complete fever relief. Secondary outcomes included the efficacy of Chinese medicine in alleviating signs and symptoms and the disappearance rate of individual symptoms. Adverse events were monitored throughout the trial. RESULTS: A total of 108 patients were recruited. A total of 106 patients were included in the full analysis set (FAS). In the FAS analysis, there was no statistically significant difference in baseline of the three groups before treatment (P > 0.05). 1. Regarding the median time to complete fever relief, the QFDY, low-dose QFDY and placebo groups had median times of 26 h, 40 h and 48 h, respectively. The QFDY group had a shorter time to complete fever relief than the placebo group, and the difference was statistically significant (P < 0.05), while the low-dose QFDY group had a shorter time than the placebo group, but the difference was not statistically significant (P > 0.05). 2. In terms of the total efficacy of Chinese medicine in alleviating symptoms at the end of three full days of treatment, as well as the cure rate of red and sore throat, stuffy and runny nose, and sneezing, QFDY and low-dose QFDY were superior to the placebo, and the differences were statistically significant (P < 0.01). There was no statistical significance in the comparison between the QFDY group and the low-dose QFDY group (P > 0.05). 3. In terms of the headache cure rate after three full days of treatment, QFDY was superior to the placebo, with a statistically significant difference (P < 0.05), and there was no significant efficacy of low-dose QFDY. 4. Safety comparisons showed no serious adverse events and 30 minor adverse events, which were not clinically considered to be related to the drug and were not statistically significant. CONCLUSIONS: In the treatment of patients with influenza and URTIs caused by PHTS, which are mainly characterized by clinical symptoms such as red and sore throat, stuffy and runny nose, and sneezing, when fever is not obvious or low-grade fever is present, the use of low-dose QFDY to simply alleviate the clinical symptoms is recommended and preferred. Moreover, with its good safety profile, QFDY can be used in the treatment of patients with influenza and URTIs caused by PHTS, which can effectively shorten the duration of fever, significantly increase the total efficacy of Chinese medicine in alleviating symptoms after 3 days of treatment, and accelerate the recovery of symptoms such as red and sore throat, stuffy and runny nose, sneezing, and headache, etc. Clinical Trial Registration: http://www.chictr.org.cn. TRIAL NUMBER: ChiCTR2100043449. Registered on 18 February 2021.

Antipyretic effect of inhaled Tetrastigma hemsleyanum polysaccharide on substance and energy metabolism in yeast-induced pyrexia mice via TLR4/NF-κb signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum Diels et Gilg, is one of the perennial evergreen plants with grass vine, which has obvious curative effect on severe infectious diseases. Although Tetrastigma hemleyanum has long been recognized for its capacity of antipyretic and antitoxic, its specific mechanism is unknown. AIM OF THE STUDY: To evaluate the antipyretic effect of Tetrastigma hemleyanum polysaccharide (THP) on mice with dry yeast-induced fever, and to explore its specific antipyretic mechanism. METHODS: In this study, THP was administered by aerosol in febrile mice. The rectal temperatures of treated animals were monitored at different time points. Histopathological evaluation and various inflammatory indexes were used to assess inflammatory damage. The concentration variations of the central neurotransmitter, endocrine system, substance and energy metabolism indicators were measured to explore the physiological mechanism. Quantitative real-time PCR, Western bolt and Immunohistochemistry were performed to identify the correlation between antipyretic and TLR4/NF-κB signaling pathway. RESULTS: THP reduced the body temperature of febrile mice induced by dry yeast, as well as the levels of thermogenic cytokines and downregulated the contents of thermoregulatory mediators. THP alleviated the pathological damage of liver and hypothalamus caused by fever. In addition, THP decreased the secretion of thyroid hormone, substance and energy metabolism related indicators. Furthermore, THP significantly suppressed TLR4/NF-κB signaling pathway-related indicators. CONCLUSIONS: In conclusion, our results suggest that inhaled THP exerts antipyretic effect by mediating the thermoregulatory mediator, decreasing the content of pyrogenic factors to lower the body temperature, and eventually restoring the high metabolic level in the body to normal via inhibiting TLR4/NF-κB signaling pathway. The study provides a reasonable pharmacodynamic basis for the treatment of polysaccharide in febrile-related diseases.

