Lower incidence of COVID-19 in patients with inflammatory bowel disease treated with non-gut selective biologic therapy.

BACKGROUND AND AIM: Since the outbreak of COVID-19, concerns have been raised as to whether inflammatory bowel disease (IBD) patients under biologic therapy may be more susceptible to the disease. This study aimed to determine the incidence and outcomes of COVID-19 in a large cohort of IBD patients on biologic therapy. METHODS: This observational retrospective multicenter study collected data about COVID-19 in IBD patients on biologic therapy in Italy, between February and May 2020. The main end-points were (i) to assess both the cumulative incidence and clinical outcome of COVID-19, according to different biologic agents and (ii) to compare them with the general population and a cohort IBD patients undergoing non-biologic therapies. RESULTS: Among 1816 IBD patients, the cumulative incidence of COVID-19 was 3.9 per 1000 (7/1816) with a 57% hospitalization rate and a 29% case-fatality rate. The class of biologic agents was the only risk factor of developing COVID-19 (P = 0.01). Non-gut selective agents were associated with a lower incidence of COVID-19 cases, related symptoms, and hospitalization (P < 0.05). Compared with the general population of Lombardy, an overall lower incidence of COVID-19 was observed (3.9 vs 8.5 per 1000, P = 0.03). Compared with 565 IBD patients on non-biologic therapies, a lower rate of COVID-19 symptoms was observed in our cohort (7.5% vs 18%, P < 0.001). CONCLUSIONS: Compared with the general population, IBD patients on biologic therapy are not exposed to a higher risk of COVID-19. Non-gut selective agents are associated with a lower incidence of symptomatic disease, supporting the decision of maintaining the ongoing treatment.

In vitro cultured calculus bovis attenuates cerebral ischaemia-reperfusion injury by inhibiting neuronal apoptosis and protecting mitochondrial function in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In vitro cultured calculus bovis (ICCB), which is produced based on the formation mechanism of bovine gallstones, is used to replace the natural bezoar. It has been used in the clinic to treat brain diseases, including stroke, Alzheimer's disease and depression. AIM OF STUDY: ICCB is used to treat encephalopathy in the clinic. We explored the effects of ICCB on cerebral ischaemia-reperfusion injury (CIRI) and the potential associated mechanisms. MATERIALS AND METHODS: Rats were subjected to middle cerebral artery occlusion for 90 min, followed by 24 h of reperfusion, after being given different concentrations of ICCB once a day for 3 days. Subsequently, the neurological scores, brain oedema and volume of cerebral infarction were measured, and the histopathological changes in the cortex neurons were observed by haematoxylin and eosin staining (H&E). Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL). Ultrastructural changes in the mitochondria of the cortex were assessed by transmission electron microscopy (TEM). The apoptosis-related proteins Bax, Bcl-2, caspase-9, caspase-3, Mito-Cyt C and Cyto-Cyt C were detected by Western blotting. RESULTS: Compared with those in the control group, the neurological scores, the volumes of cerebral infarction, and the brain water contents were significantly decreased in the ICCB groups at doses of 50 and 100 mg/kg. The ICCB treatment effectively decreased the neuronal apoptosis resulting from the CIRI-induced neuron injury. In addition, the histopathological damage and the mitochondria ultrastructure injury were partially improved in the CIRI rats after ICCB treatment. Western blotting analysis indicated that ICCB significantly decreased the expression of Bax, caspase-9, caspase-3 and Cyto-Cyt C protein levels while increasing the expression of Bcl-2 and Mito-Cyt C protein levels. CONCLUSION: The ICCB protected against CIRI by suppressing the mitochondria-mediated apoptotic signalling pathway.

Emerging systemic drugs in the treatment of plaque psoriasis.