Fractionation and Lability of Phosphorus Species in Cottonseed Meal-Derived Biochars as Influenced by Pyrolysis Temperature.

Defatted cottonseed meal (CSM), the residue of cottonseeds after oil extraction, is a major byproduct of the cotton industry. Converting CSM to biochar and utilizing the goods in agricultural and environmental applications may be a value-added, sustainable approach to recycling this byproduct. In this study, raw CSM was transformed into biochar via complete batch slow pyrolysis at 300, 350, 400, 450, 500, 550, and 600 °C. Thermochemical transformation of phosphorus (P) in CSM during pyrolysis was explored. Fractionation, lability, and potential bioavailability of total P (TP) in CSM-derived biochars were evaluated using sequential and batch chemical extraction techniques. The recovery of feed P in biochar was nearly 100% at ≤550 °C and was reduced to <88% at 600 °C. During pyrolysis, the organic P (OP) molecules predominant in CSM were transformed into inorganic P (IP) forms, first to polyphosphates and subsequently to orthophosphates as promoted by a higher pyrolysis temperature. Conversion to biochar greatly reduced the mobility, lability, and bioavailability of TP in CSM. The biochar TP consisted of 9.3-17.9% of readily labile (water-extractable) P, 10.3-24.1% of generally labile (sequentially NaHCO3-extractable) P, 0.5-2.8% of moderately labile (sequentially NaOH-extractable) P, 17.0-53.8% of low labile (sequentially HCl-extractable) P, and 17.8-47.5% of residual (unextractable) P. Mehlich-3 and 1 M HCl were effective batch extraction reagents for estimating the "readily to mid-term" available and the "overall" available P pools of CSM-derived biochars, respectively. The biochar generated at 450 °C exhibited the lowest proportions of readily labile P and residual P compounds, suggesting 450 °C as the optimal pyrolysis temperature to convert CSM to biochar with maximal P bioavailability and minimal runoff risk.

Efficacy of Doxycycline and Ciprofloxacin for Treatment of Pneumonic Tularemia in Cynomolgus Macaques.

BACKGROUND: The incidence of pneumonic tularemia is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCMs) in humans. The US Food and Drug Administration's Animal Model Qualification Program under the Drug Development Tools Program is a regulatory pathway for animal models used in MCM efficacy testing and approval under the Animal Rule. The National Institute of Allergy and Infectious Diseases and Biomedical Advanced Research and Development Authority worked together to qualify the cynomolgus macaque model of pneumonic tularemia. METHODS: Using the model parameters and end points defined in the qualified model, efficacy of the antibiotics doxycycline and ciprofloxacin was evaluated in separate studies. Antibiotic administration, aimed to model approved human dosing, was initiated at time points of 24 hours or 48 hours after onset of fever as an indicator of disease. RESULTS: Upon aerosol exposure (target dose of 1000 colony-forming units) to Francisella tularensis SchuS4, 80% of vehicle-treated macaques succumbed or were euthanized. Ciprofloxacin treatment led to 10 of 10 animals surviving irrespective of treatment time. Doxycycline administered at 48 hours post-fever led to 10 of 10 animals surviving, while 9/10 animals survived in the group treated with doxycycline 24 hours after fever. Selected surviving animals in both the placebo and doxycycline 48-hour group showed residual live bacteria in peripheral tissues, while there were no bacteria in tissues from ciprofloxacin-treated macaques. CONCLUSIONS: Both doxycycline and ciprofloxacin were efficacious in treatment of pneumonic tularemia, although clearance of bacteria may be different between the 2 drugs.

Visceral leishmaniasis misdiagnosed as an upper respiratory infection and iron-deficiency anemia in a 20-month-old male patient: a case report.