INTRODUCTION: Psoriasis is a common, chronic inflammatory skin condition that affects 2-3% of the US population and represents a large psychosocial burden for patients. Over the last decade, highly effective targeted therapies for psoriasis have been developed - namely, those targeting interleukin (IL)-17 and IL-23. The success of biologic agents targeting IL-17 and IL-23 underscores the importance of the IL-23/T helper (Th)17 cell axis in psoriasis pathogenesis. Oral small molecule drugs - such as Janus kinase (JAK) inhibitors, tyrosine kinase 2 (TYK2) inhibitors, and fumaric acid esters (FAEs) - are also being investigated for the treatment of psoriasis. AREAS COVERED: This article reviews systemic biologic and oral small molecule drugs currently undergoing clinical trials for the treatment of plaque psoriasis. EXPERT OPINION: Many patients with psoriasis have mild disease, and many with mild disease do not seek medical care for their condition. Many patients with mild disease could be adequately treated with topical treatments and phototherapy; however, adherence and feasibility have often been an issue with these treatment types. There seems to be limited room for development of novel biologics, as the existing ones are extraordinarily safe, effective, and convenient with few injections. Patients would prefer a safe, effective oral treatment; however, JAK inhibitors seem unlikely to fill this role completely.

A novel protein-based autologous topical serum for skin regeneration.

BACKGROUND: As skin ages, a functional decrement occurs. To avoid future vulnerability to dermatologic diseases, an optimal cutaneous regeneration is mandatory. Biological therapies based on blood-derived autologous proteins are gaining attention of scientists and dermatologists. OBJECTIVES: A novel 100% autologous topical serum has been developed using plasma rich in growth factors technology. The physicochemical characterization and the biologic potential of the novel formulation have been studied. METHODS: Rheological and mechanical properties and the biological capacity of the formulation were characterized. Human dermal fibroblast culture and 3D organotypic skin explants were used as in vitro and ex vivo cutaneous models, respectively. RESULTS: The autologous topical serum presented an optimal spreadability index and appropriate shear thinning behavior that allowed an easy handling and rapid integration within the cutaneous tissue. The formulation has a high growth factor load with the ability to progressively penetrate into the dermal/epidermal layers of the skin. It is biocompatible and promotes cell proliferation and chemotactic activity. The autologous topical serum promotes the biosynthetic activity of cells by the stimulation of collagen and hyaluronic acid expression. CONCLUSIONS: These findings present an in situ and easy to prepare autologous topical serum based on the patient's own blood with physicochemical and bioactive properties that may be used for skin regeneration purposes.

De-escalation of biological therapy in inflammatory bowel disease: Benefits and risks.

The treatment of inflammatory bowel disease (IBD) is often challenging. It has a vexing and waning course with frequent relapses, despite adequate maintenance therapy. Biological  agents have been available for the treatment of IBD for the last two decades, with impressive results. However, these drugs are costly and often have significant side-effects. Therefore, the benefit of aggressive treatment must be carefully balanced against the risk of serious adverse events. Despite good clinical outcomes, patients often request to discontinue the drugs because of cost and detrimental effects, especially the risk of malignancy. This review focuses on the benefits of biological treatment, strategies to de-escalate therapy, risk of relapse when these agents are discontinued and success with retreatment with the same or a similar biological agent.

First line of biological drugs in rheumatoid arthritis: a medication persistence analysis.

OBJECTIVES: To evaluate the persistence of biological drugs used as the first line of biological treatment in patients diagnosed with rheumatoid arthritis. The predictors associated with persistence have also been verified. METHODS: We evaluated a historical cohort composed of users of the Brazilian National Health System in the period between 2006 January and 2014 December. The endpoint was the medication persistence at 12 months. RESULTS: A population composed of 66,787 individuals started the first line of biological drug. Out of such individuals, 34,595 (51.80%) persisted in the treatment at 12 months. Abatacept was the drug that presented higher persistence, followed by golimumab, tocilizumab, etanercept, and adalimumab and, with lower persistence certolizumab and infliximab. Younger individuals, living in regions with higher social inequality by Gini coefficient, using certolizumab and infliximab in comparison with adalimumab presented a higher risk of non-persistence to treatment. Individuals from the Southeastern region were more persistent than Northeastern, Central-western, Northern and Southern regions. CONCLUSION: The medication persistence was different between biological drugs. The rigorous follow-up of patients, by a multidisciplinary team, is important to enable the development of strategies for the adequate use of such drugs.

Latex hypersensitivity to injection devices for biologic therapies in psoriasis patients.

An allergic reaction provoked by reexposure to an allergen or antigen is known as a type I or immediate hypersensitivity reaction. Latex allergy is a common cause of type I hypersensitivity reactions. Allergic responses to latex in psoriasis patients receiving frequent injections with biologic agents are not commonly reported in the literature. We report the case of a patient with a long history of psoriasis who developed an allergic response after exposure to injection devices that contained latex components while undergoing treatment with biologic agents.

A Biologically Based Approach to Acne and Rosacea.

Complementary and alternative medicine (CAM) therapies are increasing in popularity in the field of dermatology. Natural products and holistic approaches are in high demand among patients and research has begun to support their roles in acne and rosacea pathophysiology. In this article, commonly utilized biologically based complementary and alternative therapies for acne and rosacea are reviewed from an evidence-based perspective. Therapies discussed include vitamin C, nicotinamide, zinc, tea tree oil, green tea, resveratrol, curcumin, feverfew, licorice, chamomile, polypodium leucotomos, and nutrition-based approaches. J Drugs Dermatol. 2018;17(6):611-617.

Direct drug delivery in the treatment of steno-occlusive disease of the infra-inguinal arteries.

Peripheral Artery disease (PAD) is a cause of significant morbidity and mortality, affecting over 200 million people world-wide. Many exciting technologies have emerged to address the unique challenges endovascular specialists face when treating lesions in this vascular bed. One of the enduring challenges has been restenosis after initial intervention. Here we highlight a new technology, Direct drug delivery, to address this challenge and exciting prospects. Direct drug delivery constitutes delivering drug directly to the vessel wall through a needle with a micro-infusion catheter. This device has the potential to expand the types of therapies that can be delivered in a targeted fashion and allow endovascular specialists to individualize treatment for patients.

Switching from a biological therapy to another biologic agent in psoriatic patients: the experience of PsOMarche group.

BACKGROUND: Switching is a "hot" topic and the main reasons for switching prior biologic agent are for a primary failure, a secondary failure or drug intolerance, patient's dissatisfaction, physician decision. The aim of the study was to assess the optimization of the switching from a biologic agent to another. METHODS: Five Dermatological Units have participated to PsOMarche working group have studied thirty-eight patients affected moderate to severe chronic plaque psoriasis at time 0 (patient recruitment at time of switching from biological therapy to another), 8 weeks (T8), 16 weeks (T16). RESULTS: Twenty-eight males and 10 females were included in the study. At T0, 18 of 22 patients treated with etanercept had been switched to adalimumab and 4 to ustekinumab. Among 10 patients treated with adalimumab, 5 had been switched to ustekinumab, 2 to golimumab and 3 to certolizumab pegol. One patient treated with Infliximab and 5 patients treated with ustekinumab had been switched to adalimumab. Switching had been performed for primary inefficacy in 9 patients (23.6%) and a secondary failure was evidenced in 29 patients (73.4%). PASI75 was achieved in 53% and in 89.4% of patients after 8 weeks and 16 weeks of switching to the second biologic agent respectively; similarly, PsoDISK score significantly decreased at T8 and T16. CONCLUSIONS: The experience of PsOMarche group have shown that the switching to a biologic agent to another is a valuable treatment choice in patients with moderate to severe psoriasis experiencing a treatment failure with one biologic therapy, leading to a good improvement in skin disease and in patient's quality of life.