BACKGROUND: Visceral Leishmaniasis should be suspected in every patient with a history of splenomegaly, fever, and pancytopenia. It is one of the most dangerous forms of infection and prompt recognition is the key to positive outcome. CASE PRESENTATION: A 20-month-old Caucasian male patient was brought to our hospital as an outpatient with the complaint of persistent fever, which did not improve with empiric antibiotic treatment (> 96 hour after the initial dose). The antibiotic treatment had been prescribed by primary care physician at polyclinic, who also referred the patient to hematologist due to anemia, who prescribed iron supplement. Despite multiple subspecialist visits, bicytopenia was, unfortunately, left unidentified. Upon physical examination no specific signs were detected, however, spleen seemed slightly enlarged. Patient was admitted to the hospital for further work-up, management and evaluation. Abdominal ultrasound, complete blood count and c-reactive protein had been ordered. Hematologist and infectionist were involved, both advised to run serology for Epstein-Barr Virus and Visceral Leishmaniasis. The latter was positive; therefore, patient was transferred to the specialized clinic for specific management. CONCLUSION: Both in endemic and non-endemic areas the awareness about VL should be increased among the medical professionals. We also recommend that our colleagues take the same approach when dealing with bicytopenia and fever, just as with pancytopenia and fever. The medical community should make sure that none of the cases of fever and pancytopenia are overlooked, especially if we have hepatomegaly and/or splenomegaly.

2-Hydroxybenzohydrazide as a novel potential candidate against nociception, inflammation, and pyrexia: in vitro, in vivo, and computational approaches.

The current study was designed to evaluate the 2-hydroxybenzohydrazide (HBH) as a drug having efficacy against pyrexia, inflammation, and nociception. Besides, the therapeutic effects of HBH on oxidative stress and C-reactive proteins were also evaluated. The pharmacological studies on HBH (20-60 mg/kg) were conducted using nociception, inflammation, and pyrexia standard models. Naloxone antagonism was performed to assess the possible involvement of opioidergic mechanisms. The antioxidant study was conducted on ABTS and DPPH assays using gallic acid as a standard. Moreover, the binding capability of HBH with enzymes cyclooxygenase-I/II (COX-I/II) was determined using molecular modeling analysis. The findings indicated that the HBH dose-dependently inhibited pain, inflammation, and pyrexia. The HBH has significant anti-nociceptive and anti-inflammatory activities at 60 mg/kg (***p < 0.001), similar to the lower doses of diclofenac sodium (50 mg/kg) and tramadol (30 mg/kg). The HBH at 60 mg/kg reduced pyrexia as paracetamol (150 mg/kg). The HBH at 20-60 mg/kg doses declined the plasma C-reactive protein concentration. The mechanistic studies showed that the anti-nociceptive effect of HBH was antagonized by naloxone, indicating that the opioidergic mechanisms are involved. Furthermore, computational studies showed that the HBH exhibited an affinity for COX-I/II target receptors. The HBH significantly inhibited ABTS and DPPH radicals (IC50 = 33.81 and 26.74 µg/ml). These results proposed that the HBH has significant antipyretic, anti-inflammatory, and anti-nociceptive activities involving opioidergic mechanism.

Investigation of Anti-inflammatory, Antipyretic and Analgesic Activities of Citrullus colocynthis in Albino Rats through in vivo and Pharmacoinformatics Studies.

INTRODUCTION: Hyperpyrexia, algesia and inflammation are pathological disorders which are treated with synthetic as well as herbal medications. AIMS: The basic aim of the present study is to evaluate the ethnopharmacological activities of phytoconstituents that are present in C. colocynthis (fruit extract) by using in vivo and in silico studies. METHODS: Thirty-six albino rats were used in our studies with an average weight between 150-170 g. Anti-inflammatory activity was investigated using carrageenan (an extract from a red seaweed) that induced edema in albino rat paws. However, in antipyretic and analgesic activity studies, yeast and acetic acid were used to cause pyrexia or algesia, respectively. Different doses of acetone fruit extract were used to treat inflammation, pyrexia and algesia. RESULTS: Our results showed that the maximum percentage inhibition of acetonic fruit extract in anti-inflammatory and analgesic activities was observed at 70% and 100%, respectively, with 400 mg/kg doses, and in pyretic activity the maximum inhibitory percentage was 86% with a 100 mg/kg dose. In in silico analysis, we have shown that bioactive compounds (α-spinasterol, ascorbic acid and chlorogenic acid) found in fruit extract have outstanding inhibition properties that involves proteins PTGS2, TLR2 and TRPV4. C. colocynthis fruit extract shows results that are statistically significant (p < 0.005) and comparable to a reference drug. Acetonic fruit extract of C. colocynthis can be used as a natural and safe remedy with no side effects. CONCLUSION: Both in vivo and in silico studies on chlorogenic acid, ascorbic acid and α-spinasterol have shown that these are inhibitory compounds that can be used for boosting the immune response.