Biological Activities of Sesquiterpene Lactones Isolated from the Genus Centaurea L. (Asteraceae).

BACKGROUND: In recent years, a growing interest has developed in the field of biological activity of plant metabolites. Research in this area considering antimicrobial, antioxidant, cytotoxic, anti-inflammatory, and other properties, is currently expanding, reporting various species to possess such biological effects. Among them, Centaurea species are well known to be used in ethnomedicine. The Centaurea genus (Asteraceae) is represented by more than 500 species, mostly located in the Mediterranean region and Western Asia. METHODS: The current revision focuses on up-to-date literature on the isolation, structural elucidation and biological properties of sesquiterepene lactones from Centaurea species, regarding antimicrobial, antitumour, antiviral, anti-inflammatory and cytotoxic properties. The methods for extraction, isolation and identification are also pointed out and the bioactivity of lactones as purified compounds discussed. Several general ideas about the structural requirements for activity, based on the in vitro bioassays and the in silico prediction of their ADME properties are discussed. RESULTS: Investigations of chemical analyses and biological potential exhibited that flavonoids and sesquiterpene lactones, in particular germacranolides, eudesmanolides, elemanolides, and guaianolides, are compounds responsible for the biological potential of plants. Sesquiterpene lactones represent a group of compounds responsible for the medicinal characteristics of Centaurea species. DISCUSSION: Investigation of structure-activity relationships of all data helps the understanding of the bioactivity resulting from chemical aspects. All activities are discussed profoundly, paying special attention to molecular mechanisms involved in the implication of the health-beneficial effects of these compounds and in order to point them out as candidates for new drug discovery, and as safe natural agents.

Silkworm pupae oil exerts hypercholesterolemic and antioxidant effects in high-cholesterol diet-fed rats.

BACKGROUND: Silkworm pupae is a good resource of edible oil that is especially rich in unsaturated fatty acids and is considered to be an excellent dietary supplement for hyperlipidemia. RESULTS: Groups fed a high-cholesterol diet (HCD) with silkworm pupae oil (SPO) supplementation (1, 2, or 4 mL kg-1 day-1 ) orally had significantly lower levels of serum total cholesterol (P < 0.05) and low-density lipoprotein cholesterol (P < 0.05) compared to the HCD group. With regard to antioxidant parameters, except for levels of glutathione peroxidase (GSH-Px) in the liver, 2 and 4 mL kg-1 day-1 of SPO supplementation leaded to higher total antioxidant capacity (P < 0.05), superoxide dismutase (P < 0.05) and GSH-Px levels (P < 0.05), as well as lower malondialdehyde levels (P < 0.05), both in serum and liver compared to the HCD group. CONCLUSION: The results of the present study indicate that supplementation with SPO can improve lipid profiles and alleviate oxidative stress in high-cholesterol diet-fed rats. © 2016 Society of Chemical Industry.

Haematological, biochemical and histopathological aspects of Hericium erinaceus ingestion in a rodent model: A sub-chronic toxicological assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Hericium erinaceus is a culinary-medicinal mushroom and has a long history of usage in traditional Chinese medicine as a tonic for stomach disorders, ulcers and gastrointestinal ailments. AIM OF THE STUDY: The present investigation was aimed to evaluate the potential toxic effects of the aqueous extract from the fruiting bodies of H. erinaceus in rats by a sub-chronic oral toxicity study. MATERIALS AND METHODS: In this sub-chronic toxicity study, rats were orally administered with the aqueous extract of H. erinaceus (HEAE) at doses of 250, 500 and 1000mg/kg body weight (b.w.) for 90 days. Body weights were recorded on a weekly basis and general behavioural changes were observed. The blood samples were subjected to haematological, biochemical, serum electrolyte, and antioxidant enzyme estimations. The rats were sacrificed and organs were processed and examined for histopathological changes. RESULTS: No mortality or morbidity was observed in all the treated and control rats. The results showed that the oral administration of HEAE daily at three different doses for 90 days had no adverse effect on the general behaviour, body weight, haematology, clinical biochemistry, and relative organ weights. Histopathological examination at the end of the study showed normal architecture except for few non-treatment related histopathological changes observed in liver, heart and spleen. CONCLUSION: The results of this sub-chronic toxicity study provides evidence that oral administration of HEAE is safe up to 1000mg/kg and H. erinaceus consumption is relatively non-toxic.

Nutraceuticals and Bioactive Components from Fish for Dyslipidemia and Cardiovascular Risk Reduction.

Cardiovascular disease remains the most common health problem in developed countries, and residual risk after implementing all current therapies is still high. Permanent changes in lifestyle may be hard to achieve and people may not always be motivated enough to make the recommended modifications. Emerging research has explored the application of natural food-based strategies in disease management. In recent years, much focus has been placed on the beneficial effects of fish consumption. Many of the positive effects of fish consumption on dyslipidemia and heart diseases have been attributed to n-3 polyunsaturated fatty acids (n-3 PUFAs, i.e., EPA and DHA); however, fish is also an excellent source of protein and, recently, fish protein hydrolysates containing bioactive peptides have shown promising activities for the prevention/management of cardiovascular disease and associated health complications. The present review will focus on n-3 PUFAs and bioactive peptides effects on cardiovascular disease risk factors. Moreover, since considerable controversy exists regarding the association between n-3 PUFAs and major cardiovascular endpoints, we have also reviewed the main clinical trials supporting or not this association.

Benefits of Preventive Administration of Chlorella sp. on Visceral Pain and Cystitis Induced by a Single Administration of Cyclophosphamide in Female Wistar Rat.

Chlorella sp. is a green microalgae containing nutrients, vitamins, minerals, and chlorophyll. In some communities, Chlorella sp. is a traditional medicinal plant used for the management of inflammation-related diseases. In a rat model, ROQUETTE Chlorella sp. (RCs) benefits were investigated on visceral pain and associated inflammatory parameters related to cystitis both induced by cyclophosphamide (CYP). RCs was orally administered every day from day 1-16 (250 and 500 mg/kg body weight). Six hours after an intraperitoneal injection of 200 mg/kg body weight of CYP, body temperature, general behavior, food intake, and body weight were recorded. Twenty-four hours after CYP injection, rats were tested in two behavioral tests, an open field and the aversive light stimulus avoidance conditioning test, to evaluate the influence of pain on general activity and learning ability of rats. After euthanasia, bladders were weighed, their thickness was scored, and the urinary hemoglobin was measured. RCs orally administered at the two dosages significantly reduced visceral pain and associated inflammatory parameters related to cystitis both induced by CYP injection, and improved rat behavior. To conclude, RCs demonstrated beneficial effects against visceral pain and cystitis.

Cordyceps militaris fruit body extract ameliorates membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway.

Membranous glomerulonephritis (MGN) is a common pathogenesis of nephritic syndrome in adult patients. Nuclear factor kappa B (NF-κB) serves as the main transcription factor for the inflammatory response mediated nephropathy. Cordyceps militaris, containing various pharmacological components, has been used as a kind of crude drug and folk tonic food for improving immunity and reducing inflammation. The current study aims to investigate the renoprotective activity of Cordyceps militaris aqueous extract (CM) in the cationic bovine serum albumin (C-BSA)-induced rat model of membranous glomerulonephritis. Significant renal dysfunction was observed in MGN rats; comparatively, 4-week CM administration strongly decreased the levels of 24 h urine protein, total cholesterol, triglyceride, blood urea nitrogen and serum creatinine, and increased the levels of serum albumin and total serum protein. Strikingly, recovery of the kidney histological architecture was noted in CM-treated MGN rats. A significant improvement in the glutathione peroxidase and superoxide dismutase levels, and a reduced malondialdehyde concentration were observed in the serum and kidney of CM-treated rats. Altered levels of inflammatory cytokines including interleukins, monocyte chemoattractant protein-1, intercellular adhesion molecule 1, vascular adhesion molecule 1, tumor necrosis factor-α, 6-keto-prostaglandin F1α, and nuclear transcriptional factor subunit NF-κB p65 reverted to normal levels upon treatment with CM. The present data suggest that CM protects rats against membranous glomerulonephritis via the normalization of NF-κB activity, thereby inhibiting oxidative damage and reducing inflammatory cytokine levels, which further provide experimental evidence in support of the clinical use of CM as an effective renoprotective agent.