Antipyretic activity of the hydro-alcoholic extract of Artemisia absinthium L. as a standalone and as an adjuvant with barley water against yeast-induced pyrexia in albino Wistar rats.

OBJECTIVES: In Unani medicine, a comprehensive treatment plan has been delineated to deal with febrile illnesses using herbal drugs along with modified dietetics, which stands as a promising area of research. The present study was aimed at evaluating the antipyretic activity of the HAE of Artemisia absinthium L. whole plant as a standalone and as an adjuvant with barley water in an animal model of pyrexia to validate the age-old Unani principle of the treatment. METHODS: The pyrexia was induced in all the groups except the plain control using Brewer's yeast. Group II did not receive any treatment, while group III received crocin, group IV received HAE of A. absinthium, group V administered Ma al-Sha'ir, and group VI was treated with the HAE of A. absinthium along with Ma al-Sha'ir by oral route. The rectal temperature of each rat was recorded at '0' h, 30 min, 60 min, and 180 min. RESULTS: The mean rectal temperature of group III went down from 101.82±0.20 °F to 100.4±0.57 °F over the period of (0-180) minutes, whereas the mean temperature in group IV went down from 102.45±0.60 °F to 100.14±0.57 °F. The mean rectal temperature of group V decreased from 100.62±0.11 °F to 99.55±0.51 °F, while the mean rectal temperature of group VI went down from 101.95±0.1 °F to 97.7±0.11 °F. CONCLUSIONS: It is concluded that the HAE of A. absinthium L. as a standalone and along with Ma al Sha'ir showed excellent antipyretic activity as compared to the standard drug in an animal model.

Subcutaneous lysophosphatidylcholine administration promotes a febrile and immune response in Holstein heifer calves.

Lysophosphatidylcholine (LPC) is immunomodulatory in nonruminants; however, the actions of LPC on immunity in cattle are undefined. Our objective was to study the effects of LPC administration on measures of immunity, liver health, and growth in calves. Healthy Holstein heifer calves (n = 46; age 7 ± 3 d) were randomly assigned to 1 of 4 treatments (n = 10 to 11 calves/treatment): a milk replacer diet unsupplemented with lecithin in the absence (CON) or presence of subcutaneously (s.c.) administered mixed (mLPC; 69% LPC-16:0, 25% LPC-18:0, 6% other) or pure LPC (pLPC; 99% LPC-18:0), or a milk replacer diet supplemented with 3% lecithin enriched in lysophospholipids containing LPC in the absence of s.c.-administered LPC (LYSO) for 5 wk. Calves received 5 s.c. injections of vehicle (10 mL of phosphate-buffered saline containing 20 mg of bovine serum albumin/mL; CON and LYSO) or vehicle containing mLPC or pLPC to provide 10 mg of total LPC per kilogram of BW per injection every 12 h during wk 2 of life. Calves were fed a milk replacer containing 27% crude protein and 24% fat at 1.75% of BW per day (dry matter basis) until wk 6 of life (start of weaning). Starter grain and water were provided ad libitum. Body measurements were recorded weekly, and clinical observations were recorded daily. Blood samples were collected weekly before morning feeding and at 0, 5, and 10 h, relative to the final s.c. injection of vehicle or LPC. Data were analyzed using a mixed model, with repeated measures including fixed effects of treatment, time, and their interaction. Dunnett's test was used to compare treatments to CON. Peak rectal temperatures were higher in mLPC or pLPC, relative to CON. Plasma LPC concentrations were greater in mLPC and LYSO calves 5 h and 10 h after the final injection, relative to CON. Calves receiving mLPC and pLPC also had higher circulating serum amyloid A concentrations, relative to CON. Calves receiving mLPC had greater serum aspartate aminotransferase, γ-glutamyltransferase, and glutamate dehydrogenase concentrations, relative to CON. Calves provided mLPC experienced lower average daily gain (ADG) after weaning, relative to CON. The LYSO treatment did not modify rectal temperatures, ADG, or measures of liver health, relative to CON. We conclude that LPC administered as s.c. injections induced an acute febrile response, modified measures of liver and immune function, and impaired growth in calves.