Systemic Therapy for Psoriasis and the Risk of Herpes Zoster: A 500,000 Person-year Study.

IMPORTANCE: The risk for herpes zoster (HZ) in patients with psoriasis treated with biologic medications or other systemic treatments has been given little attention to date. OBJECTIVE: To describe the risk for HZ in patients with psoriasis and its relation to treatment. DESIGN, SETTING, AND PARTICIPANTS: A cohort study was performed using the administrative database of Clalit Health Services, the largest public health care provider organization in Israel, in the setting of general community clinics, primary care and referral centers, and ambulatory and hospitalized care. We extracted information for all patients who received a psoriasis diagnosis from January 2002 to June 2013. Follow-up was conducted until the end of July 2013. The study included 95,941 patients with psoriasis in the analysis, with 522,616 person-years of follow-up. Incidence of HZ events was calculated for each systemic antipsoriatic medication provided, during a follow-up period of 11 years and 7 months. We used a generalized estimating equation Poisson regression model to examine the effect of each systemic treatment for psoriasis on HZ incidence, adjusting for age, sex, psoriasis severity, Charlson comorbidity index, steroid treatment, and socioeconomic status. MAIN OUTCOMES AND MEASURES: Incidence of HZ associated with systemic therapies. RESULTS: In a multivariate analysis, it was observed that treatment with phototherapy (rate ratio [RR], 1.09 [95% CI, 0.62-1.93]; P = .99), methotrexate (RR, 0.98 [95% CI, 0.78-1.23]; P = .83), cyclosporine (RR, 1.16 [95% CI, 0.48-2.80]; P = .49), and biologic medications as a single agent (RR, 2.67 [95% CI, 0.69-10.3]; P = .14) was not associated with HZ. The use of combination treatment with biologic medications and methotrexate was significantly associated with an increased incidence of HZ (RR, 1.66 [95% CI, 1.08-2.57]; P = .02). The use of acitritin was associated with decreased incidence of HZ (RR, 0.69 [95% CI, 0.49-0.97]; P = .004). CONCLUSIONS AND RELEVANCE: Physicians may need to consider offering an HZ preventive vaccine to patients receiving combination treatment with biologic medications and methotrexate, particularly if they have additional risk factors for HZ.

[Preliminary study on substitution of Antelope Horn in Danqi Piantan capsule with artificial bezoar].