Network pharmacology integrated with experimental verification reveals the antipyretic characteristics and mechanism of Zi Xue powder.

CONTEXT: Zi Xue Powder (ZXP) is a traditional formula for the treatment of fever. However, the potential mechanism of action of ZXP remains unknown. OBJECTIVE: This study elucidates the antipyretic characteristics of ZXP and the mechanism by which ZXP alleviates fever. MATERIALS AND METHODS: The key targets and underlying fever-reducing mechanisms of ZXP were predicted using network pharmacology and molecular docking. The targets of ZXP anti-fever active ingredient were obtained by searching TCMSP, STITCH and HERB. Moreover, male Sprague-Dawley rats were randomly divided into four groups: control, lipopolysaccharide (LPS), ZXP (0.54, 1.08, 2.16 g/kg), and positive control (acetaminophen, 0.045 g/kg); the fever model was established by intraperitoneal LPS injection. After the fever model was established at 0.5 h, the rats were administered treatment by gavage, and the anal temperature changes of each group were observed over 10 h after treatment. After 10 h, ELISA and Western blot analysis were used to further investigate the mechanism of ZXP. RESULTS: Network pharmacology analysis showed that MAPK was a crucial pathway through which ZXP suppresses fever. The results showed that ZXP (2.16 g/kg) decreased PGE2, CRH, TNF-a, IL-6, and IL-1ß levels while increasing AVP level compared to the LPS group. Furthermore, the intervention of ZXP inhibited the activation of MAPK pathway in LPS-induced fever rats. CONCLUSIONS: This study provides new insights into the mechanism by which ZXP reduces fever and provides important information and new research ideas for the discovery of antipyretic compounds from traditional Chinese medicine.

A NEW HYPOTHESIS IN THE TREATMENT OF RECURRENT GLIOBLASTOMA MULTIFORME (GBM). PART 2: IS THERE AN ALTERNATIVE THERAPY OPTION IN RECURRENT GM WHEN ALL STANDARD TREATMENTS HAVE BEEN EXHAUSTED?

Glioblastoma multiforme (GBM) is the most aggressive and malignant brain tumor. The average survival time for a patient diagnosed with GBM, using standard treatment methods, is several months. Besides the routinely applied treatments such as neurosurgery, radiotherapy, and chemotherapy, progress is being made in the field of oncology, offering hope for improved treatment outcomes. New treatment methods include individualized multimodal immunotherapy (IMI) and modulated electro-hyperthermia. The coauthor of the above series of articles (parts 1 and 2) - A.Cz. presents the concept of a new, potentially breakthrough treatment option for recurrent GBM. A.Cz. was diagnosed with GBM in August 2021. Exhaustion of standard treatment methods, as well as immunotherapy and virotherapy, only provided temporary relief. Unfortunately, after a few months, the disease recurred. Having little to lose, A.Cz. accepted an ablative dose of 2960 MBq (80 mCi) of I131, based on available literature data. Three days before the administration of radioiodine therapy (RIT), A.Cz. prophylactically blocked the thyroid's ability to absorb the radioisotope. In June 2023, approximately 7 weeks after receiving single I131 dose, the MRI examination confirmed a 30% reduction in the tumor's size. Based on this, one can speculate that Iodine-131 therapy may be an alternative treatment option for GBM patients in the future. However, this hypothesis requires confirmation in further clinical studies.

Comparative study of antipyretic potency of extracts of morinda lucida leaves and fruits of capsicum frutescens in albino rats.

Background: Morinda lucida leaves and fruits of Capsicum frutescens are used locally in the management of fever in Nigeria. No scientific credence has been lent to this claim. Objective: To investigate the antipyretic effect and potency of aqueous extracts of Morinda lucida leaves and fruits of Capsicum frutescens in albino rats. Method: Brewer's yeast was used to induce pyrexia. Thirty animals were divided into six groups. Group A was orally administered normal saline (103 mg/kg). Group B was served indomethacin (5 mg/kg), while groups C and D received aqueous extract of Capsicum frutescens at 100mg/kg and 200mg/kg, 17 hours post induction of pyrexia. Groups E and F were administered extract of Morinda lucida at the same doses. Rectal temperature of the animals was taken at 60-, 90- and 120-minutes post-treatment. Results: Both C. frutescens and M. lucida produced significant reduction (p<0.05) in rectal temperature after 120 minutes in the rats compared with animals in the control group. Also, the antipyretic activities of the two extracts at 100mg/kg and 200mg/kg were comparable to 5mg/kg of indomethacin, with apparent dose dependence in the antipyretic activities of both extracts. Conclusion: Morinda lucida leaves and fruits of Capsicum frutescens exhibit dose-dependent antipyretic activities.

A wireless physiological parameter monitoring system with a treatment feedback function during neonatal phototherapy.

Objective. Neonatal jaundice is a common condition in the early stages of newborns, and phototherapy is a fast, safe and effective method that is used to treat it. However, recent studies have shown that phototherapy may elicit side effects in infants, such as hypothermia, hyperthermia and dehydration. To improve the quality of phototherapy and the prognosis of patients, the changes in neonatal physiological parameters during phototherapy should be monitored to give better feedback to pediatricians or the phototherapy system. However, the current standard of clinical care during neonatal phototherapy with hard-wired devices limits this realization.Approach. Here, we developed a prototype of a neonatal wearable device, which can wirelessly potentially monitor the jaundice value, transepidermal water loss, skin wettedness factor and body orientation during phototherapy, and conducted prototype validation experiments. We also set up user-friendly interfaces and an analysis system on custom software, all designed to make the future addition of data interfaces for treatment feedback functions easier.Main results. The preliminaryin vitroexperiment demonstrated the effectiveness of simultaneous monitoring of the required physiological parameters. And further suggestions and specific operations are discussed in terms of optimization of the treatment of neonatal jaundice.Significance. It is believed that the established system has the potential to provide a basis for future phototherapy nursing guidelines and physiological monitoring standards.

Clinical evidence of three traditional Chinese medicine drugs and three herbal formulas for COVID-19: A systematic review and meta-analysis of the Chinese population.

BACKGROUND: The coronavirus disease 2019 (COVID-19) continues to spread worldwide. Integrated Chinese and Western medicine have had some successes in treating COVID-19. OBJECTIVE: This study aims to evaluate the efficacy and safety of three traditional Chinese medicine drugs and three herbal formulas (3-drugs-3-formulas) in patients with COVID-19. SEARCH STRATEGY: Relevant studies were identified from 12 electronic databases searched from their establishment to April 7, 2022. INCLUSION CRITERIA: Randomized controlled trials (RCTs), non-RCTs and cohort studies that evaluated the effects of 3-drugs-3-formulas for COVID-19. The treatment group was treated with one of the 3-drugs-3-formulas plus conventional treatment. The control group was treated with conventional treatment. DATA EXTRACTION AND ANALYSIS: Two evaluators screened and selected literature independently, then extracted basic information and assessed risk of bias. The treatment outcome measures were duration of main symptoms, hospitalization time, aggravation rate and mortality. RevMan 5.4 was used to analyze the pooled results reported as mean difference (MD) with 95% confidence interval (CI) for continuous data and risk ratio (RR) with 95% CI for dichotomous data. RESULTS: Forty-one studies with a total of 13,260 participants were identified. Our analysis suggests that compared with conventional treatment, the combination of 3-drugs-3-formulas might shorten duration of fever (MD = -1.39; 95% CI: -2.19 to -0.59; P < 0.05), cough (MD = -1.57; 95% CI: -2.16 to -0.98; P < 0.05) and fatigue (MD = -1.36; 95% CI: -2.21 to -0.51; P < 0.05), decrease length of hospital stay (MD = -2.62; 95% CI -3.52 to -1.72; P < 0.05), the time for nucleic acid conversion (MD = -2.92; 95% CI: -4.26 to -1.59; P < 0.05), aggravation rate (RR = 0.49; 95% CI: 0.38 to 0.64; P < 0.05) and mortality (RR = 0.34; 95% CI: 0.19 to 0.62; P < 0.05), and increase the recovery rate of chest computerized tomography manifestations (RR = 1.22; 95% CI: 1.14 to 1.3; P < 0.05) and total effectiveness (RR = 1.24; 95% CI: 1.09 to 1.42; P < 0.05). CONCLUSION: The 3-drugs-3-formulas can play an active role in treating all stages of COVID-19. No severe adverse events related to 3-drugs-3-formulas were observed. Hence, 3-drugs-3-formulas combined with conventional therapies have effective therapeutic value for COVID-19 patients. Further long-term high-quality studies are essential to demonstrate the clinical benefits of each formula. Please cite this article as: You LZ, Dai QQ, Zhong XY, Yu DD, Cui HR, Kong YF, Zhao MZ, Zhang XY, Xu QQ, Guan ZY, Wei XX, Zhang XC, Han SJ, Liu WJ, Chen Z, Zhang XY, Zhao C, Jin YH, Shang HC. Clinical evidence of three traditional Chinese medicine drugs and three herbal formulas for COVID-19: A systematic review and meta-analysis of the Chinese population. J Integr Med. 2023; 21(5): 441-454.