To study the protective effect of Danqi Piantan capsule ( DPC) and its antelope horn substitution (DPCAS) on the cerebral ischemia, in order to preliminary study the possibility of replacing antelope horn with artificial bezoar. In this study, the left middle cerebral artery occlusion (MCAO) was adopted. Totally 150 SD rats were randomly divided into 5 groups: the sham operation group, the model group, the Danqi Piantan capsule (DPC) group (0.246 g x kg(-1) x d(-1)), the Danqi Piantan capsule without antelope horn (DPCRA) group (0.246 g x kg(-1) x d(-1)), the Danqi Piantan capsule without antelope horn and with double artificial bezoar (DPCDB) group (0.246 g x kg(-1) x d(-1)). The MCAO model was prepared 1 h later after the administration on the 5th day. At 24 h after the operation, the inner canthus blood was collected to determine the serum superoxide dismutase (SOD) activity and the endothelin (ET) content. At 72 h after the operation, the cerebral infarct size and the cerebral index were determined by TTC-staining. The fluorescent quantitative PCR method was used to detect brain Bcl-2, Caspase-3, IL-1ß, P-selectin, E-selectin, ICAM-1 mRNA expressions. The mmunohistochemical method was used to detect ICAM-1, IL-1ß, TNF-α, IL-6 expressions in ischemic penumbra. According to the results, compared with the model group, DPCDB and DPC groups showed almost consistent results, indicating both of the two group can significantly improved cerebral infarction index and cerebral index (P < 0.05), increase the serum SOD activity (P < 0.05), decrease the serum ET level and Caspase-3 expression, IL-1ß, P-selectin, E-selectin, ICAM-1 mRNA expressions in brain tissues (P < 0.05) and expressions of ICAM-1, IL-1,6, TNF-α, IL-6 positive cells in ischemic penumbra (P < 0.05) and increase the Bcl-2 expression (P < 0.05). The DPCRA group showed much lower impacts on indexes than DPCDB and DPC groups. This suggests that DPCDB and DPC reveal similar efficacies and antelope horn in Danqi Piantan capsule can be substitutes by artificial bezoar.

Use of biologic agents in combination with other therapies for the treatment of psoriasis.

Psoriasis is a chronic inflammatory skin disorder, which is associated with a significant negative impact on a patient's quality of life. Traditional therapies for psoriasis are often not able to meet desired treatment goals, and high-dose and/or long-term use is associated with toxicities that can result in end-organ damage. An improved understanding of the involvement of cytokines in the etiology of psoriasis has led to the development of biologic agents targeting tumor necrosis factor (TNF)-α and interleukins (ILs)-12/23. While biologic agents have improved treatment outcomes, they are not effective in all individuals with psoriasis. The combination of biologic agents with traditional therapies may provide improved therapeutic options for patients who inadequately respond to a single drug or when efficacy may be increased with supplementation of another treatment. In addition, combination therapy may reduce safety concerns and cumulative toxicity, as lower doses of individual agents may be efficacious when used together. This article reviews the current evidence available on the efficacy and safety of combining biologic agents with systemic therapies (methotrexate, cyclosporine, or retinoids) or with phototherapy, and the combination of biologic agents themselves. Guidance is provided to help physicians identify situations and the characteristics of patients who would benefit from combination therapy with a biologic agent. Finally, the potential clinical impact of biologic therapies in development (e.g., those targeting IL-17A, IL-17RA, or IL-23 alone) is analyzed.

Mycelial fermentation characteristics and anti-fatigue activities of a Chinese caterpillar fungus, Ophiocordyceps sinensis strain Cs-HK1 (Ascomycetes).

Mycelial fermentation of an Ophiocordyceps sinensis strain Cs-HK1 was carried out in various volumes of stirred-tank fermenters from 1.6-L and 15-L laboratory scale to 2000-L industrial scale. The mycelial growth in most fermenters had a higher rate, due probably to more efficient oxygen supply, than in shake-flasks. The mycelial fermentation was successfully scaled up to 2000-L industrial fermenters, achieving 30 g/L maximum biomass in 5 days. The Cs-HK1 mycelia formed hairy and fluffy pellets in the fermentation medium and the mycelial broth exhibited pseudoplastic rheology following the power law, with the flow behavior index n decreasing from 0.5 to 0.3, and the flow consistency K and the apparent viscosity µα increasing with time and biomass concentration. The mycelial broth containing biomass and extracellular products harvested from 2000-L fermenters was tested for anti-fatigue activities in forced animal swimming experiments. The mycelium hot water extract showed the most significant effects, increasing the swimming endurance of mice up to 100%, and also increasing the glycogen levels and reducing the lactic acid and blood urea nitrogen levels significantly. The results demonstrated the feasibility of Cs-HK1 mycelial fermentation for large-scale production of bioactive and medicinal materials.