Procalcitonin and C-Reactive Protein/Procalcitonin Ratio for Distinguishing between Infectious and Neoplastic Fever in Cancer Patients.

Objective: This study aims to investigate the potential of procalcitonin (PCT) levels and the C-reactive protein/procalcitonin (CRP/PCT) ratio as markers for distinguishing between infectious and neoplastic fever among febrile patients with malignant tumors. Methods: A retrospective analysis was conducted on febrile patients admitted to the hospital with malignant tumors. The patients were categorized into an infection group (67 cases) and a non-infection group (73 cases) based on the presence or absence of positive cultures. PCT levels, CRP levels, and CRP/PCT ratios were compared between the two groups. The receiver operating characteristic curve (ROC) was used to identify optimal cut-off values. Results: Data from 140 patients between January 2017 and December 2021 were extracted for analysis. Patients in the infected group showed elevated PCT levels and significantly decreased CRP/PCT ratios compared to the non-infected group (P < .01). The calculated cut-off values for distinguishing infectious and neoplastic fever were 0.52 ng/mL for PCT and 101.80 for CRP/PCT ratio. The ROC curve results revealed good sensitivity for both PCT (74.63%) and CRP/PCT (70.15%), while CRP/PCT demonstrated higher specificity (78.08%) compared to PCT (58.90%). Conclusions: PCT and CRP/PCT are both sensitive markers for identifying infection in patients with malignant tumors, with PCT showing slightly better sensitivity but lower specificity than CRP/PCT. Our findings suggest that CRP/PCT may be more valuable than PCT in distinguishing between infectious fever and neoplastic fever in cancer patients.

A Skin-Inspired Multifunctional Conductive Hydrogel with High Stretchable, Adhesive, Healable, and Decomposable Properties for Highly Sensitive Dual-Sensing of Temperature and Strain.

Developing smart hydrogels with excellent physicochemical properties and multi-sensing capabilities for various simulation of human skin's functions still remains a great challenge. Here, based on simple and convenient one-step covalent cross-linking method enhanced by dynamic RS-Ag interactions, a skin-inspired multifunctional conductive hydrogel with desirable physicochemical properties (including high stretchability, self-adhesion, self-healing, decomposition and removability) is developed for highly sensitive dual-sensing of temperature and strain. Benefiting from the synergistic action of multiple hydrogen bonds, RS-Ag bonds and S-S bonds, the gel exhibited a novel thermosensitive mechanism. The prepared hydrogels exhibited extremely high mechanical properties (maximum tensile strength of 0.35 MPa, elongation at break nearly 1800%, compressive stress over 4.43 MPa), excellent self-healing (96.82% (stress), 88.45% (temperature), 73.89% (mechanical property)), decomposition (the molecular weight after decomposition is below 700) and self-adhesion (enhanced contact with the material interface). In addition, this conductive hydrogel could also simultaneously achieve highly sensitive temperature-sensing (TCR: 10.89) and stress-sensing (GF: 1.469). As a proof-to-concept, the hydrogel displayed superior capability for simulation of human skin to perception of touch, pressure and ambient temperature simultaneously, indicating promising applications in the fields of wearable devices, personal health care, and human-machine interfaces.